Anticancer Activity Research Articles

A Mini-Review on the Structural Characteristics and Anticancer Activity of Nagilactones

Abstract: Natural products provide abundant resources for the development of new drugs. Podocarpus nagi is an arbor of Podocarpus L'Hér. ex Persoon. Its fruits, leaves, and roots exhibit a broad spectrum of pharmacological activities (such as antitumor, plant growth regulation, termite killing, and insect larval toxicity), which have been used in Yao folk for a long history. Nagilactone is one of the key components discovered in Podocarpus nagi, which has a variety of structures and a broad spectrum of antitumor activities. In this mini-review, the structures and spectral characteristics, together with the antitumor activities and the structure-activity relationships of nagilactones, are summarized by searching the database in order to provide detailed references for researchers to elucidate and modify their structures.

Evaluation of attenuated Salmonella Typhimurium (STMΔznuABC) anticancer activity on canine mammary cancer-associated fibroblasts

Bacteria-mediated treatments gained increasing attention as alternative therapies against tumors. An attenuated mutant strain of Salmonella enterica serovar Typhimurium (STMΔznuABC) has recently been considered as a potential new anti-cancer strategy. However, it is unclear whether this activity is tumor-induced or species-specific, and no data are available regarding STMΔznuABC on canine mammary tumors (CMTs). This study aimed to investigate the ability of STMΔznuABC in modulating the response of CMTs, focusing on cancer-associated fibroblasts. Four CMT cell lines (CF33, TM51, TM52 TM53) were treated with STMΔznuABC. Then, antiproliferative activity (MTT assay), bacterial invasion, and CMT cell lines gene expression analysis (RT-qPCR) of genes involved in immune response and cancer aggressiveness were evaluated. STMΔznuABC penetrated in TM51, TM52, TM53, and CF33 cell lines, causing a significant reduction of cell viability. Moreover, the expression of several genes was significantly modulated in all CMT cell lines: STMΔznuABC infection determined a significant up-regulation of CXCL8, IL18, IL10, TLR4 and RAD51, while CD14, IL6, CXCR4, P53, PTEN, STAT5, TLR5 and TGFB were downregulated in TM53. In CF33, CXCL8 and P53 were upregulated, while MYD88, MD2, IL18, TLR4,5, TGFB were downregulated. In TM52, CXCL8, CD44 and MD2 were upregulated and PTEN was downregulated, while in TM51 CXCL8, CD44 and ErbB2 were downregulated. We demonstrated the anti-proliferative and immuno-modulatory activity of STMΔznuABC in CMTs, paving the way for potential new anti-cancer treatments.

Chlorine containing tetrahydropyrimidines: Synthesis, characterization, anticancer activity and mechanism of action

The aim of the presented research was to explore anticancer potential of eleven newly synthesized tetrahydropyrimidine derivatives. The compounds were synthesized via Biginelli multicomponent one-pot reaction using different derivatives of vanillin, ethyl 4-chloroacetoacetate and (N-methyl)urea. The cytotoxic effects of the compounds were examined on three human malignant cell lines (HeLa, K562, and MCF7), and normal lung fibroblasts MRC-5. The mechanisms of anticancer activity were examined for two compounds 4a and 4b which showed the strongest and selective cytotoxicity against chronic myelogenous leukaemia K562 cells (IC50 = 1.76 ± 0.09, and.1.66 ± 0.05, respectively). The changes of matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and vascular endothelial growth factor A (VEGFA) were investigated in the K562 cell line, as well as oncomiRNA miR-10b, miR-23a described to have both features, depending on a specific type of malignancy, and miR-34a with mostly described as a tumour suppressor.

Rational design, synthesis, and anticancer evaluation of pyridine and substituted aryl linked 1,3,4-oxadiazole derivatives

A new series of Pyridine and substituted aryl linked 1,3,4-oxadiazole derivatives (7a-j) were designed, synthesized and evaluated for their anticancer activities against HeLa, MDA-MB-231, MCF-7, and A549 cell lines by using standard MTT reduction assay protocol with doxorubicin as standard drug. It is very important to mention that all these synthesized derivatives do not show any cytotoxicity on HEK-293 kidney cell lines. Among them, the compound 7d showed better activity against HeLa and MCF-7 cell lines with IC50 values of 1.8 ± 0.3 µM and 1.3 ± 0.11 µM.

Preliminary anticancer activity of Carpobrotus edulis (L.) Bolus exposed to low and high temperature conditions against cervical cancer

Introduction: Environmental temperature conditions might influence the composition of secondary metabolites in certain medicinal plants. This study aimed to examine how some of the phytochemicals and anticancer properties of Carpobrotus edulis may be impacted by temperature conditions. Methods: The plant specimens were kept in growth chambers at 15/10 °C and 45/35 °C (day/night), and harvested at 48-hour intervals (48, 96, and 144 hours). Control conditions were maintained at 25/15 °C. Standard phytochemical colour tests were used to determine the presence of eight phytochemicals. The anticancer activity against cervical cancer cell lines was determined using cell viability assay, cell morphology, Hoechst staining, and wound healing assays. Results: The phytochemical screening showed the presence of all tested phytochemicals (phenolics, flavonoids, terpenoids, saponins, tannins, steroids, and cardiac glycosides) in all treatments except for saponins in the 96- and 144-hour temperature treatments. A noteworthy IC50 value of 284.9 µg/mL was determined from the methanolic leaf extract exposed to high temperatures for 144 hours against cervical cancer. Treatment with this extract suggested changes in cancer cell morphology, signs of apoptosis, and cell migration inhibition. Conclusion: The preliminary results obtained suggest that the C. edulis methanolic extract has potential anticancer properties against cervical cancer. These observations may have implications for the indigenous plant use in treating various ailments and broaden the type of anticancer research involving this plant.

Molecular Actions of Enicostemma hyssopifolium Whole Plant Extract on HPV18-Infected Human Cervical Cancer (HeLa) Cells.

Enicostemma hyssopifolium (E. hyssopifolium) contains several bioactive compounds with anti-cancer activities. This study was performed to investigate the molecular effects of E. hyssopifolium on HPV18-containing HeLa cells. The methanol extract of E. hyssopifolium whole plant was tested for cytotoxicity by MTT assay. A lower and higher dose (80 and 160 μg/mL) to IC50 were analyzed for colonization inhibition (Clonogenic assay), cell cycle arrest (FACS analysis), and induction of apoptosis (AO/EtBr staining fluorescent microscopy and FACS analysis) and DNA fragmentation (comet assay). The HPV 18 E6 gene expression in treated cells was analyzed using RT-PCR and qPCR. A significant dose-dependent anti-proliferative activity (IC50 - 108.25±2 μg/mL) and inhibition of colony formation cell line were observed using both treatments. Treatment with 80 μg/mL of extract was found to result in a higher percent of cell cycle arrest at G0/G1 and G2M phases with more early apoptosis, while 160 μg/mL resulted in more cell cycle arrest at SUBG0 and S phases with late apoptosis for control. The comet assay also demonstrated a highly significant increase in DNA fragmentation after treatment with 160 μg/mL of extract (tail moments-19.536 ± 17.8), while 80 μg/mL of extract treatment showed non-significant tail moment (8.152 ± 13.0) compared to control (8.038 ± 12.0). The RT-PCR and qPCR results showed a significant reduction in the expression of the HPV18 E6 gene in HeLa cells treated with 160 μg/mL of extract, while 80 μg/mL did not show a significant reduction. The 160 μg/mL methanol extract of E. hyssopifolium demonstrated highly significant anti-cancer molecular effects in HeLa cells.

A comparative analysis on impact of drying methods on metabolite composition in broccoli microgreens

This study evaluated the effect of three preparation methods—fresh, microwave drying, and air fryer drying—on the bioactive compounds in broccoli microgreens. Microgreens, harvested 12 days after sowing, were processed and analyzed using LC-MS/MS. The data analysis involved ANOVA, Tukey's HSD, heatmaps, PCA, hierarchical clustering, and KEGG pathway analysis. While ANOVA showed no significant differences (P > 0.05) in the total quantity of compounds between the methods, the presence or absence of specific compounds varied significantly (P < 0.05) between the Fresh, Microwaved, and Air Fried Samples. Heatmap analysis indicated a moderate positive correlation between the Fresh Sample and both processed samples. PCA and KMeans clustering revealed distinct differences in compound concentrations across the methods, with box plots highlighting variability within clusters. The dominant compounds varied, with the Fresh Sample exhibiting the highest mean antioxidant and anticancer activity. All methods primarily affected metabolic and secondary biosynthesis pathways. This study underscores the importance of preparation methods in influencing the nutritional and bioactive compound composition of broccoli microgreens, with implications for food science and metabolic research. Optimizing these techniques could further enhance their health benefits.

Chemical profiling of fungal metabolites via the OSMAC approach: Novel identification of Brianthein W from an endophytic fungus, Hypomontagnella monticulosa Zg15SU

In the previous report, we reported that Hypomontagnella monticulosa originating from the rhizome of Zingiber griffithii was known to produce a marine-derived natural product. An OSMAC-based approach was designed by modifying the nutritional composition of the growth medium to investigate any possible new metabolites produced by the strain. The culture filtrate and biomass were conditioned through the use of three basal media, namely, Czapek-dox, potato dextrose, and Wickersham broth medium. GC-MS and multivariate analysis was performed to distinguish the chemicals and determine their composition in the tested extracts. Antimicrobial activity was tested against selected human pathogenic microbes using the disk-diffusion method. The MeOH extract of both culture filtrate and biomass from different fermentation media revealed that the majority of identified compounds (n=40) were found in Wickerham medium (n=23), which is later termed as MeOH-Wi. The chemical composition of MeOH-Wi was fatty acids (21.74%), followed by terpenoids (17.38%), cyclosiloxane (13.04%), aldehydes (13.04%), alkenes (8.7%), hydrocarbons (8.7%), esters (8.7%), alkaloids (4.35%), and an unclassified compound, the 9,9-Dimethyl-3,7-diazabicyclo[3.3.1]nonane. The numerous chemical compounds in MeOH-Wi corresponded with its antimicrobial activities against Micrococcus luteus NBRC 13867 (±11 mm), Candida maltosa NBRC 1977 (±9 mm), and Escherichia coli JM 109 (±5 mm) which were higher than the other tested extracts. Further purification using HPLC RP-C18 using NP-SiO2/n-Hex–EtOAc (10:2) to yield compound (1). Compound (1) was determined as an analog of briarian W—a diterpene mostly found in marine sponge, Briareum spp.—as a pure compound in the MeOH extract of H. monticulosa based on the 1D and 2D NMR analysis. The anticancer activity (IC50) of compound (1) was 0.077, 0.080, and 0.102 µg/mL against the growth of HCT-116, NBT-T2, and Panc-1, respectively. As far as we are aware, this is the first report on finding a briarian diterpene that originates from an endophytic fungus, especially by H. monticulosa.

Folic acid and ferritin functionalized reduced Iron-based metal-organic frameworks for anticancer therapy

Anticancer chemotherapies damage normal tissues and various drug carriers are under consideration to address this issue. Metal-organic frameworks (MOFs) are promising due to their drug-carrying capacity and tunable properties and target-inspired surface functionalization magnify their potential. In this study, we aim to investigate the anticancer activity of reduced iron-based MOFs (FeMOFs) functionalized with ferritin and folic acid and loaded with doxorubicin. Successful synthesis and functionalization are confirmed by Electron microscopes, Fourier transform infrared spectroscopy and X-ray diffraction. Anticancer activity is evaluated in different tumor cell lines at various doses. Results indicate that the folic acid functionalized MOF (FADMOF) showed maximum anticancer potential, leaving only 6 % of 4 T1 cells alive at the highest dose. While Ferritin and combo MOFs followed closely followed, and empty MOFs (RMOF) lagged. Further, in HeLa cells, the plain MOF (RMOF) shows best cytotoxicity reducing cell viability to a mere 30 % at the highest dose. Similarly, in MCF7 cells, the plain MOF (RMOF) shows best cytotoxicity reducing cell viability to a mere 25 % at the highest dose in a dose-dependent manner. Taken together, this study shows that functionalized MOFs have promising anticancer potential across various cancer cell lines. However, loading with Doxorubicin reduces their cytotoxicity.

Design of Bionanomaterial of Chitosan Carbohydrate Polymer Composited with Broccoli Extract and Zinc Oxide Nanoparticles: Anticancer Activity in Human Osteosarcoma.

In the current research, a chitosan/broccoli extract/ZnO nanoparticle (CH/BE/ZnO) bionanocomposite was created. The physicochemical properties of CH/BE/ZnO bionanocomposite were investigated using a variety of methods, including field emission scanning electron microscopy (FESEM), elemental analysis (CHN-O), X-ray diffraction (XRD), Fourier transform infrared spectrum (FTIR), Brunauer-Emmett-Teller (BET), and transmission electron microscopy (TEM). The CH/BE/ZnO bionanocomposite's biological activity was assessed by examining its cytotoxicity capabilities against a bone cancer cell line (MG63). The total pore volume and specific surface area of CH/BE/ZnO are 0.134 cm3/g and 16.99 m2/g, respectively. The IC50 results for CH/BE/ZnO bionanocomposite in bone cancer investigations using the MTT test against the MG63 cell line was 115μg/mL. The results indicate that the CH/BE/ZnO bionanocomposite is an effective chemotherapeutic agent against human osteosarcoma. The CH/BE/ZnO bionanocomposite showed high performance and structure, which means innovating nanomaterial agents for biological applications in the future.

Synthesis and Evaluation of amyloid beta peptide/ Ruthenium III -based complex drugs as drug delivery and anticancer activity

The development and characterization of anticancer complex drugs (ACD), specifically Amyloid Beta Peptide (ABP) - Ruthenium III (Ru III) - nivolumab (NB), were explored through analytical techniques. Fourier-transform infrared (FTIR) spectroscopy demonstrated the structural transformation of peptides from α-helical to β-sheet formations, aligning with amyloid fibril aggregation. Ruthenium (III) complex synthesis was confirmed through distinct absorption peaks in FTIR analysis. High-resolution scanning electron microscopy (HRSEM) revealed the fibrous and smooth morphology of ACD, while thermogravimetric analysis (TGA) confirmed the decomposition stages and stability of the ruthenium complexes. The encapsulation efficiency and in vitro release profile of nivolumab (NB) within ABP-RuIII-NB were investigated, showing a two-phase release over 40h. Cytotoxicity studies using acridine orange and ethidium bromide staining techniques indicated significant apoptosis in human oral squamous cell carcinoma (OSCC) -treated cells. These findings highlight the potential of ABP-RuIII-NB as an effective cancer treatment with controlled drug release and high cytotoxicity against cancer cells.

Downregulation of chemokine (C‑C motif) ligand 5 induced by a novel 8‑hydroxyquinoline derivative (91b1) suppresses tumor invasiveness in esophageal carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a particularly aggressive form of cancer with high mortality. In the present study, a novel 8‑hydroxyquinoline derivative (91b1) was investigated for its anticancer activities in ESCC along with its associated mechanisms. The in vitro cytotoxic effect of 91b1 were evaluated across five ESCC cell lines using MTS assay, with cisplatin serving as a comparative standard. Changes in gene expression profile were identified by cDNA microarray and further validated by qualitative PCR and immunostaining. Additionally, protein levels of the most notably downregulated target in archival ESCC samples were also studied. 91b1 demonstrated comparable anticancer effect with cisplatin. Notably, chemokine ligand 5 (Ccl5) was identified as the most substantially downregulated gene, with its suppression at both mRNA and protein expression in ESCC cells, exhibiting a dose‑dependent manner. The recombinant human protein of CCL5 enhanced the invasion of ESCC cells using the Transwell assay. The upregulation of CCL5 protein was also detected in 50% of ESCC cell lines. CCL5 was also overexpressed in 76.9% of ESCC specimens. The overall results indicated that 91b1 could effectively induce anticancer effect on ESCC cells through downregulating CCL5 expression with suppression of tumor invasion. Overall, these findings suggested that 91b1 effectively inhibited ESCC cell proliferation and tumor invasion by downregulating CCL5 expression, highlighting its potential as a therapeutic agent for ESCC treatment.

Curcuminoid Chalcones: Synthesis and Biological Activity against the Human Colon Carcinoma (Caco-2) Cell Line.

There are many current scientific reports on the synthesis of various derivatives modelled on the structure of known small-molecular and natural bioactive compounds. Curcuminoid chalcones are an innovative class of compounds with significant therapeutic potential against various diseases and they perfectly fit into the current trends in the search for new biologically active substances. The aim of this study was to design and synthesise a series of curcuminoid chalcones. The objective of this scientific paper was to synthesise twelve curcuminoid chalcones and confirm their structures using spectral methods. Additionally, the biological activity of three of the synthesised compounds was evaluated using various assays, and their anticancer properties and toxicity were studied. The proposed derivatives were obtained via the Claisen-Schmidt reaction of selected acetophenones and aldehydes in various conditions using both classical methods: the solutions and solvent-free microwave (MW) or ultrasound (US) variants. The most optimal synthetic method for the selected curcuminoid chalcones was the classical Claisen-Schmidt condensation in an alkaline (NaOH) medium. Spectral methods were used to confirm the structures of the compounds. The resazurin reduction assay, caspase-3 activity assay, and RT-qPCR method were performed, followed by measurements of the intracellular reactive oxygen species (ROS) level and the lactate dehydrogenase (LDH) release level. Twelve designed curcuminoid chalcones were successfully synthesized and structurally confirmed by NMR, MS, and IR spectroscopy. Examination of the anticancer activity was carried out for the three most interesting chalcone products. The results suggested that compound 3a increased the metabolism and/or proliferation of the human colon carcinoma (Caco-2) cell line, while compounds 3b and 3f showed significant toxicity against the Caco-2 cell line. Overall, the preliminary results suggested that compound 3b exhibited the most favourable anticancer activity.

Decreased mitochondrial translation confers 3,3′-Diindolylmethane resistance to Schizosaccharomyces pombe

3,3′-Diindolylmethane (DIM), a compound derived from natural fruits and vegetables, is widely recognized for its anti-cancer activity. However, its action mechanisms remain ambiguous. In this study, to study the molecular mechanism of 3,3′-Diindolylmethane, we identified a novel mutation in the gene of mitochondrial translation elongation factor EF-Ts (tsf1+), a key factor in mitochondrial protein translation, that conferred DIM resistance to Schizosaccharomyces pombe. The tsf1Δ also conferred DIM resistance. Decreased mitochondrial translation was found to be responsible for conferring DIM resistance to Schizosaccharomyces pombe, as the cells gained DIM resistance after treatment with chloramphenicol, a specific mitochondrial translation inhibitor. Notably, tsf1Δ conferred DIM resistance in the absence of either autophagy-related protein, Atg7, or nuclear envelope protein, Lem2, two proteins that have been reported to be required for cell survival in the presence of DIM. Overall, this study revealed novel biological functions of DIM and highlighted its potential as an anti-cancer agent.

Synthesis, characterization and biological studies of transition metal complexes of dehydroacetic acid Schiff bases derived from 3-aminomethyl pyridine

The solid metal complexes of Cu (II), Ni (II), Fe (III), Co (II), Mn (II) and Cd (II) with DHA Schiff base ligand derived from DHA and aromatic primary amine 3-aminomethyl pyridine were synthesized and characterized by elemental analysis, spectroscopic techniques (FTIR, UV-VIS, 1HNMR and XRD), magnetic susceptibility measurement, thermogravimetric analysis and differential thermal analysis (TGA/DTA) and investigated for biological activities like anti-bacterial, ant-fungal, antioxidant and anticancer activity. The structure of synthesized DHA Schiff base ligand and all metal complexes were confirmed by spectroscopic methods, stability of complexes was studied by TGA/DTA. DHA Schiff base ligand and all metal complexes were found to be biologically active.

Picoplatin (II)-loaded chitosan nanocomposites as effective drug delivery systems: Preparation, mechanistic investigation of BSA/5-GMP/GSH binding and biological evaluations

The goal of the current study is to improve the characteristics and bioavailability of the drug picoplatin (PPt) by encapsulating it in chitosan nanoparticles (CS NPs) which allows for the targeted delivery of cytotoxic cargo to cancerous tissue, reducing toxic side effects and raising the therapeutic index. When picoplatin was delivered into the CS, it was able to produce an complex with CS (PPt@CS NPs) that had an appropriate particle size of 275 ± 10 nm, a reasonably low PDI of 0.15 ± 0.05, and high stability (ζ = −22.1 ± 0.3 mV). Since almost all pharmaceuticals work by binding to specific proteins or DNA, the in vitro binding mechanism and affinity of bovine serum albumin (BSA), low molecular building units of nucleic acids (5−GMP), and Glutathione (GSH) (considering that cisplatin resistance could be due to a reaction between cisplatin and GSH) to PPt and PPt@CS NPs were examined using stopped-flow and other spectroscopic approaches. Through two reversible processes, a rapid second-order binding followed by a slower first-order isomerization reaction, and a static quenching mechanism, PPt and PPt@CS NPs bind to BSA with relative reactivity of around (PPt)/(PPt@CS NPs) = 1/2.5. The 5−GMP interaction studies demonstrated that, in addition to changing the binding mechanism, PPt's encapsulation in CS increases its rate of reaction through coordination affinity. PPt interacted with 5-GMP via two reversible processes, a rapid second-order binding to phosphate followed by a slower first−order migration to the N7 of pyrimidine moiety. PPt@CS NPs showed weaker binding to GSH compared to PPt and hence PPt@CS NPs exhibits a lower resistance factor. It was also found that the in vitro drug release of PPt@CS NPs in PBS at pH 7.4 was steady, releasing 30% of the PPt in just 5 hours. Nonetheless, 75% of the release in a pH 5.4 solution containing 10 mM GSH—a solution that mimics the tumor microenvironment—shows that the PPt@CS NPs system is sensitive to GSH and specifically targets malignant tissue. The encapsulation of PPt in CS complex maintained its anticancer activity, as shown by an in vitro cell-survival assay on HepG2 cancer cell lines and also cleavage efficiency toward the minor groove of pBR322 DNA via the hydrolytic way. These findings collectively suggested that inclusion PPt in CS would be an effective strategy to formulate a novel picoplatin formulation intended for use as targeted anticancer treatment.

A Novel Phytocolorant, Neoxanthin, as a Potent Chemopreventive: Current Progress and Future Prospects.

Cancer is a general term for a group of similar diseases. It is a combined process that results from an accumulation of abnormalities at different biological levels, which involves changes at both genetic and biochemical levels in the cells. Several modifiable risk factors for each type of cancer include heredity, age, and institutional screening guidelines, including colonoscopy, mammograms, prostate-specific antigen testing, etc., which an individual cannot modify. Although a wide range of resources is available for cancer drugs and developmental studies, the cases are supposed to increase by about 70% in the next two decades due to environmental factors commonly driven by the way of living. The drugs used in cancer prevention are not entirely safe, have potential side effects and are generally unsuitable owing to substantial monetary costs. Interventions during the initiation and progression of cancer can prevent, diminish, or stop the transformation of healthy cells on the way to malignancy. Diet modifications are one of the most promising lifestyle changes that can decrease the threat of cancer development by nearly 40%. Neoxanthin is a xanthophyll pigment found in many microalgae and macroalgae, having significant anti-cancer, antioxidant and chemo-preventive activity. In this review, we have focused on the anti-cancer activity of neoxanthin on different cell lines and its cancer-preventive activity concerning obesity and oxidative stress. In addition to this, the preclinical studies and future perspectives are also discussed in this review.

Biological active compounds from edible mushroom: Effect on hela cells

Background: Mushrooms are unique organisms rich in proteins, carbohydrates, vitamins, and minerals, which allows them to be used not only as a source of nutrition but also in cosmetics and medicine. The fungus P. ostreatus possesses two strong enzymatic complexes – lignin-decaying and cellulose-decaying. Objective: The research aimed to study the antitumor activity of treated mm-wave mycelial extracts of mushrooms on the HeLa cell line. Research on edible mushrooms against tumors is very actual and important for the field of functional food science and bioactive compounds field. Methods: The effect of the fungal culture extract on the cyto-photometric and morphometric indices of the HeLa cell line culture was studied according to the nature of proliferation and transcription of malignant tissues. Using high-resolution liquid chromatography, the amino acid composition of acid-soluble proteins in mycelial extracts of a mushroom culture treated with mm waves was studied. Results: Extracts of P. ostreatus mycelial culture significantly suppressed the growth of proliferative activity of human tumor cultures and completely suppressed the mitotic activity of continuous HeLa cell cultures to 72 hours. Our study revealed a significant increase in glutamic and aspartic acids in mycelial culture extracts treated by mm-waves. Conclusion: Based on HPLC analysis, we suggest polyfunctional peroxidase as the candidate for the role of biologically active compound in the composition of aqueous extracts of the mycelial culture. So, the polyfunctional peroxidase plays an active role in the therapeutic properties of the oyster mushroom. Keywords: anticancer activity, ant-inflammation activity, mm-waves, mushroom`s, mycelial extracts, HPLC of acid-soluble proteins, HeLa cell line.

Computational investigation of Pluchea indica mechanism targeting peroxisome proliferator-activated receptor gamma

Introduction: Pluchea indica is known to have diverse pharmacological properties, including anti-inflammatory, antioxidant, antimicrobial, and anticancer activities. However, there is a pressing need to thoroughly investigate the molecular interactions between P. indica compounds and peroxisome proliferator-activated receptor gamma (PPARG). This study aimed to elucidate the molecular mechanisms behind P. indica and PPARG, and its potential implications for diabetes mellitus. Methods: The computational investigation employed Pharmacological Network pharmacology, homology modeling, deep learning docking, and molecular dynamics to explore the active compounds and targets within P. indica against the PPARG. Results: Three active compounds were identified namely pinoresinol, syringaresinol, and plucheoside A, all of which complied with the Lipinski rule of five. The deep learning-based pose scores were determined as follows: Pinoresinol 0.55, syringaresinol 0.32, and plucheoside A 0.44. Additionally, protein-protein interactions were observed with PPARG and associated with the PPAR signaling pathway. Molecular dynamics simulation analysis showed the stability of the three compounds over a 100 ns period. Free energy calculations using Molecular Mechanics-Generalized Born and Surface Area (MM-GBSA) yielded ΔG values of -44.39 kcal/mol, -51.83 kcal/mol, and -40.27 kcal/mol for pinoresinol, syringaresinol, and plucheoside A, respectively. Conclusion: Pluchea indica might be developed to treat various diseases, particularly those involving the PPARG signaling pathway. It suggests the possibility of being developed as a focused medication for diabetes.

Yes-associated protein indispensably mediates hirsutine-induced inhibition on cell growth and Wnt/β-catenin signaling in colorectal cancer

Background and purpose: Targeting Wnt/β-catenin signaling emerges as one of the promising strategies for colorectal cancer (CRC) treatment, as this signaling is highly activated in CRC progression. Despite reports on the cytotoxic effects of hirsutine (HT), an indole alkaloid found in herbal medicines from the genus Uncaria, its therapeutic potential for CRC and the involved mechanisms are poorly understood. This study investigates the anticancer efficacy and the probable mechanisms of HT against CRC. Methods: To evaluate in vitro anticancer activity of HT, cell growth examined by MTT and colony formation assay, and apoptosis examined by flow cytometry were performed. To explore the mechanisms, RNA-sequencing, western blotting, dual-luciferase reporter assays, immunofluorescence, and co-immunoprecipitation were performed. Mouse model of azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colon cancer was utilized to assess HT's in vivo anticancer efficacy. Results: HT significantly inhibited CRC cell proliferation with IC50 values of 22.25 ± 3.27 μM for SW620 cells and 22.24 ± 2.36 μM for HCT116 cells, and induced apoptosis. HT decreased protein levels of Wnt3a and β-catenin dose- and time-dependently, and inhibited TOP/FOP FLASH reporter activity, nuclear travel of β-catenin, and downstream targets like c-Myc, Cyclin D1, VEGF. HT reduced β-catenin protein half-life, and the reversal of this effect by MG132 indicated that HT facilitated proteasome-dependent degradation of β-catenin in these two cell lines. HT also increased β-catenin ubiquitination without affecting Axin and β-TrCP levels. HT treatment for 24 h induced YAP cytoplasmic retention, enhanced YAP interacting with β-catenin and β-TrCP, triggering destruction complex formation and β-catenin ubiquitination and degradation, while YAP siRNA impaired these effects. Additionally, β-catenin overexpression and LiCl treatment counteracted HT-induced inhibition on cell growth and Wnt/β-catenin cascade. In model of AOM/DSS-induced mouse colon cancer, compared with AOM/DSS treatment group, HT recovered colon length, reduced tumor numbers and radius, and downregulated β-catenin and Ki-67, while upregulated cleaved PARP in the colorectal tissue with tumors. Conclusion: HT exhibits anticancer activity against CRC probably by inhibiting Wnt/β-catenin signaling, with YAP playing an indispensible role during the process, highlighting HT as a potential novel candidate drug for CRC therapy.