Strong Anticancer Activity Research Articles

The polymeric fluoropyrimidine CF10 overcomes limitations of 5-FU in pancreatic ductal adenocarcinoma cells through increased replication stress

ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease soon to become the second leading cause of cancer deaths in the US. Beside surgery, current therapies have narrow clinical benefits with systemic toxicities. FOLFIRINOX is the current standard of care, one component of which is 5- Fluorouracil (5-FU), which causes serious gastrointestinal and hematopoietic toxicities and is vulnerable to resistance mechanisms. Recently, we have developed polymeric fluoropyrimidines (F10, CF10) which unlike 5-FU, are, in principle, completely converted to the thymidylate synthase inhibitory metabolite FdUMP, without generating appreciable levels of ribonucleotides that cause systemic toxicities while displaying much stronger anti-cancer activity. Here, we confirm the potency of CF10 and investigate enhancement of its efficacy through combination with inhibitors in vitro targeting replication stress, a hallmark of PDAC cells. CF10 is 308-times more potent as a single agent than 5-FU and was effective in the nM range in primary patient derived models. Further, we find that activity of CF10, but not 5-FU, is enhanced through combination with inhibitors of ATR and Wee1 that regulate the S and G2 DNA damage checkpoints and can be reversed by addition of dNTPs indicative of CF10 acting, at least in part, through inducing replication stress. Our results indicate CF10 has the potential to supersede the established benefit of 5-FU in PDAC treatment and indicate novel combination approaches that should be validated in vivo and may be beneficial in established regimens that include 5-FU.

In vitro pharmacological evaluation of Methanolic leaf extract of Calotropis procera for antifungal and anti-breast cancer activities.

Medicinal plants remained the primary choice worldwide from several centuries due to many therapeutic effects in the management of infectious and non-infectious diseases. Therefore, exploration of new medicinalplants as a green medicine has the major concern of many research groups. Microbial infections and different types of cancers in human are among the common health problems both in developing as well as in developed countries. Medicinal plants as a source of anti-microbial and anti-cancer agents are still in their initial stage in modern medicine. So current research work was planned to explore the anti-fungal and anticancer potential of Calotropis procera. C. procera leaves were collected from local area of Faisalabad, Pakistan, and phytochemical, anti-microbial, and anti-cancer activities were studied following reference methods. In vitro anti-microbial study of methanolic extracts of C. procera leaves against different strains of fungal was performed. Results showed that plant extract in a dose of 5 mg/mL have significant (P<0.05) antifungal activity. Moreover, the methanolic leaf extract of C. procera displayed strong anti-cancer activity in breast cancer cells (MCF-7), with a cytotoxic activityat 200μg/mL comparable to that found for Taxol as standard drug. Findings of current research work showed that the leaf extracts of C. procera has strong potential as an antibacterial, antifungal and anti-cancer agent. However, characterization and purification of phytochemicals is required to develop drug from natural resources.

Evidence to Support the Collaboration of SP1, MYC, and HIF1A and Their Association with microRNAs

This study provides evidence to support the concept proposed by Kimura et al. in 2023 that the inhibitors of SP1, MYC, and HIF1A should induce strong anticancer activity by reducing the expression of stem cell-related proteins. In LN229 and U87MG glioblastoma cells, either tetra-methyl-O-nordihydroguaiaretic acid (M4N) or tetra-acetyl-O-nordihydroguaiaretic acid (A4N) suppressed SP1 and only a few stem cell-related proteins and induced only a small amount of cell death; in contrast, the combination treatment of M4N with A4N greatly suppressed the expression of SP1, MYC, and HIF1A, as well as all of the stem cell-related proteins examined, and greatly induced cell death. The bioinformatic analysis showed that the proteins associated with SP1, MYC, and HIF1A were specifically involved in the regulation of transcription and that various microRNAs (miRNAs) that had been shown to induce either anti- or procancer activity were associated with SP1, MYC, and HIF1A, which suggested that the inhibition of SP1, MYC, and HIF1A could modulate the transcription of both coding and noncoding RNAs and affect cancers. These data overall supported our concept.

In vitro and In Silico Molecular Modeling Studies of Newly Synthesized Pyrrole Derivatives for their Antimicrobial and Anticancer Properties

Background: Pyrroles are biologically active scaffolds that can have a number of different effects. They also have unique pharmacophores inside their ring system that make it easier to make molecules that are more active. Significantly, in the past ten years, research has been conducted on the anti-bacterial properties, with a particular emphasis on drug-resistant Gram-positive and Gram-negative pathogens such as mycobacteria. Additionally, scaffolds based on pyrroles were utilized in the production of anti-tumor medicines that function by modulating or suppressing genes. Objective: This research aimed to create new pyrrole derivatives by chemical means and evaluate their antimicrobial and anticancer properties. Methods: By reacting diverse 1H-pyrrole-2-carbohydrazide derivatives with benzaldehyde under normal conditions, a number of pyrrole variations were created. IR, mass spectroscopy, NMR, and elemental analysis were used to characterize the synthesized compounds. The serial dilution method was used to assess antimicrobial activity, along with a molecular docking study against the enzyme α-topoisomerase II (α-Topo II), which effectively controls the topology of DNA. This enzyme is strongly expressed in rapidly dividing cells and is crucial for transcription, replication, and chromosome structure. Pyrrole and its synthetic derivatives are known to exhibit strong anticancer activity by specifically targeting α-Topo II, which has led multiple researchers to investigate α-Topo II inhibitors as potential anticancer medicines. Consequently, designing pyrroline derivatives is interesting since the succinimide portion of the joined heteroaromatic molecule can selectively engage with the ATP binding pocket via the hydrogen bond network. Newer synthesized compounds were also docked via Schrodinger 2022-4 into the active pocket of the three-dimensional crystallographic structure of the ATP site of human topoisomerase IIα (htopo IIα) (PDB ID: 1zxm). Results: Among the newly synthesized pyrrole derivatives, compounds demonstrated significant anti- microbial activity. In addition, the AutoDock Vina application was used to perform in-silico docking computations. Compounds 1a and 1h were found to have a stronger antiproliferative effect than compounds against MCF-07 breast cancer cell linen our study, ligands 1a and 1b exhibited better binding energies of -5.049 and -5.035 kcal/mol, respectively. Most of the synthesized pyrrole derivatives showed promising antiproliferative effects; however, further in vivo investigations are needed to confirm or refute these results. Conclusion: The results of this investigation show that pyrrole derivatives have the potential to be effective antimicrobial and anticancer agents. While resolving safety issues, the structural alterations carried out in this study enhanced the compounds' medicinal capabilities. To clarify the underlying mechanisms of action and enhance the pharmacological characteristics of these new pyrrole derivatives, further research is necessary.

Growth hormone-releasing hormone and cancer.

The hypothalamic hormone growth hormone-releasing hormone (GHRH), in addition to promoting the synthesis and release of growth hormone (GH), stimulates the proliferation of human normal and malignant cells by binding to GHRH-receptor (GHRH-R) and its main splice variant, SV1. Both GHRH and GHRH-Rs are expressed in various cancers, forming a stimulatory pathway for cancer cell growth; additionally, SV1 possesses ligand independent proliferative effects. Therefore, targeting GHRH-Rs pharmacologically has been proposed for the treatment of cancer. Various classes of synthetic GHRH antagonists have been developed, endowed with strong anticancer activity in vitro and in vivo, in addition to displaying anti-inflammatory, antioxidant and immune-modulatory functions. GHRH antagonists exert indirect effects by blocking the pituitary GH/hepatic insulin-like growth factor I (IGF-I) axis, or directly inhibiting the binding of GHRH on tumor GHRH-Rs. Additionally, GHRH antagonists block the mitogenic functions of SV1 in tumor cells. This review illustrates the main findings on the antitumor effects of GHRH antagonists in experimental human cancers, along with their underlying mechanisms. The development of GHRH antagonists, with reduced toxicity and high stability, could lead to novel therapeutic agents for the treatment of cancer and inflammatory diseases.

Auranofin loaded silk fibroin nanoparticles for colorectal cancer treatment.

Colorectal cancer (CRC) is the second most common cause of cancer related deaths worldwide and the prevalence in young people especially is increasing annually. In the search for innovative approaches to treat the disease, drug delivery systems (DDS) are promising owing to their unique properties, which allow improved therapeutic results with lower drug concentrations, overcoming drug resistance and at the same time potentially reducing side effects. Silk fibroin is a biopolymer that can be processed to obtain biocompatible and biodegradable nanoparticles that can be efficiently loaded by surface adsorption with small-molecule therapeutics and allow their transport and sustained release by modulating their pharmacokinetics. Auranofin (AF) has recently been repurposed for its strong anticancer activity and is currently in clinical trials. Its mechanism of action is through the inhibition of thioredoxin reductase enzymes, which play an essential role in several intracellular processes and are overexpressed in some tumours. Taking into account that AF has a low solubility in water, we propose silk fibroin nanoparticles (SFN) as AF carrier in order to improve its bioavailability, increasing cellular absorption and preventing its degradation or avoiding some resistance mechanisms. Here we report the preparation and characterization of a new formulation of AF-loaded silk fibroin nanoparticles (SFN-AF), its functionalization with FITC for the analysis of cellular uptake, as well as its cytotoxic activity against cell lines of human colorectal cancer (HT29 and HCT116) in both 2D and 3D cell cultures. 3D spheroid models provide a 3D environment which mimics the 3D aspects of CRC observed in vivo and represents an effective 3D environment to screen therapeutics for the treatment of CRC. The loaded nanoparticles showed a spherical morphology with a hydrodynamic diameter of ~ 160nm and good stability in aqueous solution due to their negative surface charges. FESEM-EDX analysis revealed a homogeneous distribution of Au clusters with high electron density on the surface of the nanoparticles. SFN-AF incubated in phosphate buffer at 37°C released 77% of the loaded AF over 10 days, showing an initial burst and then sustained release. Flow cytometry analysis showed that FITC-SFN-AF was efficiently internalized by both cell lines, which was confirmed by confocal microscopy imaging. SFN enhanced the cytotoxicity of AF in 2D cultures in both CRC lines. Promising results were also obtained in 3D culture paving the way for future application of this strategy as a therapy for CRC.

Antiproliferative Effects of Methanolic Fruit Extract of Solanum xenthocarpum (L.) on Human Breast Cancer Cells.

Solanum xanthocarpum, a perennial herb native to India, contains steroidal glycoalkaloids with notable anticancer properties. This study investigated the antioxidant and antiproliferative effects ofmethanolic fruit extract of S. xanthocarpum on human breast cancer cells (MDA-MB-231). Phytochemical screening and LC-HRMS analysis confirmedpresence of various primary and secondary metabolites. Antioxidant activity was assessed through DPPH, ABTS radical scavenging, reducing power, and phosphomolybdate assays. The extract demonstrated significant antioxidant potential with EC50 values of 60.10 ± 0.88 µg/mL (DPPH) and 392.29 ± 3.93 µg/mL (ABTS). Cytotoxicity against MDA-MB-231 cells was evaluated via morphological analysis, MTT assays, and IC50 determination (24.19 ± 0.56 µg/L). Apoptosis was confirmed using dual staining techniques (AO/EB, Hoechst 33342/PI, DAPI), revealing condensed nuclei, apoptotic bodies, and reduced mitochondrial membrane potential, as indicated by Rhodamine staining. Additionally, increased reactive oxygen species (ROS) levels were observed using H2-DCF-DA staining. The total phenolic and flavonoid contents of the extract were 127.78 ± 3.547 mg GAE/g and 98.06 ± 4.289 mg QE/g, respectively. These findings suggest that the methanolic fruit extract of S. xanthocarpum possesses strong antioxidant and anticancer activities, indicating its potential role in cancer treatment. Further studies are warranted to explore its bioactive compounds for developing novel anticancer therapies.

3D-printed implants loaded with acriflavine for glioblastoma treatment

Drug delivery routes play an essential role in determining the efficacy and safety of medications. This study focused on the development and optimization of 3D-printed reservoir type implants as a combinational therapy drug delivery system for Glioblastoma Multiforme (GBM) post-surgery, possessing also antibacterial properties. In this study, we used a multimodal agent, Acriflavine (ACF) as an alternative drug to treat GBM. To date, ACF is used only as an antiseptic agent, although it has been shown to possess strong anticancer activities. ACF and a low molecular weight PCL were loaded into 3D-printed reservoir-type implants for sustained drug delivery. The study demonstrated that ACF implants exhibited sustained drug release kinetics, with faster release during the initial 30 days, followed by a gradual decrease over 90 days. This controlled release profile enhances the effectiveness of ACF delivery to tumour targets while minimizing side effects associated with systemic administration. In vitro experiments confirmed the inhibitory activity of ACF against GBM cells compared to non-tumour cells. The study also highlighted the bacteriostatic effects of ACF, making the implants potentially useful for post-surgery infection management, particularly against S. aureus, a common bacterial infection associated with brain surgery. The long-term drug-release capabilities of the implants make them attractive candidates for both tumour inhibition and antibacterial treatment. The study suggests that the developed ACF delivery systems have the potential for future clinical studies. Their ability to provide increased drug efficacy without systemic toxicity makes them promising candidates for cancer therapy and post-surgery infection management.

Enhanced Production and Therapeutic Evaluation of TP4 Peptide in Pichia pastoris Against Hepatocellular Carcinoma HUH-7 Cells

Tilapia piscidin 4 (TP4), a cationic antimicrobial peptide, is recognized for its diverse biological roles, including antibacterial, wound-healing, and anticancer properties. Herein, the codon-optimized sequence of TP4 peptide was expressed using the pPICZαA expression vector containing the AOX1 promoter, a strong and inducible promoter, in the Pichia pastoris KM71H expression system. Recombinant TP4 peptide was purified by Ni-NTA affinity chromatography. After purification, the anticancer activity of TP4 was assessed in HUH-7 hepatocellular carcinoma cells, and the underlying mechanisms were determined. In the present study, it was demonstrated for the first time that recombinant TP4 displayed strong anticancer activity in the human HUH-7 cell line. The TP4 antimicrobial peptide can be used as a competitive candidate for the treatment of cancer cells due to its anticancer effects.

SZ-685C inhibits the growth of non-functioning pituitary adenoma by down-regulating miR-340-3p and inducing autophagy

BackgroundSZ-685C, an anthracycline compound derived from the mangrove endophytic fungus Halorosellinia sp. (No. 1403) collected from the South China Sea, has shown strong anticancer activities. Non-functioning pituitary adenomas (NFPAs) are a type of tumor that can be challenging to manage clinically and have a significant unmet medical need. Our research has found that SZ-685C showed an inhibitory effect on the viability, migration ability, and proliferation ability of a human non-functioning pituitary tumor-derived folliculostellate (PDFS) cell line. MethodsSZ-685C was prepared and purified from the mangrove endophytic fungus No. 1403. PDFS cells were exposed to SZ-685C, and the effect of SZ-685C on PDFS cells was evaluated. RNA sequencing was used to analyze the miRNA expression profile in PDFS cells of the control group and SZ-685C-treated group. Quantitative polymerase chain reaction (qPCR) was performed to verify the expression of selected miR-340-3p. The effects of SZ-685C on PDFS cells after overexpression of miR-340-3p were evaluated. Dual-luciferase reporter assays showed PPP1CB is a direct target of miR-340-3p. Finally, the action pathway of the selected miR-340-3p was predicted and evaluated through bioinformatics analysis. ResultsSZ-685C reduced cell viability in PDFS cells, accompanied by inhibition of migration ability and proliferation ability. The IC50 value for 24 h is 9.144 ± 0.991 μM, and for 48 h is 4.635 ± 0.551 μM. SZ-685C increased the protein levels of Beclin 1, the ratio of LC3-II to LC3-I, and LAMP-1, and down-regulated p62. MiRNA sequencing and further validation showed that miR-340-3p significantly decreased in PDFS cells treated with SZ-685C. After overexpression of miR-340-3p, the inhibition of viability, migration ability, proliferation ability, and autophagy-promoting effect of SZ-685C on PDFS cells were weakened. SZ-685C caused a decrease in PPP1CB expression and activation of the ERK pathway in PDFS cells, and this trend was reversed after overexpression of miR-340-3p. ConclusionsSZ-685C downregulates the expression of miR-340-3p in PDFS cells, thereby reducing the expression of PPP1CB and activating the ERK pathway to promote autophagic cell death, leading to inhibition of PDFS cell growth.

Dual Antimicrobial and Anticancer Activity of Membrane-Active Peptide BP52.

The linear undecapeptide BP52 was previously reported to have antibacterial activity against phytopathogenic bacteria species. Due to the structural similarities to naturally occurring cationic helical antimicrobial peptides, it was speculated that this peptide could potentially target microbial pathogens and cancer cells found in mammals. Consequently, this study aims to further investigate the structural and biological properties of this peptide. Our findings indicate that BP52 exhibits strong antimicrobial and anticancer activity while displaying relatively low levels of hemolytic activity. Hence, this study suggests that BP52 could be a potential lead compound for drug discovery against infectious diseases and cancer. Besides, new insights into the relationships between the structure and the multifunctional properties of antimicrobial peptides were also explored.

Discovery of novel 2-substituted 2, 3-dihydroquinazolin-4(1H)-one derivatives as tubulin polymerization inhibitors for anticancer therapy: The in vitro and in vivo biological evaluation

A series of novel 2-substituted 2, 3-dihydroquinazolin-4(1H)-one derivatives were designed, synthesized and estimated for their in vitro antiproliferative activities against HepG2, U251, PANC-1, A549 and A375 cell lines. Among them, compound 32 was the most promising candidate, and displayed strong broad-spectrum anticancer activity. The mechanism studies revealed that compound 32 inhibited tubulin polymerization in vitro, disrupted cell microtubule networks, arrested the cell cycle at G2/M phase, and induced apoptosis by up-regulating the expression of cleaved PARP-1 and caspase-3. Furthermore, molecular docking analysis suggested that compound 32 well occupied the binding site of tubulin. In addition, compound 32 exhibited no significant activity against 30 different kinases respectively, indicating considerable selectivity. Moreover, compound 32 significantly inhibited the tumour growth of the HepG2 xenograft in a nude mouse model by oral gavage without apparent toxicity. These results demonstrated that some 2-substituted 2, 3- dihydroquinazolin-4(1H)-one derivatives bearing phenyl, biphenyl, naphthyl or indolyl side chain at C2-position might be potentially novel antitumor agents as tubulin polymerization inhibitors.

In Vitro Anticancer Potential of Cardamom (Elettaria cardamomum) Essential Oil Against TNBC, Glioma and Kidney Cancer

Background: Green cardamom (Elettaria cardamomum (L.) Maton), a member of the Zingiberaceae family, is widely recognized for its use as a spice and traditional medicine. It is commonly used for treating gastric, cardiac, and kidney disorders, as well as infections and inflammatory conditions. Cardamom essential oil, known for its high content of bioactive compounds such as 1,8-cineole and α-terpinyl acetate, has been studied for its diverse biological activities, including antioxidant, antibacterial, anti-inflammatory, and anticancer effects. However, little is known about its anticancer potential against MDA-MB-231 (triple-negative breast cancer), U87 (glioblastoma), and HEK 293 (kidney) cell lines, especially in the context of cardamom oil sourced from Iraq. Methods: Cardamom essential oil was extracted via hydro-distillation from cardamom fruits collected in Erbil, Iraq, and its chemical composition was analyzed using gas chromatography-mass spectrometry (GC-MS). The oil’s anticancer activity was evaluated using the MTT assay against MDA-MB-231, U87, and HEK 293 cell lines. The cells were treated with various concentrations of cardamom essential oil, and cell viability was measured after 24 hours. The IC50 values were calculated to determine the oil’s efficacy. Results: GC-MS analysis revealed 33 compounds in the essential oil, with 1,8-cineole (42.37%) and α-terpinyl acetate (22.14%) being the predominant constituents. The MTT assay demonstrated that cardamom essential oil significantly reduced cell viability in MDA-MB-231 and HEK 293 cell lines in a dose-dependent manner, with IC50 values of 96.95 µl/ml and 157.44 µl/ml, respectively. However, the oil was less effective against U87 cells, showing only 40.67% inhibition at the highest concentration (500 µl/ml). Conclusion: Cardamom essential oil, rich in 1,8-cineole and α-terpinyl acetate, exhibited strong anticancer activity against MDA-MB-231 and HEK 293 cell lines, highlighting its potential as a therapeutic agent for triple-negative breast cancer. Further studies are needed to explore its full potential and mechanisms of action against different cancer types.

Bioactivity of selenium nanoparticles biosynthesized by crude phycocyanin extract of Leptolyngbya sp. SSI24 cultivated on recycled filter cake wastes from sugar-industry

BackgroundBeet filter cake (BFC) is a food-grade solid waste produced by the sugar industry, constituting a permanent source of pollution. Cyanobacteria are considered a sustainable resource for various bioactive compounds such as phycocyanin pigment with valuable applications. This study aimed to use beet filter cake extract (BFCE) as an alternative medium for the economic cultivation of cyanobacterium Leptolyngbya sp. SSI24 PP723083, then biorefined the bioactive component such as phycocyanin pigment that could be used in the production of selenium nanoparticles.ResultsThe results of the batch experiment displayed that the highest protein content was in BG11medium (47.9%); however, the maximum carbohydrate and lipid content were in 25% BFCE (15.25 and 10.23%, respectively). In addition, 75% BFCE medium stimulated the phycocyanin content (25.29 mg/g) with an insignificant variation compared to BG11 (22.8 mg/g). Moreover, crude phycocyanin extract from Leptolyngbya sp SSI24 cultivated on BG11 and 75% BFCE successfully produced spherical-shaped selenium nanoparticles (Se-NPs) with mean sizes of 95 and 96 nm in both extracts, respectively. Moreover, XRD results demonstrated that the biosynthesized Se-NPs have a crystalline nature. In addition, the Zeta potential of the biosynthesized Se-NPs equals − 17 mV and − 15.03 mV in the control and 75% BFCE treatment, respectively, indicating their stability. The biosynthesized Se-NPs exhibited higher effectiveness against Gram-positive bacteria than Gram-negative bacteria. Moreover, the biosynthesized Se-NPs from BG11 had higher antioxidant activity with IC50 of 60 ± 0.7 compared to 75% BFCE medium. Further, Se-NPs biosynthesized from phycocyanin extracted from Leptolyngbya sp cultivated on 75% BFCE exhibited strong anticancer activity with IC50 of 17.31 ± 0.63 µg/ml against the human breast cancer cell line.ConclusionsThe BFCE-supplemented medium can be used for the cultivation of cyanobacterial strain for the phycocyanin accumulation that is used for the green synthesis of selenium nanoparticles that have biological applications.Graphical

Inhibition of human DNA alkylation damage repair enzyme ALKBH2 by HIV protease inhibitor ritonavir

The human DNA repair enzyme AlkB homologue-2 (ALKBH2) repairs methyl adducts from genomic DNA and is overexpressed in several cancers. However, there are no known inhibitors available for this crucial DNA repair enzyme. The aim of this study was to examine whether the first-generation HIV protease inhibitors having strong anti-cancer activity can be repurposed as inhibitors of ALKBH2. We selected four such inhibitors and performed in vitro binding analysis against ALKBH2 based on alterations of its intrinsic tryptophan fluorescence and differential scanning fluorimetry. The effect of these HIV protease inhibitors on the DNA repair activity of ALKBH2 was also evaluated. Interestingly, we observed that one of the inhibitors, ritonavir, could inhibit ALKBH2-mediated DNA repair significantly via competitive inhibition and sensitized cancer cells to alkylating agent methylmethane sulfonate (MMS). This work may provide new insights into the possibilities of utilizing HIV protease inhibitor ritonavir as a DNA repair antagonist.

CD47-SIRPα Blockade Sensitizes Head and Neck Squamous Cell Carcinoma to Cetuximab by Enhancing Macrophage Adhesion to Cancer Cells.

Developing effective treatments for patients with head and neck squamous cell carcinoma (HNSCC) is a significant challenge. Cetuximab, a first-line targeted therapy for HNSCC, exhibits limited efficacy. Here, we used pooled CRISPR screening to find targets that can synergize with cetuximab and identified CD47 as the leading candidate. Rather than inhibiting cancer cell proliferation, CD47 inhibition promoted cetuximab-triggered antibody-dependent cellular phagocytosis (ADCP), thereby enhancing macrophage-mediated cancer cell removal. The combination of CD47-signal-regulatory protein α (SIRPα) blockade and cetuximab demonstrated strong anticancer activity in vivo. In addition to blocking the phagocytosis checkpoint, CD47-SIRPα inhibition upregulated CD11b/CD18 on the surface of macrophages, which accelerated intercellular adhesion between macrophages and cancer cells to enhance subsequent phagocytosis. Inhibition of the interaction between macrophage CD11b/CD18 and cancer cell intercellular adhesion molecule-1 (ICAM1) eliminated the intercellular adhesion and phagocytosis induced by CD47-SIRPα blockade. Thus, CD47-SIRPα blockade enhances ADCP through CD11b/CD18-ICAM1-mediated intercellular adhesion and sensitizes HNSCC to cetuximab. Significance: CD47-SIRPα blockade increases surface CD11b/CD18 on macrophages to enhance adhesion to cancer cells, resulting in robust synergistic phagocytosis in combination with cetuximab treatment in head and neck squamous cell carcinoma.

The effectiveness of semi-wild Sumatran mango (Mangifera spp.) leaves as a phytotherapy agent for breast cancer

Background Breast cancer ranks first in the world, standing at a mortality rate of 24.5% per year and is the leading cause of cancer death in Indonesia. The current management of breast cancer therapy is considered less effective because of its careful use due to side effects that are detrimental to the patient. The semi-wild species from Sumatra are neglected and underutilized species but have the potential as a therapeutic agent. Previous research has revealed that this species of mango is high in antioxidant compounds. Objective This study was carried out to discover the anticancer activities of the semi-wild mango species via inhibitory activities and morphological changes in Michigan Cancer Foundation-7 (MCF-7) cells. Materials and methods The IC50 value of Mangifera sumatrana, Mangifera foetida, and Mangifera laurina leaves in n-hexane, ethyl-acetate, and methanol extracts was determined using the reagent 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Data were analyzed by two-way analysis of variance using IBM SPSS Statistics 21. Results and conclusion M. laurina n-hexane extracts exhibited anticancer activity (IC50 13.25 ppm). Nonpolar solutions were chosen as the most effective extraction solvent in anticancer tests because lipids in nonpolar solvents can hit the lipid bilayer. A hexane fraction was created by separating the majority of nonpolar fatty acid esters, and this fraction had a considerable impact on cytotoxic and apoptotic effects on MCF-7 cells. Therefore, all treatments can transform MCF-7 cells’ morphology into blackened dead cells that are degraded into small parts, such as apoptotic bodies in cells undergoing apoptotic processes. MTT assays against MCF-7 on three species of semi-wild Sumatran mango in different extraction solvents showed that n-hexane extracts of M. laurina had stronger anticancer activity than other samples. This study provides new information to support the development of standardized herbal medicines and phytopharmaca in the future.

In-vitro Evaluation for Anticancer Activity of Extract of Asparagus racemosus

The main purpose of this study is to look into how protective Asparagus racemosus leaves are in-vitro. Cancer is a major reason people die around the world. Many of the bad effects of the allopathic drugs that are now used to treat cancer have caused people to turn to plant medicine. Some of the solvents that were used in the sequential solvent extraction method were chloroform, ethanol and ethyl acetate. The chloroform extract had a higher percentage yield compared to the other extracts. Because it had anticancer activity in-vitro, the therapeutically active extract was picked to have anticancer activity in living things. The MTT test was used to see if the chloroform, ethyl acetate, and ethanol extracts could help fight cancer in HeLa cell types. The MTT assay showed that chloroform and ethyl acetate extracts had strong anticancer activity. These two extracts were chosen for study into how they work against cancer in living things

Dinuclear Tridentate Ru(II) Complex with Strong Near-Infrared Light-Triggered Anticancer Activity.

The design of the dinuclear Ru(II) complex (Ru2) with strong near-infrared (NIR) absorption properties has been reported for efficient anticancer phototherapy. Under 700 nm LED light excitation, Ru2 exhibited remarkable synergistic type I/II photosensitization ability and photocatalytic activity toward intracellular biomolecules. Ru2 showed impressive 700 nm light-triggered anticancer activity under normoxia and hypoxia compared with the clinically used photosensitizer Chlorin e6. The mechanistic studies showed that Ru2 induced intracellular redox imbalance and perturbed the energy metabolism and biosynthesis in A549 cancer cells. Overall, this work provides a new strategy for developing efficient metal-based complexes for anticancer phototherapy under NIR light.

Synergistic inhibition of CXCL8 following MRTX1133 treatment with ONC212 or 5-FU in KRAS G12D and G12V mutant CRC and PDAC cell lines.

e15196 Background: CXCL8, serves as a crucial multifunctional cytokine that plays a significant role in regulating tumor growth, invasion, and migration. Although in some cancers the critical role of CXCL8 in patient prognosis and disease progression is stablished but its role in CRC &amp; PDAC patients is under investigation. High levels of CXCL8 in tumor microenvironment (TME) and association with cancer stem cell survival, immune surveillance escape &amp; metastasis make it an interesting therapeutic target. Both CRC &amp; PDAC are among the deadliest cancers with dismal prognosis. The need for novel therapeutics with a focus on TME is emerging. MRTX1133 was identified as an inhibitor of KRASG12D. ONC212 is a fluorinated imipridone with strong anti-cancer activity in nM range and preclinical efficacy against pancreatic and other malignancies. Here we report the synergistic inhibition of CXCL8 in both KRAS G12D &amp; KRAS G12V cell lines with use of KRAS G12D inhibitor in combination with 5-FU or ONC212. Methods: Different CRC &amp; PDAC cells were treated with MRTX1133 with 5-FU or ONC212 cytokine profiling at 48h time point was done. Human protein atlas was used for protein and RNA data &amp;TCGA data for survival was used. Results: We previously have shown the synergistic inhibition of pERK and cytokine alteration between MRTX1133 KRAS G12D inhibitor with 5FU or ONC212 in both cell lines with KRAS G12D &amp; KRAS G12V mutation (Tajiknia V et al. AACR 2023 annual meeting). In LS513 KRAS G12D CRC cell line, treatment of ONC212, MRTX1133 and combination of both showed a decrease of 52.36%,58.83% and 71.65% respectively in CXCL8 levels compared to control at 48h time point. In HPAF-II KRAS G12V PDAC cell line, treatment of ONC212, MRTX1133 and combination of both resulted in 38.69%, 64.44%, 57% inhibition of CXCL8 levels respectively compared to control. In SW480 KRAS G12V CRC cell line, treatment of ONC212, MRTX1133 and combination of both demonstrated 25.7%,47.3% and 66.5% inhibition in CXCL8 level respectively compared to control at 48h time point. Single treatment of MRTX1133 caused a decline in CXCL8/IL-8 levels by 30% while single treatment of 5-FU showed a 36% decrease, the combination of both resulted in more than 55% decrease compared to control in LS513 KRAS G12D cell line. In SW480 KRAS G12V cell line, combination of 5-FU &amp; MRTX1133 showed 30% inhibition while in Capan-2 PDAC KRAS G12V cells the same combination showed a 48.2% reduction in CXCL8 compared to control at 48h time point. TCGA data for RNA shows low specificity of CXCL8 for cancer type but it is significantly high in CRC and PDAC. Protein concentration in the Pan-cancer cohort shows significant high level of CXCL8 in CRC. Conclusions: Considering the important role of KRAS mutations and CXCL8 in pathogenesis of CRC &amp; PDAC, the effective inhibition of CXCL8 with the use of targeted therapy in combination could enhance treatment response and patient survival.