Adenocarcinoma Cancer Cell Lines Research Articles

IN VITRO CYTOTOXIC ACTIVITIES OF PLATINUM(II) COMPLEXES CONTAINING 1H-BENZO[d]IMIDAZOLE AND 1H-1,3-DIAZOLE DERIVATIVES

Objective: This study aimed to synthesize and evaluate the cytotoxic activities of four platinum(II) complexes with 2-substituted or nonsubstituted 1H-benzo[d]imidazole and 1H-1,3-diazole derivatives as carrier ligands (L1-L4), which may have potent cytotoxic activity and low side effects. Material and Method: K1-K4 complexes were synthesized by heating and mixing K2PtCl4 and the appropriate L1-L4. The chemical structures of K1-K4 were elucidated by Infrared and 1H Nuclear Magnetic Resonance spectroscopic methods. In vitro, cytotoxic effects of K1-K4 complexes against prostate (DU-145), endometrial adenocarcinoma (Ishikawa), and breast cancer (MCF-7) cell lines were tested by the MTT method. Result and Discussion: According to the IC50 values of the tested cell lines, K1 and K2 derivatives bearing unsubstituted 1H-benzo[d]imidazole (L1) and 1H-1,3-diazole (L2) were found to be the most effective compounds among these synthesized complexes.

IN VITRO CYTOTOXIC ACTIVITIES OF PLATINUM(II) COMPLEXES CONTAINING 1H-BENZO[d]IMIDAZOLE AND 1H-1,3-DIAZOLE DERIVATIVES

Objective: This study aimed to synthesize and evaluate the cytotoxic activities of four platinum(II) complexes with 2-substituted or nonsubstituted 1H-benzo[d]imidazole and 1H-1,3-diazole derivatives as carrier ligands (L1-L4), which may have potent cytotoxic activity and low side effects. Material and Method: K1-K4 complexes were synthesized by heating and mixing K2PtCl4 and the appropriate L1-L4. The chemical structures of K1-K4 were elucidated by Infrared and 1H Nuclear Magnetic Resonance spectroscopic methods. In vitro, cytotoxic effects of K1-K4 complexes against prostate (DU-145), endometrial adenocarcinoma (Ishikawa), and breast cancer (MCF-7) cell lines were tested by the MTT method. Result and Discussion: According to the IC50 values of the tested cell lines, K1 and K2 derivatives bearing unsubstituted 1H-benzo[d]imidazole (L1) and 1H-1,3-diazole (L2) were found to be the most effective compounds among these synthesized complexes.

Anti-cancer activity of NTAX-44 (bioprocessed arsenic trioxide) on lung cancer.

e20573 Background: In contemporary allopathic medicine, intravenous administration of Arsenic trioxide is extensively investigated for its diverse applications in cancer treatment. However, the associated adverse effects demand exploration of alternative formulations. In present study, we propose the patented green technology-based compound “oral Arsenic Trioxide” (NTAX-44), in its unique form that can be administered orally, thereby reduces cost of treatment. This product presenting itself as a promising candidate for cancer therapy. Despite the ethnopharmacological uses of arsenicals in medicine, comprehensive understanding of their safety and efficacy remains limited. Thus, present study is proposed to investigate anticancer potential of NTAX-44 in lung adenocarcinoma cancer cell line A549. Methods: The effect of oral NTAX-44 was assessed on the viability of cell lines grown as 2D monolayers by MTS assay and 3D multicellular spheroid (MCS) model. Anti-metastatic potential of NTAX-44 was studied by using migration and colony formation assay while, expression of PD-L1 in A549 cell line treated with Arsenic Trioxide was checked by flow cytometry. The anti-metastatic capacity and cytocompatibility testing of Arsenic Trioxide was evaluated by in ovo chick embryo yolk sac membrane (YSM) angiogenesis assay and MTS assay using PBMCs respectively. Results: NTAX-44 is found to be effective to inhibit viability of A549 cell line (IC50 21.47±1.7 μg/ml for 48 hr and 14.65±0.92 for 72 hr of treatment); exhibiting its anti-proliferative activity. The A549 spheroids showed comparatively more resistance with loss of viability at higher concentration (50 and 100 µg/ml). Statistically significant decrease in scratch repair rate was observed at 24 hr and 72 hr of treatment and showing anti-migratory activity in A549 cells. In colony formation assay, complete inhibition of the colonization of A549 cells was observed after 48 hr of treatment; the survival fraction identified as 0%. NTAX-44 at 25µg/ml concentration inhibited PD-L1 expression in A549 cells, suggesting its potential to decrease expression of PD-L1 on tumor cells resulting in reversal of immune suppressive tumor microenvironment. Treatment of YSM with NTAX-44 resulted in approximately 40% inhibition in formation of quaternary blood vessels comparable to Bevacizumab (Avastin®). This significant anti-angiogenic potential is suggestive of its in vivo anti-metastatic effect. Notably, cytocompatibility testing of NTAX-44 at concentrations up to 200μg/ml was well-tolerated in PBMC cells emphasizing its favourable biocompatibility profile, providing crucial insights into its safety. Conclusions: Inhibitory effect of NTAX-44 on cell proliferation serves as a noteworthy attribute in context of its potential therapeutic utility against lung cancer. Its cytocompatibility further indicates application of arsenic trioxide as a candidate for clinical application.

Bcl-2 dependent modulation of Hippo pathway in cancer cells

IntroductionBcl-2 and Bcl-xL are the most studied anti-apoptotic members of Bcl-2 family proteins. We previously characterized both of them, not only for their role in regulating apoptosis and resistance to therapy in cancer cells, but also for their non-canonical functions, mainly including promotion of cancer progression, metastatization, angiogenesis, and involvement in the crosstalk among cancer cells and components of the tumor microenvironment. Our goal was to identify transcriptional signature and novel cellular pathways specifically modulated by Bcl-2.MethodsWe performed RNAseq analysis of siRNA-mediated transient knockdown of Bcl-2 or Bcl-xL in human melanoma cells and gene ontology analysis to identify a specific Bcl-2 transcriptional signature. Expression of genes modulated by Bcl-2 and associated to Hippo pathway were validated in human melanoma, breast adenocarcinoma and non-small cell lung cancer cell lines by qRT-PCR. Western blotting analysis were performed to analyse protein expression of upstream regulators of YAP and in relation to different level of Bcl-2 protein. The effects of YAP silencing in Bcl-2 overexpressing cancer cells were evaluated in migration and cell viability assays in relation to different stiffness conditions. In vitro wound healing assays and co-cultures were used to evaluate cancer-specific Bcl-2 ability to activate fibroblasts.ResultsWe demonstrated the Bcl-2-dependent modulation of Hippo Pathway in cancer cell lines from different tumor types by acting on upstream YAP regulators. YAP inhibition abolished the ability of Bcl-2 to increase tumor cell migration and proliferation on high stiffness condition of culture, to stimulate in vitro fibroblasts migration and to induce fibroblasts activation.ConclusionsWe discovered that Bcl-2 regulates the Hippo pathway in different tumor types, promoting cell migration, adaptation to higher stiffness culture condition and fibroblast activation. Our data indicate that Bcl-2 inhibitors should be further investigated to counteract cancer-promoting mechanisms.

Fabrication and Characterization of Colorectal Cancer Organoids from SW1222 Cell Line in Ultrashort Self-Assembling Peptide Matrix.

Ultrashort self-assembling peptides (SAPs) can spontaneously form nanofibers that resemble the extracellular matrix. These fibers allow the formation of hydrogels that are biocompatible, biodegradable, and non-immunogenic. We have previously proven that SAPs, when biofunctionalized with protein-derived motifs, can mimic the extracellular matrix characteristics that support colorectal organoid formation. These biofunctional peptide hydrogels retain the original parent peptide's mechanical properties, tunability, and printability while incorporating cues that allow cell-matrix interactions to increase cell adhesion. This paper presents the protocols needed to evaluate and characterize the effects of various biofunctional peptide hydrogels on cell adhesion and lumen formation using an adenocarcinoma cancer cell line able to form colorectal cancer organoids cost-effectively. These protocols will help evaluate biofunctional peptide hydrogel effects on cell adhesion and luminal formation using immunostaining and fluorescence image analysis. The cell line used in this study has been previously utilized for generating organoids in animal-derived matrices.

Genotoxic and antiproliferative properties of Endopleura uchi bark aqueous extract

ABSTRACT The bark extract from Endopleura uchi has been widely used in traditional medicine to treat gynecological-related disorders, diabetes, and dyslipidemias albeit without scientific proof. In addition, E. uchi bark extract safety, especially regarding mutagenic activities, is not known. The aim of this study was to determine the chemical composition, antitumor, and toxicological parameters attributed to an E. uchi bark aqueous extract. The phytochemical constitution was assessed by colorimetric and chromatographic analyzes. The antiproliferative effect was determined using sulforhodamine B (SRB) assay using 4 cancer cell lines. Cytotoxic and genotoxic activities were assessed utilizing MTT and comet assays, respectively, while mutagenicity was determined through micronucleus and Salmonella/microsome assays. The chromatographic analysis detected predominantly the presence of gallic acid and isoquercitrin. The antiproliferative effect was more pronounced in human colon adenocarcinoma (HT-29) and human breast cancer (MCF-7) cell lines. In the MTT assay, the extract presented an IC50 = 39.1 µg/ml and exhibited genotoxic (comet assay) and mutagenic (micronucleus test) activities at 20 and 40 µg/ml in mouse fibroblast cell line (L929) and mutagenicity in the TA102 and TA97a strains in the absence of S9 mix. Data demonstrated that E. uchi bark possesses bioactive compounds which exert cytotoxic and genotoxic effects that might be associated with its antitumor potential. Therefore, E. uchi bark aqueous extract consumption needs to be approached with caution in therapeutic applications.

Liposome-encapsulated progesterone efficiently suppresses B-lineage cell proliferation

Progesterone suppresses several ancient pathways in a concentration-dependent manner. Based on these characteristics, progesterone is considered a candidate anticancer drug. However, the concentration of progesterone used for therapy should be higher than the physiological concentration, which makes it difficult to develop progesterone-based anticancer drugs. We previously developed liposome-encapsulated progesterone (Lipo-P4) with enhanced anticancer effects, which strongly suppressed triple-negative breast cancer cell proliferation in humanized mice. In this study, we aimed to clarify whether Lipo-P4 effectively suppresses the proliferation of B-lineage cancer cells. We selected six B-cell lymphoma and two myeloma cell lines, and analyzed their surface markers using flow cytometry. Next, we prepared liposome-encapsulated progesterone and examined its effect on cell proliferation in these B-lineage cancer cells, three ovarian clear cell carcinoma cell lines, two prostate carcinoma cell lines, and one triple-negative breast cancer adenocarcinoma cell line. Lipo-P4 suppressed the proliferation of all cancer cell lines. All B-lineage cell lines, except for the HT line, were more susceptible than the other cell types, regardless of the expression of differentiation markers. Empty liposomes did not suppress cell proliferation. These results suggest that progesterone encapsulated in liposomes efficiently inhibits the proliferation of B-lineage cells and may become an anticancer drug candidate for B-lineage cancers.

Abstract 3147: DXC025, a novel anti-MUC1/EGFR bispecific antibody-tubulysin conjugate with a function linker, exhibits potent anti-tumor efficacy

Abstract Antibody-drug conjugates (ADCs) have become a promised drug class in cancer therapy. Armed with three main components-an antibody, a linker molecule, and a cytotoxic agent (“payload”), plus sites of the antibody conjugation and the distribution of tumor-associate antigens, nowadays ADCs have proved the unique ability of the precision of targeted therapy, a great leap forward from traditional chemotherapeutic approaches that cause widespread effects without specificity. Both epidermal growth factor receptor (EGFR) and mucin 1 (MUC1) are tumor-associated antigens (TAA) that are co-expressed in many solid tumors, such as, colon cancer, non-small cell lung cancer (NSCLC), esophageal cancer, epidermal cancer, and pancreatic cancer. In particular, MUC1, a glycoprotein essential for the formation of the epithelial mucous barrier, is hypoglycosylated and dimerizes with EGFR, a potent oncoprotein, in transformed cells. For our anti-Muc1 ADC clinical program, for treatment of colon and pancreatic cancers, it was found out that the highly glycosylated transmembrane Muc1 had much more turning over rates on the luminal surface of epithelial cells. Here, we first designed and generated bispecific Fab/scFv antibodies targeting both MUC1 and EGFR, using the knob-into-hole technology. The addition of the affinity- and internalization-optimized anti-EGFR arm to the other single Muc1 arm was aimed to broaden tumor selectivity and to reduce on-target toxicity, for the treatment of gastrointestinal tumors in comparison to individual full IgG1-ADC, either EGFR or Muc1-ADC. Indeed, many of generated anti- MUC1/EGFR bispecific antibodies (BsAbs) showed strong binding affinity in MUC1modetateEGFRmodetate cells, in addition to both MUC1 and EGFR highly expressed cells. Internalization assays demonstrated that the BsAbs were endocytosed in tumor cells co-expressing EGFR and MUC1 more efficiently than monoclonal antibodies targeting MUC1. The selected BsAbs were subsequently conjugated with tubulysin B analogs with varieties of Tubulysin B analog payloads and function peptidyl spacer/linkers to generate bispecific ADC (DXC025) candidates. DXC025 candidates exhibited very potent cytotoxicity in vitro against epidermal cancer, lung adenocarcinoma, and pancreatic cancer cell lines with IC50 of single or tens digital pM. In in vivo cell-derived xenograft (CDX) models, DXC025 candidates demonstrated much superior efficacies of tumor growth inhibition in comparison with parental (monoclonal), either Muc1- or EGFR- ADC for the treatment of gastrointestinal tumors. These results indicated that the MUC1/EGFR-ADC (DXC025) would be a promising ADC candidate for targeted treatment of either Muc1- or EGFR-expressing gastrointestinal tumors. Citation Format: Xingyan Jiang, Junxiang Jia, Huihui Guo, Xiangfei Kong, Yongfang Xu, Sishi Ye, Yong Du, Zhicang Ye, Qikuang Cen, Lingli Zhang, Yongxiang Chen, Gaituo Chen, Lu Bai, Yunxia Zheng, Wei Zheng, Jun Zheng, Juan Wang, Wenjun Li, Yuanyuan Huang, Linyao Zhao, Yifang Xu, Mengmeng Liu, Binbin Chen, Meng Dai, Miaomiao Chen, Zhixiang Guo, Qingliang Yang, Robert Y. Zhao. DXC025, a novel anti-MUC1/EGFR bispecific antibody-tubulysin conjugate with a function linker, exhibits potent anti-tumor efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3147.

Anticancer, Antioxidant, Antimicrobial Activities, and HPLC Analysis of Alcoholic Extracts of Parthenocissus quinquefolia L. Plant Collected from Çanakkale

This study aimed to contribute to revealing the health effects of the Parthenocissus quinquefolia L. (PQ) plant by examining the biological activities of various extracts of the plant. An ethnobotanical important medicinal plant, PQ belongs to the Vine family (Vitaceae) and is known for its medicinal uses. Herein, fruit and leaf alcoholic extracts of the plant exhibited anticancer activity on triple negative breast cancer (TNBC) cell lines, estrogen receptor positive (ER+) (MCF-7), and human colon adenocarcinoma (HT-29) cancer cell lines. Furthermore, fruit methanol extracts displayed strong radical scavenging activity with low IC50 values such as 0.51 mg/mL, 0.80 mg/mL, 0.84 mg/mL, and 1.45 mg/mL. The highest TEAC values (18.72 mM Trolox/mg, 9.90 mM Trolox/mg, and 8.41 mM Trolox/mg) were calculated for the extracts of red leaves. The antifungal activity was determined against Candida albicans as fungal pathogen. The cell apoptosis with methanol extract was obtained between 20 µg/mL and 70 µg/mL for 48 h and 72 h treatments by Hoechst 33258 staining of nuclei under a fluorescence microscopy. HPLC analysis was performed for methanol extracts to determine major bioactive components. Consequently, this plant extracts may guide to new strategies and may be uses in medicinal applications for further investigations.

New Imidazo[4,5‐c]pyridine‐piperidine Hybrids as Potential Anti‐cancer Agents and In‐Silico Studies

AbstractDesign and synthesis of a series of novel hybrid molecules that combine Imidazo[4,5‐c] pyridines with piperdines are presented in this paper. Total 17 derivatives were meticulously synthesized and characterized using 1H NMR, 13C NMR, MS and elemental analysis techniques. The in vitroanticancer activities are estimated by verifying their effectiveness against the MCF‐7 human breast adenocarcinoma and A549 lung cancer cell line, with cisplatin and doxorubicin serving as reference drugs. Several of these compounds demonstrated significant potential, displaying IC50 values within the range of 12.26–84.5 μM for A549, and 13.37–69.82 μM for MCF‐7. Notably, compound 11 bis found to be more potent than the standard drug cisplatin with an IC50 of 12.26±0.8 μM against A549 cells, while compound 11 d exhibited highest inhibition with an IC50 of 13.37±0.4 μM against MCF‐7 cells. Although its effectiveness was moderately lower when compared to doxorubicin, it still retained substantial anticancer activity. Molecular docking studies were performed to decouple the binding affinity and ligand interactions of the compounds with the estrogen receptor alpha (ERα) (PDB ID: 3ERT). The pharmacokinetic evaluation revealed favourable drug‐likeness properties for all the molecules, suggesting their potential as therapeutic agents.

Characterization and Evaluation of Nano-niosomes Encapsulating Docetaxel against Human Breast, Pancreatic, and Pulmonary Adenocarcinoma Cancer Cell Lines.

Docetaxel (DXL) is an antineoplastic agent for cancer treatment, the therapeutic efficiency of which is limited due to low solubility, hydrophobicity, and tissue specificity. In this study, nano-niosomes were introduced for improving therapeutic index of DXL. In this experimental study, two nano-niosomes were synthesized using Span 20® and Span 80® and a thin film hydration method with DXL loading (DXL-Span20 and DXL-Span80). Characterization, in-vitro cytotoxicity and bioavailability of the nano-niosomes was also evaluated via in-vivo experiments. DXL-Span20 and DXL-Span80 have vesicles size in a range of 84-90 nm and negative zeta potentials. DXL entrapment efficiencies were obtained as 69.6 and 74.0% for DXL-Span20 and DXL-Span80, respectively; with an in-vitro sustained release patterns. Cytotoxicity assays were performed against MDA-MB-231, Calu-6, and AsPC-1 cell lines, and the results indicated that DXL loading into nano-niosomes led to decrement in values of half-maximal inhibitory concentration (IC50) at least 2.5 times and at most 6.5 times, compared to free DXL. Moreover, the rat blood bioavailability of DXL after intraperitoneal administration and the pharmacokinetic parameters indicated higher DXL plasma level and the higher effectiveness of DXL-Span80 compared to DXL-Span20. Carrying DXL by the nano-niosomes led to enhanced cytotoxicity (and lower IC50 values) and higher efficacy with enhanced pharmacokinetic parameters.

Development of new cobalt, copper, and zinc complexes of Schiff-base ligands as prospective chemotherapeutic agents

Fluorobenzaldehyde was converted into new, bidentate Schiff-base ligands with nitrogen and sulphur donor sites in two steps. The first step proceeds via Knoevenagel condensation; the product obtained was treated with thiosemicarbazide to yield the ligand L1. The Schiff-base ligand, L2, was synthesized by treating L1 with 4-chlorobenzylchloride in a basic medium. Co (II), Cu (II), and Zn (II) complexes were synthesized with the ligands L1 and L2. All these complexes were characterized by FTIR, UV–Vis, NMR spectroscopy, ESI-mass spectral analysis, magnetic moment, molar conductance, thermal, powder XRD, and electrochemical studies. From these studies, the molecular formulae of the complexes were found to be [M(L)2Cl2], where M = Co (II), Cu (II) and Zn (II) and L = L1 or L2 based on the ligand used in the synthesis. The synthesized complexes were observed to have a high spin and distorted octahedral geometry and were non-electrolytic. The UV absorption titrimetric analysis confirmed that these complexes would bind strongly to CT-DNA through the intercalative mode. The electrophorograms supported the statement that Cu (II) complexes could effectively catalyze the hydrolytic cleavage of CT-DNA and can be considered potent metallonuclease agents. The DPPH assay determined the antioxidant properties of these complexes, and the cupric complexes were observed to possess better antioxidant properties than the standard used ascorbic acid. The cell viability analysis of these complexes showed an elevated control of proliferation against a human breast adenocarcinoma (MCF-7) cancer cell line compared to a human cervical carcinoma (HeLa) cell line. The results exhibited by these compounds were compared with the standard drug, cisplatin. The binding affinity of the Cu (II) metal ion complex towards CT-DNA was high when compared to Co (II) and Zn (II) metal ions. These results are in line with the cytotoxicity studies. Molecular docking studies also hold up the experimental data. Cu (II) complexes using ligand L2 show higher efficiency than those with ligand L1 in all biological assays and can be considered a potent DNA-targeting drug.

Green synthesis of titanium nanoparticles using a sustainable microalgal metabolite solution for potential biotechnological activities

AbstractIn this study, green synthesis of titanium nanoparticles using liquids metabolites of microalgae, Porphyridium cruentum, was performed to evaluate potential biotechnological activity. The rising rates of multidrug‐resistant bacteria and the number of cancer patients are driving the search for novel antimicrobial and anticancer agents to combat this threat. In recent years, with the increasing number of studies, nanomaterials are starting to be better understood and are emerging as a solution to this problem. Especially, green synthesized nanoparticles with anticancer, antioxidant, and antimicrobial activities have potential in biomedical applications because of their eco‐friendly and biocompatible nature. Scanning electron microscopy (SEM) images revealed that spherical shaped Ti‐NPs' size ranged from 62 to 133 nm. This study aimed to assess the effectiveness of antibacterial activity of Ti‐NPs and chitosan‐coated Ti‐NPs against Escherichia coli and Staphylococcus aureus using disc diffusion assay. It demonstrated the concentration‐dependent cytotoxic effect of Ti‐NPs of human prostate adenocarcinoma (PC‐3), human alveolar adenocarcinoma (A549), and human mammary gland adenocarcinoma (MDA‐MB) cancer cell lines. This present study shows promising outcomes for possible future applications of synthesized Ti‐NPs as a novel antibacterial and cytotoxic agent for biomedical applications such as drug delivery, biosensor, and hyperthermia.

Investigation of in vitro antimicrobial, antioxidant and antiproliferative activities of Nostoc calcicola biosynthesized gold nanoparticles.

The cyanobacteria are the promising candidate for synthesizing gold nanoparticles (AuNPs), due to their ability to accumulate heavy metals from the cellular environment and additionally contain varied bioactive compounds as reducing and stabilizing agents. This study describes the N2-fixing cyanobacterium Nostoc calcicola-mediated bioreduction of AuNPs and the inherent antimicrobial, antioxidant, and antiproliferative activities in vitro. Biosynthesized Nc-AuNPs were characterized by spectral characterization techniques. The formation of AuNPs was physically confirmed by the colour change from pale green to dark violet. The UV-Vis analysis, further, proved the reduction in Nc-AuNPs with the cyanobacterium and showed a spectral peak at 527nm. FESEM-EDX images suggested the surface morphology of the NPs as spherical, cuboidal, and size between 20 and 140nm. The antimicrobial studies of Nc-AuNPs were carried out by agar-well diffusion method and MIC values against five pathogenic bacterial and two fungal strains were noted. The AuNPs exhibited potential antimicrobial activity against h-pathogenic bacteria with inhibitory zones ranging at 11-18mm; against fungi ranging at 13-17mm. Significant antioxidant potentialities were explored by a DPPH assay with an IC50 value of 55.97μg/ mL. Furthermore, in the anticancer efficacy assay, the Nc-AuNPs inhibited cellular proliferation in human breast adenocarcinoma and cervical cancer cell lines at IC50 concentration, 37.3μg/ml, and 44.5μg/ml, respectively. Conclusively, N. calcicola would be an excellent source for synthesizing stable colloidal AuNPs that had significant credibility as phycological (algal) nanomedicines as novel prodrugs with multiple bioactivities.

Abstract 5477: An investigation to study differential gene expression of lung cancer cells, tumor associated macrophages, and bone marrow derived mesenchymal stems cells in the tumor microenvironment

Abstract Cancer is a public health crisis affecting approximately 19.3 million globally, annually. Lung cancer has the highest percentage of incidence and is responsible for 27% of cancer-related deaths. The prevalence of lung cancer worldwide led us to investigate differential gene expression in lung adenocarcinoma and small cell lung cancer cell lines in comparison to a healthy lung cell line. We also investigated the effect of lung tumor microenvironment to bone marrow derived pluripotent mesenchymal stem cells (PMSC) and tumor associated macrophages. This research involved cancer and healthy cell line culture with appropriate medium. Whole transcriptomic and small non-coding RNA sequencing and analysis by Ingenuity Pathway Analysis (Qiagen, USA), Quantitative RT-PCR and ELISA assays. We further studied morphological changes and differential gene expression in extracellular vesicles(exosomes) isolated from the TAM and TME exposed PMCs by atomic force microscopy and RNA sequencing techniques. The results of our investigation showed differential gene expression and novel core canonical pathways in the lung cancer cells, TME exposed TAM, and PMSC. We also observed morphological changes in TME derived exosomes from TAM and PMSC. RNA sequencing results showed differential gene expression of both coding and non-coding RNAs including tRNA fragments. Thus, our findings of this investigation led to identification of multiple cancer related genes and small non-coding microRNA, long non-coding RNA, and tRNA fragments which will have potential diagnostic and therapeutic target value that demands further future research. Acknowledgement: This research is supported by a grant from US NIH-NIGMS- 5T34GM100831-08 and US-NIH Grant# U 54 MD007597-31-5959. Citation Format: Hirendra N. Banerjee, Joseph Hedley, Cheslsey Aurelus, Narendra Banerjee, Kuldeep Rawat, Quentin Reaves, Shennel Brown, Darla Gilmartin, Makieyah Liverman, Jazmine Cuffee, Elizabeth Cagle, Erik Armstrong, Brent Lake, Santosh Mandal, Somiranjan Ghosh, Stephen Beebe, Kamal Asadipour, Christopher Krauss, Santanu Bhattacharya, Tanmay Kulkarni, Zahidur Abedin. An investigation to study differential gene expression of lung cancer cells, tumor associated macrophages, and bone marrow derived mesenchymal stems cells in the tumor microenvironment. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5477.

Biogenic Synthesis of Cu-Mn Bimetallic Nanoparticles Using Pumpkin Seeds Extract and Their Characterization and Anticancer Efficacy

Cancer is a chronic, heterogeneous illness that progresses through a spectrum of devastating clinical manifestations and remains the 2nd leading contributor to global mortality. Current cancer therapeutics display various drawbacks that result in inefficient management. The present study is intended to evaluate the anticancer potential of Cu-Mn bimetallic NPs (CMBNPs) synthesized from pumpkin seed extract against colon adenocarcinoma cancer cell line (HT-29). The CMBNPs were biosynthesized by continuously stirring an aqueous solution of pumpkin seed extract with CuSO4 and manganese (II) acetate tetrahydrate until a dark green solution was obtained. The characteristic features of biogenic CMBNPs were assessed by UV-visible spectrophotometry (UV-vis), X-ray powder diffraction (XRD), energy-dispersive X-ray (EDX), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). A battery of biological assays, viz. neutral red uptake (NRU) assay, in vitro scratch assay, and comet assay, were performed for anticancer efficacy evaluation. The formation of spherical monodispersed bimetallic nanoparticles with an average size of 50 nm was recorded using TEM. We observed dose-dependent cytotoxicity of CMBNPs in the HT-29 cell line with an IC50 dose of 115.2 µg/mL. On the other hand, CMBNPs did not show significant cytotoxicity against normal cell lines (Vero cells). Furthermore, the treatment of CMBNPs inhibited the migration of cancer cells and caused DNA damage with a significant increase in comet tail length. The results showed substantial anticancer efficacy of CMBNPs against the studied cancer cell line. However, it is advocated that the current work be expanded to different in vitro cancer models so that an in vivo validation could be carried out in the most appropriate cancer model.

The Investigation of the Chemical Composition and Applicability of Gold Nanoparticles Synthesized with Amygdalus communis (Almond) Leaf Aqueous Extract as Antimicrobial and Anticancer Agents

The current work's main objective was to determine the chemical composition of Amygdalus communis (AC) leaf extract and examine the antibacterial and cytotoxic properties of biosynthesized gold nanoparticles (AuNPs). The chemical composition of AC leaf extract was determined using LC-ESI/MS/MS to detect compounds that may be responsible for the reducing, stabilizing, and capping steps in the synthesis of nanoparticles and their biological activities. The AC-AuNPs were spherical, with a particle size lower than 100 nm and a face-centered cubic structure. The EDX spectrum confirmed the formation of AuNPs and a negative zeta potential value (-27.7 mV) suggested their physicochemical stability. The in vitro cytotoxic efficacy of the AC-AuNPs against colorectal adenocarcinoma (Caco-2), glioma (U118), and ovarian (Skov-3) cancer cell lines and human dermal fibroblasts (HDFs) was evaluated by MTT assay. CaCo-2 cell proliferation was effectively inhibited by the AC-AuNPs at concentrations between 25 and 100 g mL-1. The AC-AuNPs exerted preeminent antimicrobial activity against Bacillus subtilis with an MIC of 0.02 μg/mL, whilst good activity was shown against Staphylococcus aureus bacteria and Candida albicans yeast with an MIC of 0.12 μg/mL. Ultimately, the results support the high antibacterial and anticancer potential of biosynthesized AuNPs from AC leaf extract.

Chemical Compositions and Experimental and Computational Modeling of the Anticancer Effects of Cnidocyte Venoms of Jellyfish Cassiopea andromeda and Catostylus mosaicus on Human Adenocarcinoma A549 Cells.

Nowadays, major attention is being paid to curing different types of cancers and is focused on natural resources, including oceans and marine environments. Jellyfish are marine animals with the ability to utilize their venom in order to both feed and defend. Prior studies have displayed the anticancer capabilities of various jellyfish. Hence, we examined the anticancer features of the venom of Cassiopea andromeda and Catostylus mosaicus in an in vitro situation against the human pulmonary adenocarcinoma (A549) cancer cell line. The MTT assay demonstrated that both mentioned venoms have anti-tumoral ability in a dose-dependent manner. Western blot analysis proved that both venoms can increase some pro-apoptotic factors and reduce some anti-apoptotic molecules that lead to the inducing of apoptosis in A549 cells. GC/MS analysis demonstrated some compounds with biological effects, including anti-inflammatory, antioxidant and anti-cancer activities. Molecular docking and molecular dynamic showed the best position of each biologically active component on the different death receptors, which are involved in the process of apoptosis in A549 cells. Ultimately, this study has proven that both venoms of C. andromeda and C. mosaicus have the capability to suppress A549 cells in an in vitro condition and they might be utilized in order to design and develop brand new anticancer agents in the near future.

Monometallic complexes of novel dihydrazone‐oxime ligand: Synthesis, structure, spectral, DFT, and in vitro bioactivity investigation against fungal, bacterial, and tumor cells

In the current study, uni‐metallic Cu2+, Ni2+, Mn2+, Co2+, and Zn2+ complexes of ONN‐tridentate dihydrazone‐oxime incorporating indolin‐2‐one moiety (HL,1) were synthesized and structurally characterized employing elemental, spectral, thermo‐gravimetric, magnetic, and molar conductivity measurements, to investigate the structure and composition of these new uni‐metallic complexes. According to the results of several analyses, the dihydrazone‐oxime behaved as a mono‐negative or neutral tridentate ONN chelator bound the metal cations in molar ratio (1M:1L) through the isatinic carbonylic oxygen, azomethine nitrogen, and nitrogen atom of deprotonated/protonated oximatic moiety forming uni‐metallic complexes with formulae [M(L)XYZ(H2O)].nH2O (where M = Cu2+ (2–4), Ni2+, Mn2+, Co2+, or Zn2+, X = Cl, CH3COO, or NO3, Y = H2O or 0, Z = H2O or 0, n = 2, 0) and [Cu (HL)(SO4)(H2O)]. The Cu2+ complexes were found to have a tetragonally distorted octahedral or square pyramidal geometry, whereas those of Mn2+, and Ni2+, exhibited a tetrahedral geometry but Co2+ complex demonstrated a distorted octahedral geometry. Based on DFT‐B3LYP technique and 6‐311G++(d,p) basis set, The DFT data confirmed the structural investigation of dihydrazone‐oxime and its complexes, revealing that the complexes reactivity is more than un‐complexed dihydrazone‐oxime. Moreover, quantum chemical parameters of dihydrazone‐oxime and its uni‐metallic complexes like the energies of both lowest unoccupied molecular orbital (ELUMO) and highest occupied molecular orbital (EHOMO), separation energy (ΔE = ELUMO − EHOMO), chemical potential, absolute electronegativity, absolute hardness, and absolute softness were obtained. According to the thermogravimetric analysis, the complexes breakdown in two to four disintegrating phases in range of temperature 25°C to 575°C leaving the oxide of metal or metal oxide contaminated with carbon. In vitro microbicide effect of the un‐complexed dihydrazone‐oxime and its uni‐metallic complexes toward various bacterial and fungal strains was tested by agar‐well diffusion method. It is demonstrated that the complexes are more effective than free dihydrazone‐oxime. The antitumor activity has been also analyzed against three cell lines including prostate adenocarcinoma (PC‐3), ovarian adenocarcinoma (SKOV3), and cervical cancer (HeLa) cell lines. Studies showed that all complexes have greater inhibition activity against the above three cell lines than the free dihydrazone oxime and the most effective compound was the Zn2+ complex (9) with IC50, 27.42, 35.16, and 46.77 μg/ml, respectively.

In Vitro Anticancer Activity of Novel Ciprofloxacin Mannich Base in Lung Adenocarcinoma and High-Grade Serous Ovarian Cancer Cell Lines via Attenuating MAPK Signaling Pathway.

Novel drugs are desperately needed in order to combat a significant challenge due to chemo-therapeutic resistance and bad prognosis. This research aimed to assess the anticancer activity of a newly synthesized ciprofloxacin Mannich base (CMB) on ovarian cancer (OVCAR-3) and lung cancer (A-549) cell lines and to investigate probable involved molecular mechanisms. The cytotoxic and pro-apoptotic impact of CMB on both cell lines was investigated using MTT assay, Annexin V assay, and cell cycle analysis, as well as caspase-3 activation. Western blotting was carried out to evaluate downstream targets of the MAPK pathway, while qRT PCR was used to evaluate the gene expression pattern of the p53/Bax/Bcl2 pathway. CMB treatment showed significantly reduced cell proliferation in both OVCAR-3 and A-549 cells with half maximum inhibitory concentration (IC50) = 11.60 and 16.22 µg/mL, respectively. CMB also induced apoptosis, S phase cell cycle arrest, and up-regulated expression of p53, p21, and Bax while down-regulated Bcl2 expression. CMB also halted cell proliferation by deactivating the MAPK pathway. In conclusion, CMB may be regarded as a potential antiproliferative agent for lung and ovarian cancers due to anti-proliferative and pro-apoptotic actions via inhibition of the MAPK pathway and p53/Bax/Bcl2.