Potent Anticancer Potential Research Articles

Garcinol, a natural benzophenone overcomes radio and chemoresistance by targeting PI3K-PKB/AKT pathway in rhabdomyosarcoma cells

AKT signaling pathway is a critical intracellular signaling pathway involved in regulating various cellular processes, including cell proliferation, cell survival, cell migration and metabolism. Cancer cells have a propensity to alter the expression of pro- and anti-angiogenic signals to activate the angiogenic switch. Aberrant overexpression of AKT pathway is associated with various types of cancers and enables the migration and invasion of tumor cells to neighboring tissues. Garcinol, a natural benzophenone, displays potent anticancer potential against various cancer cells, but its mechanism of action in inducing apoptosis remains unclear. The present study aimed to unveil the mechanism of action of garcinol in inducing apoptosis in rhabdomyosarcoma cells. Garcinol inhibited cell proliferation, reduced the viability of cancer cells, diminished colony formation, and mitigated the migratory capabilities of Rh cells. In vitro analysis of garcinol unveiled potent anticancer and anti-metastatic activity, with an IC50 ranging from 5.32 to 16.28 against Rh cell lines, as demonstrated by MTT assay. Garcinol actuates apoptosis by triggering mitotic arrest (G2/M phase arrest) in Rh cell lines and alters the expression of pro-apoptotic and anti-apoptotic proteins to trigger efficient apoptosis in cancer cells.

Characterization and Bioactive Metabolite Profiling of Streptomyces sp. Y009: A Mangrove-Derived Actinomycetia with Anticancer and Antioxidant Potential.

Microorganisms from poorly explored environments are promising sources for the development of novel drugs. In our continuous efforts to screen for mangrove actinomycetes that produce metabolites with potential pharmaceutical applications, Streptomyces sp. Y009 was isolated from mangrove sediments in Guangxi, China. The phenotypic, physiological, biochemical, and phylogenetic characteristics of this strain were investigated. Analysis of phylogenetic and 16S rRNA gene sequences showed that it had the highest sequence similarity to Streptomyces thermolilacinus NBRC 14274 (98.95%). Further, the Y009 extract exhibited antioxidant activity, as indicated by DPPH and superoxide dismutase assays. The extract showed broad-spectrum and potent anticancer potential against six human cancer cell lines, with IC50 values ranging from 5.61 to 72.15 μg/mL. Furthermore, the selectivity index (SI) demonstrated that the Y009 extract exhibited less toxicity toward normal cell lines in comparison to the lung cancer cell line (A549) and hepatoma cell line (HepG2). GC-MS analysis revealed that the extract contained some biologically important secondary metabolites, mainly cyclic dipeptides and esters, which might be responsible for the antioxidant and anticancer properties. 3-Isobutylhexahydropyrrolo[1,2-a]pyrazine-1,4-dione (28.32%) was the major chemical compound available in the extract. The effect on cancer cells was then confirmed using nuclear staining and in silico docking. This study suggests that further exploration of the bioactive compounds of the newly isolated strain may be a promising approach for the development of novel chemopreventive drugs.

PH-tailored delivery of a multitarget anticancer benzimidazole derivative using a PEGylated β-cyclodextrin-curcumin functionalized nanocomplex

In this study, we aimed to enhance the bioavailability of a benzimidazole derivative with potent anticancer potential through a nano-based approach. Benzimidazole-loaded polyethylene glycol-β-cyclodextrin–functionalized curcumin nanocomplex (BMPE-Cur) was prepared and characterized for its physicochemical properties and drug release profiles under different pH conditions. In addition, the biological activities of the nanocomplex including antioxidant potentials and pro-apoptogenic properties, against HepG2, PC3, and the chemo-resistant MCF-7-ADR cell lines relative to the normal Wi-38 cell line were in vitro assessed and compared with those of the free benzimidazole compound. In addition to FTIR, XRD, and NMR spectral studies, a polymeric nanocomplex with an average particle size of 467.7 nm and high stability was successfully developed, as indicated by the negative zeta potential (−28.24 mV). The nanocomplex also showed prolonged pH-sensitive sustained drug release under conditions that replicated the tumor's extra/intracellular pH. The formulated nanocomplex also demonstrated potent radical scavenging capacity owing to the inclusion of curcumin, a known radical quencher. In addition, compared with the free compound, BMPE-Cur induced DNA fragmentation-driven cell cycle arrest in HepG2, PC3, and MCF-7-ADR cells at the G1/S, G1 & S phases; respectively, with remarkable selectivity. In conclusion, the newly formulated BMPE-Cur nanocomplex represents an attractive multitarget anticancer candidate.

Anticancer activity of Bacopa monnieri through apoptosis induction and mitophagy-dependent NLRP3 inflammasome inhibition in oral squamous cell carcinoma

BackgroundBacopa monnieri (BM) is traditionally used in human diseases for its antioxidant, anti-inflammatory and neuroprotective effects. However, its anticancer potential has been poorly understood. AimThe aim of this study was to explore the detailed anticancer mechanism of BM against oral cancer and to identify the bioactive BM fraction for possible cancer therapeutics. ResultsWe performed bioactivity-guided fractionation and identified that the aqueous fraction of the ethanolic extract of BM (BM-AF) had a potent anticancer potential in both in vitro and in vivo oral cancer models. BM-AF inhibited cell viability, colony formation, cell migration and induced apoptotic cell death in Cal33 and FaDu cells. BM-AF at low doses promoted mitophagy and BM-AF mediated mitophagy was PARKIN dependent. In addition, BM-AF inhibited arecoline induced reactive oxygen species production in Cal33 cells. Moreover, BM-AF supressed arecoline-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation through mitophagy in Cal33 cells. The in vivo antitumor effect of BM-AF was further validated in C57BL/6J mice through a 4-nitroquinolin-1-oxide and arecoline-induced oral cancer model. The tumor incidence was significantly reduced in the BM-AF treated group. Further, data obtained from western blot and immunohistochemistry analysis showed increased expression of apoptotic markers and decreased expression of inflammasome markers in the tongue tissue obtained from BM-AF treated mice in comparison with the non-treated tumor bearing mice. ConclusionIn conclusion, BM-AF exhibited potent anticancer activity through apoptosis induction and mitophagy-dependent inhibition of NLRP3 inflammasome activation in both in vitro and in vivo oral cancer models. Moreover, we have investigated apoptosis and mitophagy-inducing compounds from this plant extract having anticancer activity against oral cancer cells.

In vitro anti-cancer activity of a polyherbal preparation, VEDICINALS®9, against A549 human lung adenocarcinoma cells

PurposeNon-small cell lung cancer (NSCLC) is among the leading causes of morbidity and mortality worldwide. Despite the availability of several treatment options, the five-year survival rate of NSCLC is extremely low (<20%). This underlines the necessity of more effective therapeutic alternatives. In this context, plant-derived extracts and bioactive molecules extracted from plants, known collectively as phytoceuticals, represent an extremely variegated source of bioactive compounds with potent anticancer potential. In the present study, we tested the in vitro anticancer activity of a polyherbal preparation, VEDICINALS®9, containing nine different bioactive principles extracted by medicinal plants. MethodsThe anticancer activity of VEDICINALS®9 was investigated by measuring its impact on A549 human NSCLC cell proliferation (MTT assay and trypan blue staining), migration (wound healing assay and transwell chamber assay) and by measuring the impact on the expression of cancer-related proteins (Human XL Oncology Protein Array). ResultsWe show that VEDICINALS®9 at a concentration of 0.2% v/v has potent anticancer effect, significantly inhibiting A549 cell proliferation and migration. Mechanistically, this was achieved by downregulating the expression of proteins involved in cancer cell proliferation (Axl, FGF basic, enolase 2, progranulin, survivin) and migration (Dkk-1, cathepsins B and D, BCL-x, amphiregulin, CapG, u-plasminogen activator). Furthermore, treatment with VEDICINALS®9 resulted in increased expression of the oncosuppressor protein p53 and of the angiogenesis inhibitor endostatin. ConclusionsTaken together, our results provide proof of principle of the potent anticancer activity of the polyherbal preparation VEDICINALS®9, highlighting its enormous potential as an alternative or adjuvant therapy for lung cancer.

Protective Effects of Pelargonidin against DMBA-Induced Mammary Tumorigenesis in BALB/c Mice through Reduced Oxidative Stress and Lipid Anomalies

Among luminal types of breast cancers, ER + breast cancer is the most frequently diagnosed cancer globally. ER + breast cancer is commonly treated with SERM drugs that block ER to prevent ER-mediated cancerous growth. Our previous computational screening found pelargonidin (PG) can inhibit ER-signaling with potent bioactivity and satisfactory toxicological features. The present study explored the anti-tumoral prospect of PG against DMBA-induced ER + murine mammary carcinogenesis. The female BALB/c mice were divided into control (A) and DMBA-exposed groups. Following tumor appearance, the DMBA-exposed group was divided into five groups: tumor control, PG-treated (Groups P25, P50, and P100), and tamoxifen-treated (TAM). The results indicated that PG-treatment dose-dependently reduced the mean tumor volume, reinstated body weight loss, and enhanced the percentage survival of tumor-bearing mice. In addition, we recorded a significant reduction in LPO, total cholesterol, and triglycerides and a surge in the activity of antioxidases and phase II detoxifying enzymes in PG-treated animals. PG also dose-dependently increased the serum level of unbound estradiol, an indicator of competitive ER binding by an ER agonist/antagonist. These data suggest that pelargonidin has potent anticancer potential against the animal model of ER + breast cancer that matches the efficiency of tamoxifen with conceivably fewer side effects.

Co-drug development of gallic acid and metformin targeting the pro-inflammatorycytokines for the treatment of breast cancer.

It is well-documented that pro-inflammatory cytokines and inflammation play a significant role in the expansion of cancer disease. Gallic acid (GA), a natural compound, and metformin (Met), a synthetic drug exhibit potent anticancer potential via the distinct molecular mechanism. However, whether both these compounds can act synergistically to preclude and treat cancer is still unknown. This prompted us to scrutinize, the synergism between GA and Met, and that of a new co-drug synthesizing of GA and Met (GA-Met) and investigated the chemo-protective effect against breast cancer with possible intervention of cytokines. In vivo studies were based on chemical carcinogenesis, challenging breast tissue by dimethylbenz[α]anthracene (DMBA). Tumour incidence, tumour burden, pro-inflammatory cytokines in serum, breast, hepatic tissue, macroscopically and histological analysis of mammary tumours were carried out and estimated. GA, Metand GA-Met co-drug exhibited the inhibition of cell proliferation; higher reduction of cell proliferation was observed by GA-Met. The inhibitory effect of GA-Met was linked to cell cycle arrest at G0/G1 phase, along with induction of apoptosis and accumulation in the sub-G1 phase. GA-Met significantly inhibited the cytokines production along with protection against DMBA-induced hyperplasia. Taken altogether, the current result suggests that GA-Met co-drug endows a safe and protective effect against cancer metastasis and can possibly use for the treatment of human breast cancer.

Green Synthesized Zinc Oxide Nanoparticles induced Apoptosis in Human Cervical (HeLa) and Breast (MCF-7) Cancer Cell Lines

Chemotherapeutic resistance is currently one of the most prevalent problems due to the low absorption and undesirable toxicity of existing medications. Furthermore, non-specific targeting of existing medications is leading to the investigation of novel drug manufacturing strategies to eradicate chronic disorders. Present studies were performed to explore the anti-proliferative potential of synthesized zinc oxide nanoparticles (ZnO NPs) in human breast (MCF-7), human lung (A549) and human cervical (HeLa) cancer cell lines. The ZnO NPs were synthesized by using soybean seed extract. The ZnO NPs were characterized by ultraviolet-visible (UV-Vis) spectroscopy, field-emission scanning electron microscope (FESEM) and X-ray diffraction (XRD). The phytochemicals present in the soybean seed extract was evaluated using gas chromatography-mass spectroscopy (GC-MS) technique. Cytotoxicity effects of ZnO NPs, levofloxacin (LVX) and a combination of ZnO NPs-LVX against MCF-7, A549 and HeLa cancer cell lines was evaluated by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2Htetrazolium bromide (MTT) assay. Annexin assays were performed to explore the apoptosis-inducing potential of ZnO NPs and its drug combination. This showed that tested compounds have potent cytotoxic effects dose-dependently against cancer cell lines. The potent anticancer potential of ZnO NPs-LVX is expressed to utilize in the near future as novel therapeutic strategies.

Therapeutic potential and bioactive phenolics of locally grown Pakistani and Chinese varieties of ginger in relation to extraction solvents

Current study compares the Therapeutic/nutra-pharmaceuticals potential and phenolics profile of Pakistani grown Pakistani and Chinese varieties of ginger. Crude yield of bioactive components from the varieties tested, using different extraction solvents including chloroform, ethyl acetate, ether, methanol, ethanol and distilled water. The crude bioactives varied from 14.1-82.5%. The highest extraction yield was noted for Pakistani species. The HPLC analysis revalued significant amounts of phenolics including vanillin, protocatechuic, vanillic, ferulic, sinapinic and cinnamic acids. The highest anti-inflammatory activity was shown by ethanolic extract of Pakistani variety (IC50: 26.5±1.8) whereas Chinese variety exhibited potent anticancer potential against MCF-7 cell line (Inhibition: 91.38 %). The Chinese variety in general showed higher phenolics and anticancer, while the Pakistani exhibited higher anti-inflammatory activity. Pakistani grown ginger and ethanolic extract of Chinese ginger showed highest antimicrobial activity against Pseudomonas aeruginosa 18.0±0.02 & 15.00±0.02 mm respectively. Minimum results obtained with water for both varieties of ginger with range of 7.2±0.22 and 6±0.07 respectively. Moreover, the phenolics composition, anti-inflammatory, antibacterial and anticancer activities of both tested varieties of ginger were notably affected as a function of extraction solvents. Our findings advocate selection of appropriate solvent for recovery of effective phenolic bioactive compounds from ginger verities to support the Nutra-pharmaceutical formulation.

Proteomic profiling the molecular signatures of plectranthoic acid in prostate cancer cells

Among cancers, prostate cancer (PCa) is frequently detected solid tumor and a growing problem for the male population, globally. Newer treatment modalities with specific targets are required for management. Plant-derived agents/drugs have historically been useful in cancer therapeutics. Natural metabolite i.e. plectranthoic acid (PA), inhibits the proliferation of PCa cells and has potent anti-cancer potential. Herein, we aim to identify the molecular signatures of PA. Proteins from control and PA-treated PCa cells were analysed using high-throughput labeled free proteomics approach. Data was processed with the SIEVE software and thoroughly analysed by using Ingenuity pathway analysis (IPA) and PANTHER. A total of 98 unique peptides, showing >2 fold change, were identified. Results indicated that PA modulates oncogenic pro-survival and pro-apoptotic signaling pathways in PCa cells. mTOR was the major canonical pathway targeted by PA, the inhibition of which was likely to induce PA mediated apoptosis. Moreover, PA interacts with the rapamycin binding domain of mTOR, demonstrated by the molecular dynamic (MD) simulation and binding free energy calculations. Furthermore, the biological process moderated by PA with a high percentage was a metabolic process. Taken together, PA appears to have pleiotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness. SignificanceStudies on the mechanism of action of therapeutic agents are crucial for drug development. These studies support the selection of a therapeutic agent, appropriate models of its efficacy, and designing of further experiments. Furthermore, information on mechanism of action may suggest strategies for combination therapies. In this regard Proteomics provide the platform for comprehensive understanding of the molecular action mechanisms of newly discovered therapeutic agents. Current research highlights the new insights into mode of action of novel therapeutic metabolite i.e. Plectranthoic acid (PA). Using labeled free proteomics approach we extracted the underlying mechanisms for the anticancer activity of PA using prostate cancer model. The result of the study will pay the way for further investigations on this potent natural compound in different cancers and will provide a root for its development as a lead.

Steroidal Pyrazolines As a Promising Scaffold in Drug Discovery

Steroidal pyrazolines constitute an interesting and promising scaffold for drug discovery as they display diverse chemical reactivity and a wide range of biological activities. Literature reports indicate potent anticancer potential of steroidal pyrazolines along with broad-spectrum antimicrobial activities. Strong neuroprotective effects with steroids possessing pyrazoline moiety have also been observed. Among all the therapeutically active steroidal pyrazolines, D-ring-substituted derivatives are highly potent and the least toxic. The current and futuristic research approaches in this area are focused towards the exploration of this promising scaffold to develop molecules with widespread pharmacological activities. This review article mainly covers the synthetic and pharmacological aspects of steroidal pyrazolines, which will assist the medicinal chemists working in this area in their scientific endeavors.

Comparative metabolite profiling of Callistemon macropunctatus and Callistemon subulatus volatiles from different geographical origins

Since ancient times, essential oils from medicinal plants have supplied a huge repository of secondary metabolites. Genus Callistemon, Myrtaceae, was described to have nematicidal, antithrombotic, antistaphylococcal, antioxidant, and insecticidal activities. In this study we investigate the chemical composition of essential oils from the leaves and the flowers of C. macropunctatus (Dum.Cours.) Court and Callistemon subulatus (Cheel) from two geographical locations: Australia and Egypt. GCMS analysis identified a total of sixty-one volatile components and showed that the major constituents were 1,8-cineole, α-pinene, α-terpineol, limonene and α-phellandrene in the leaves and α-pinene, 1,8-cineole, α-phellandrene, limonene and α-terpineol in the flowers of Callistemon species. To discriminate the oil complexity within factors as location, plant parts and species, principal component analysis (PCA) and hierarchical cluster analysis (HCA) were employed. Furthermore, the cytotoxic effect of the oil samples was assayed against the human liver cancer cell line HepG2 to reveal a potent anticancer potential with half-maximal inhibitory concentration (IC50) values ranging from 1.76 μg/mL to 13.41 μg/mL. To gain insight into the cellular mechanism of the cytotoxic activity, Callistemon volatile oils’ activities on topoisomerases I-β and II-β were explored, which demonstrated significant enzyme inhibition with IC50 values as low as 819.6 ng/mL. Molecular in-silico docking study of the major oil components within the active binding site of the human topoisomerases I-β and II-β was conducted. α-terpineol showed promising alkyl interactions in the binding pockets of topoisomerase IB and IIB, with a docking Gibb’s free energy values of -27.0913 and -26.6478 kcal/mol, respectively. Whereas it bounded to Arg503 and four nucleotide regions deoxyadenosine DA12, deoxythymidine DT9, deoxyguanosine DG13, deoxycytidine DC8 in the topoisomerase II-β enzyme pocket, it interacted with Topo I-β enzyme through hydrophobic alkyl and Pi-alkyl binding interactions with DA12, DG13 and Arg503. Furthermore, the oxygen in the hydroxyl group showed two additional non-covalent bonds: a conventional hydrogen bond with Asp533 and water hydrogen bond with a water molecule in the vicinity of the binding surface. This research highlights the future possibility of having Callistemon subulatus as a potential natural drug for treatment of liver cancer.

A Marine-based Meriolin (3-Pyrimidinylazaindole) Derivative (4ab) Targets PI3K/AKT /mTOR Pathway Inducing Cell Cycle Arrest and Apoptosis in Molt-4 Cells

Background: Cyclin-dependent kinases play a central role in the control of cell division and therefore it is not surprising that cancer exhibits some features that disturb the normal controls over the cell cycle. Previous studies related to the development of 3-Pyrimidinylazaindole (Meriolin) derivatives as novel Cyclin dependent kinase inhibitors highlighted 4ab as the most potent inhibitor. Objective: The main objective of the current study was to understand the mode of cell death and the effect of 4ab on major cellular networking pathways in cancer. Method: Preliminary apoptotic studies were carried out using flowcytometer and electron microscope. The effect on cellular signalling was studied via western blotting. Results: 4ab was found to inhibit the enzymatic activity of CDK2. The inhibition of CDK2 activity was found to be associated with the down-regulation of P-cdc-25 and arrest of cells in G0-G1 phase of the cell cycle in lymphoblastic leukemia cells. Further, 4ab was found to affect AKT-mToR pathway by down-regulating the expression of major proteins including P-m-TOR (2448), P110α, P-AKT (S473) and P-p-70S6K. Conclusion: Current study shows that the potent anticancer potential of 4ab is mediated via cellular apoptosis, dysregulation of mitochondrial membrane potential and arrest of G1 phase in Molt-4 cells. Further, target-based studies showed the effect of 4ab on one of the major cellular signalling pathways deregulated in cancer.

Candelariella vitellina extract triggers in vitro and in vivo cell death through induction of apoptosis: A novel anticancer agent

Candelariella vitellina is common green-yellow lichen found on barks, wood, and rocks in Japanese forests. To investigate the mechanism of its anticancer potential, C. vitellina (80% MeOH/H2O) extract was prepared. High-performance liquid chromatography–high-resolution electrospray ionization mass spectrometry analysis revealed seven new compounds and 11 natural compounds of terpenes and polyketides. In vitro cytotoxicity analysis of Caco-2 cells exhibited an IC50 of 125 ± 4.1 μg/mL. No significant cytotoxicity was observed in vitro in normal human peripheral lymphocytes. Both the IC25 and IC50 were determined to explore the potent anticancer potential in this study. C. vitellina exhibited a mitochondrial P53-independent apoptotic effect with negative P53 expression and an elevated BAX/BCL2 ratio as well as upregulated CASP3 mRNA expression. Similarly, in vivo analysis showed the same pattern of anticancer potential but was dependent on the P53 expression. Furthermore, C. vitellina induced antioxidative conditions in vitro and in vivo. The decreased invasion of tumor cells in vivo and increased apoptotic features in vitro and in vivo suggest the moderate to strong apoptotic anticancer potential of C. vitellina. However, further studies are needed to determine the extent and mechanism of action on different cell lines to support the anticancer properties of this lichen.

Combination drug delivery via multilamellar vesicles enables targeting of tumor cells and tumor vasculature.

Blood vessel development is critical for the continued growth and progression of solid tumors and, therefore, makes an attractive target for improving cancer therapy. Indeed, vascular-targeted therapies have been extensively explored but they have shown minimal efficacy as monotherapies. Combretastatin A4 (CA-4) is a tubulin-binding vascular disrupting agent that selectively targets the established tumor endothelium, causing rapid vascular beak down. Despite its potent anticancer potential, the drug has dose-limiting side effects, particularly in the form of cardiovascular toxicity. Furthermore, its poor aqueous solubility and the resulting limited bioavailability hinder its antitumor activity in the clinic. To improve the therapeutic efficacy of CA-4, we investigated its application as a combination therapy with doxorubicin (Dox) in a tumor vasculature targeted delivery vehicle: peptide-modified cross-linked multilamellar liposomal vesicles (cMLVs). In vitro cell culture studies showed that a tumor vasculature-targeting peptide, RIF7, could facilitate higher cellular uptake of drug-loaded cMLVs, and consequently enhance the antitumor efficacy in both drug resistant B16 mouse melanoma and human MDA-MB-231 breast cancer cells. In vivo, upon intravenous injection, targeted cMLVs could efficiently deliver both Dox and CA-4 to significantly slow tumor growth through the specific interaction of the targeting peptide with its receptor on the surface of tumor vasculature. This study demonstrates the potential of our novel targeted combination therapy delivery vehicle to improve the outcome of cancer treatment.

MicroRNA profiling in MDA-MB-231 human breast cancer cell exposed to the Phaleria macrocarpa (Boerl.) fruit ethyl acetate fraction (PMEAF) through IIlumina Hi-Seq technologies and various in silico bioinformatics tools

Ethnopharmacological relevancePhaleria macrocarpa (Scheff) Boerl, is a famous traditional medicinal plant which exhibited cytotoxicity against various cancerous cells. Traditionally, P. macrocarpa has been used to control cancer, impotency, hemorrhoids, diabetes mellitus, allergies, liver and heart disease, kidney disorders, blood diseases, acne, stroke, migraine, and various skin diseases. Aim of the studyRecent studies have demonstrated a potent anticancer potential of P. macrocarpa, especially against HeLa cell. The objective of this study was to investigate the regulation of miRNAs on MDA-MB-231 treated with P. macrocarpa ethyl acetate fraction (PMEAF). Materials and methodsThe regulation of miRNAs on MDA-MB-231 cells treated with PMEAF was studied through IIlumina, Hi-Seq. 2000 platform of Next Generation Sequencing (NGS) and various in silico bioinformatics tools. ResultsThe PMEAF treatment against MDA-MB-231 cells identified 10 upregulated and 10 downregulated miRNAs. A set of 606 target genes of 10 upregulated miRNAs and 517 target genes of 10 downregulated miRNAs were predicted based on computational and validated databases by using miRGate DB Query. Meanwhile, results from DAVID Bioinformatics Resources 6.8 specified the functional annotation of the upregulated miRNAs involvement in cancer pathway by suppressing the oncogenes and downregulating miRNAs by expressing the tumour suppressor genes in the regulation of apoptosis pathway. ConclusionIn conclusion, the results of this study proved that PMEAF is a promising anticancer agent with high cytotoxicity against MDA-MB-231 breast cancer cells and it induced apoptotic cell death mechanism through the regulation of miRNAs. PMEAF might be the best candidate for developing more potent anticancer drugs or chemo preventive supplements.

A multi-target therapeutic potential of Prunus domestica gum stabilized nanoparticles exhibited prospective anticancer, antibacterial, urease-inhibition, anti-inflammatory and analgesic properties.

BackgroundPhytotherapeutics exhibit diverse pharmacological effects that are based on the combined action of a mixture of phytoconstituents. In this study, Prunus domestica gum-loaded, stabilized gold and silver nanoparticles (Au/Ag-NPs) were evaluated for their prospective anticancer, antibacterial, urease-inhibition, anti-inflammatory, and analgesic properties.MethodsAu/Ag-NPs were biosynthesized and characterized with UV-Vis, FTIR, SEM, EDX, and XRD techniques. The effect of gum and metal ion concentration, reaction temperature, and time on the synthetic stability of nanoparticles was studied along with their post-synthetic stability against varying pH and salt concentrations, long-term storage and extremes of temperature. Nanoparticles were tested for anticancer (HeLa cervical cancer cells), antibacterial (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa), urease inhibition (jack-bean urease), anti-inflammatory (carrageenan-induced paw edema), and antinociceptive (abdominal constriction response) activities.ResultsThe nanoparticles were mostly spherical with an average particle size between 7 and 30 nm (Au-NPs) and 5–30 nm (Ag-NPs). Au/Ag-NPs maintained their colloidal stability and nanoscale characteristics against variations in physicochemical factors. Au/Ag-NPs have potent anticancer potential (IC50 = 2.14 ± 0.15 μg/mL and 3.45 ± 0.23 μg/mL). Au/Ag-NPs selectively suppressed the growth of S. aureus (10.5 ± 0.6 mm, 19.7 ± 0.4 mm), E. coli (10 ± 0.4 mm, 14.4 ± 0.7 mm), and P. aeruginosa (8.2 ± 0.3 mm, 13.1 ± 0.2 mm), as well as showed preferential inhibition against jack-bean urease (19.2 ± 0.86%, 21.5 ± 1.17%). At doses of 40 and 80 mg/kg, Au-NPs significantly ameliorated the increase in paw edema during the 1st h (P < 0.05, P < 0.01) and 2–5 h (P < 0.001) of carrageenan-induced inflammation compared to the 200 and 400 mg/kg doses of P. domestica gum (P < 0.05, P < 0.001). At similar doses, Au-NPs also significantly abolished (P < 0.01) the tonic visceral, chemically-induced nociception, which was comparable to that of P. domestica gum (200 mg/kg; P < 0.05, 400 mg/kg; P < 0.01).

Screening of Chonemorpha fragrans Bioactive Extracts for Cytotoxicity Potential and Inhibition Studies of Key Enzymes Involved in Replication.

Background:Chonemorpha fragrans (Moon) Alston, a liana belonging to family Apocynaceae, is used in traditional medicinal systems for the treatment of various ailments. It is an unexplored medicinal plant with respect to its anticancer potential.Objective:Cytotoxicity of sequential as well as crude extracts of in vivo plant parts (leaves, bark, and roots), in vitro cultures, and callus were compared.Materials and Methods:3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay was used to compare the extracts of various in vivo plant parts (leaves, bark, and roots) along with in vitro culture systems (in vitro plantlets, callus). Furthermore, the extracts were used to evaluate inhibition of key enzymes involved in replication, i.e. topoisomerase (Topo) I and II, DNA polymerase, to check the probable mechanism of action for this cytotoxicity.Results:MTT assay showed that the chloroform extract of callus has potent anticancer potential. The plant has a promising anticancer activity against human colon epithelium, lung carcinoma, and epidermoidal carcinoma cell lines. It was found to possess Topo as well as DNA polymerase inhibitory activity.Conclusion:The results have pointed toward pharmaceutical importance of this plant. This study is the first report of exploring the antiproliferative potential as well as inhibition studies of key enzymes involved in replication, which was useful to point out probable mechanism of action for extracts of C. fragrans.SUMMARY It's a first report of cytotoxicity studies and inhibition of enzyme involved in the replication process by Chonemorpha fragrans plant extracts. The results reveal the pharmaceutical importance of this plant. From various assays performed here, a potent anticancer potential of chloroform extract of callus was revealed showing Topo I (E. coli and human) inhibitory activity, DNA pol inhibitory activity. Considering the importance of these activities, plant further needs to be explored in detail for in vivo cancer studies as well as for its metabolite content. Abbreviations used: CPT: Camptothecin, EDTA: Ethylenediaminetetraacetic acid, MTT: 3-4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide, Pol: Polymerase, Topo - Topoisomerase.

In search of natural remediation for cervical cancer.

Cancer is a serious global health issue. Cancer of the cervix is one of the leading gynecological malignancies worldwide; though it is more prevalent in the developing countries. Fruitful approaches are needed to control cervical cancer. Awareness through proper education, screening and early detection may pave a way to combat the disease process in the first place. Surgery, chemotherapy and radiotherapy are some of the common modes of treatment for cervical cancer. Conventional medical treatments often are not able to eliminate the offending growth fully and are not free from complications. Side effects very often are disastrous. Therefore, it is high time to focus our attention to bring about a novel way to tackle the problem. Advocating holistic approach using plant derived phytochemicals may address this health problem. These molecules show potent anticancer potential and are free from toxicity. Adjunctive therapies using phytochemicals may prove to be of tremendous importance. Plants are a prime source of effective drugs for the treatment of various forms of cancer. Many of these compounds are well characterized and have led the researchers to develop potential chemotherapeutic agents. Neutraceuticals may not replace the conventional treatment regimen, but they may enhance the efficacy of chemotherapy and radiotherapy.

Global Assessment of Antrodia cinnamomea-Induced MicroRNA Alterations in Hepatocarcinoma Cells

Recent studies have demonstrated a potent anticancer potential of medicinal fungus Antrodia cinnamomea, especially against hepatocarcinoma. These studies, however, were performed with prolonged treatments, and the early anticancer events remain missing. To probe the early anticancer mechanisms of A. cinnamomea, we treated SK-Hep-1 liver cancer cell with A. cinnamomea fruiting body extract for 2 and 4 hours, sequenced RNA samples with next-generation sequencing approach, and profiled the genome-wide miRNA and mRNA transcriptomes. Results unmistakably associated the early anticancer effect of A. cinnamomea fruiting body extract with a global downregulation of miRNAs which occurred solely in the A. cinnamomea fruiting body extract-treated SK-Hep-1 cells. Moreover, the inhibitory effect of A. cinnamomea fruiting body extract upon cancer miRNAs imposed no discrimination against any particular miRNA species, with oncomirs miR-21, miR-191 and major oncogenic clusters miR-17-92 and miR-106b-25 among the most severely downregulated. Western blotting further indicated a decrease in Drosha and Dicer proteins which play a key role in miRNA biogenesis, together with an increase of XRN2 known to participate in miRNA degradation pathway. Transcriptome profiling followed by GO and pathway analyses indicated that A. cinnamomea induced apoptosis, which was tightly associated with a downregulation of PI3K/AKT and MAPK pathways. Phosphorylation assay further suggested that JNK and c-Jun were closely involved in the apoptotic process. Taken together, our data indicated that the anticancer effect of A. cinnamomea can take place within a few hours by targeting multiple proteins and the miRNA system. A. cinnamomea indiscriminately induced a global downregulation of miRNAs by simultaneously inhibiting the key enzymes involved in miRNA maturation and activating XRN2 protein involved in miRNA degradation. Collapsing of the miRNA system together with downregulation of cell growth and survival pathways and activation of JNK signaling unleash the extrinsic and intrinsic apoptosis pathways, leading to the cancer cell death.