Anticancer Bioactivity Research Articles

Modulation of Bleomycin-induced Oxidative Stress and Pulmonary Fibrosis by Ginkgetin in Mice via AMPK.

Ginkgetin, a flavonoid extracted from Ginkgo biloba, has been shown to exhibit broad anti-inflammatory, anticancer, and antioxidative bioactivity. Moreover, the extract of Ginkgo folium has been reported on attenuating bleomycin-induced pulmonary fibrosis, but the anti-fibrotic effects of ginkgetin are still unclear. This study was intended to investigate the protective effects of ginkgetin against experimental pulmonary fibrosis and its underlying mechanism. In vivo, bleomycin (5 mg/kg) in 50 μL saline was administrated intratracheally in mice. One week after bleomycin administration, ginkgetin (25 or 50 mg/kg) or nintedanib (40 mg/kg) was administrated intragastrically daily for 14 consecutive days. In vitro, the AMPK-siRNA transfection in primary lung fibroblasts further verified the regulatory effect of ginkgetin on AMPK. Administration of bleomycin caused characteristic histopathology structural changes with elevated lipid peroxidation, pulmonary fibrosis indexes, and inflammatory mediators. The bleomycin- induced alteration was normalized by ginkgetin intervention. Moreover, this protective effect of ginkgetin (20 mg/kg) was equivalent to that of nintedanib (40 mg/kg). AMPK-siRNA transfection in primary lung fibroblasts markedly blocked TGF-β1-induced myofibroblasts transdifferentiation and abolished oxidative stress. All these results suggested that ginkgetin exerted ameliorative effects on bleomycininduced oxidative stress and lung fibrosis mainly through an AMPK-dependent manner.

Enhanced production of aspochalasin D through genetic engineering of Aspergillus flavipes.

Aspochalasin D (AD) belongs to the polyketide-amino acid hybrid natural products with anti-cancer, anti-bacterial, and anti-fouling bioactivities. However, the low production limits its further application. In this study, AD was separated and identified from Aspergillus flavipes 3.17641. Next, besides the optimization of culture conditions using a single-factor experiment and response surface methodology, metabolic engineering was employed to increase the AD production. It shows that the deletion of the shunt gene aspoA and overexpression of the pathway-specific regulator aspoG significantly improve the AD production. Its production reached to 812.1mg/L under the optimized conditions, with 18.5-fold increase. Therefore, this study not only provides a general method for improving the production of similar natural products in other fungi, but also enables the further biological function development of AD in agriculture and pharmaceutical. KEY POINTS: • The Aspochalasin D (AD) production was improved by optimizing culture conditions. • The deletion of the shunt gene aspoA increased the AD production. • Overexpression of the pathway regulator aspoG further improved the AD production.

NHC-gold(I)-alkyne complexes induced hepatocellular carcinoma cell death through bioorthogonal activation by palladium complex in living system

Bioorthogonal reactions can take place in biological environments without interfering with biochemical processes. In this study, Pd(PPh3)2Cl2 was used as a bioorthogonal catalyst to in situ transform the stable N-heterocyclic carbene (NHC)-gold(I)-alkyne complex 5 to its active species which can effectively inhibit thioredoxin reductase (TrxR) and exhibit significant anticancer bioactivity in hepatocellular carcinoma (HCC).

Network Analysis Reveals the Molecular Bases of Statin Pleiotropy That Vary with Genetic Background.

Many approved drugs are pleiotropic: for example, statins, whose main cholesterol-lowering activity is complemented by anticancer and prodiabetogenic mechanisms involving poorly characterized genetic interaction networks. We investigated these using the Saccharomyces cerevisiae genetic model, where most genetic interactions known are limited to the statin-sensitive S288C genetic background. We therefore broadened our approach by investigating gene interactions to include two statin-resistant genetic backgrounds: UWOPS87-2421 and Y55. Networks were functionally focused by selection of HMG1 and BTS1 mevalonate pathway genes for detection of genetic interactions. Networks, multilayered by genetic background, were analyzed for key genes using network centrality (degree, betweenness, and closeness), pathway enrichment, functional community modules, and Gene Ontology. Specifically, we found modification genes related to dysregulated endocytosis and autophagic cell death. To translate results to human cells, human orthologues were searched for other drug targets, thus identifying candidates for synergistic anticancer bioactivity. IMPORTANCE Atorvastatin is a highly successful drug prescribed to lower cholesterol and prevent cardiovascular disease in millions of people. Though much of its effect comes from inhibiting a key enzyme in the cholesterol biosynthetic pathway, genes in this pathway interact with genes in other pathways, resulting in 15% of patients suffering painful muscular side effects and 50% having inadequate responses. Such multigenic complexity may be unraveled using gene networks assembled from overlapping pairs of genes that complement each other. We used the unique power of yeast genetics to construct genome-wide networks specific to atorvastatin bioactivity in three genetic backgrounds to represent the genetic variation and varying response to atorvastatin in human individuals. We then used algorithms to identify key genes and their associated FDA-approved drugs in the networks, which resulted in the distinction of drugs that may synergistically enhance the known anticancer activity of atorvastatin.

Nano-Based Drug Delivery of Polyphenolic Compounds for Cancer Treatment: Progress, Opportunities, and Challenges.

Polyphenols and their derivates, a kind of natural product distributed in herb plants, vegetables, and fruits, are the most abundant antioxidants in the human diet and have been found to display cancer-preventative effects in several epidemiological studies. The scientific community has also validated the anti-cancer bioactivities and low toxicities of polyphenolic compounds, including flavones, tannins, phenolic acids, and anthocyanins, through in vitro and in vivo studies. However, the low stability, weak targeting ability, poor solubility, and low bioavailability of pure polyphenolic agents have significantly impaired their treatment efficacy. Nowadays, nano-based technology has been applied to surmount these restrictions and maximize the treatment efficacy of polyphenols. In this review, we summarize the advantages and related mechanisms of polyphenols in cancer treatment. Moreover, aiming at the poor solubility and low bioavailability of pure polyphenols in vivo, the advantages of nano-based delivery systems and recent research developments are highlighted. Herein, particular emphasis is mainly placed on the most widely used nanomaterials in the delivery of natural products, including liposomes, micelles, and nanogels. Finally, we present an overview and the challenges of future implementations of nano-based delivery systems of polyphenolic compounds in the cancer therapeutic field.

Research advances on endophytic fungi and their bioactive metabolites.

Endophytic fungi, as a kind of fungi living in the healthy plant tissues and organs, are important sources of natural bioactive products and new microbial resources with high developing value. Therefore, exploration and utilization of endophytic fungi can not only alleviate the problems of resource shortage and ecological balance destruction caused by extracting large number of useful bioactive products from natural plants, but also benefit the protection of rare and endangered plant resources, which is of great significance and economic value. This review mainly expounds the concept of endophytic fungi, analyzes the research advances of endophytic fungi from antioxidant, antibacterial, insecticidal, regulating plant growth, anticancer and antitumor bioactivities and, furthermore, summarizes the existing problems in present research of endophytic fungi and corresponding solutions. We hope that this review could provide references for the development and utilization of endophytic fungi and their bioactive metabolites.

Efficient Synthesis with Green Chemistry Approach of Novel Pharmacophores of Imidazole-Based Hybrids for Tumor Treatment: Mechanistic Insights from In Situ to In Silico.

Simple SummaryHere, we report the eco-friendly synthesis and antitumor potential of the imidazole hybrids of pyrimidine. The results showed that all the compounds possess excellent inhibition of tumors, promoting enzymes hCA-IX and hCA-II. Furthermore, the selectivity index showed that compounds 7, 10, and 11 are selective inhibitors of hCA-IX, while compound 2 is a selective inhibitor of hCA-IX. More importantly, all the active inhibitors are toxic to the breast cancer cell line and non-cytotoxic for the normal breast cell line. These compounds would be a suitable choice to investigate in the in vivo models to check their efficacy against these particular targets. These newly identified human carbonic anhydrase inhibitors have potential to be considered as therapeutic leads for the treatment of CA-related diseases, especially for breast and lung tumors and glaucoma. Furthermore, lead optimization and preclinical and clinical investigations of these compounds are necessary to develop potential drug entities for the treatment of cancer.Imidazole-based pyrimidine hybrids are considered a remarkable class of compounds in pharmaceutical chemistry. Here, we report the anticancer bioactivities of eleven imidazole-based pyrimidine hybrids (1–11) that specifically target cytosolic carbonic anhydrase (CAs) isoenzymes, including human CA-II and human CA-IX (hCA-II, and hCA-IX). A highly eco-friendly aqueous approach was used for the formation of a carbon–carbon bond by reacting aromatic nitro group substitution of nitroimidazoles with carbon nucleophiles. The in vitro results indicate that this new class of compounds (1–11) includes significant inhibitors of hCA IX with IC50 values in the range of 9.6 ± 0.2–32.2 ± 1.0 µM, while hCA II showed IC50 values in range of 11.6 ± 0.2–31.1 ± 1.3 µM. Compound 2 (IC50 = 12.3 ± 0.1 µM) showed selective inhibition for hCA-II while 7, 8, and 10 (IC50 = 9.6–32.2 µM) were selective for hCA-IX. The mechanism of action was investigated through in vitro kinetics studies that revealed that compounds 7, 3, 11, 10, 4, and 9 for CA-IX and 1, 2, and 11 for CA-II are competitive inhibitors with dissociation constant (Ki) in the range of 7.32–17.02 µM. Furthermore, the in situ cytotoxicity of these compounds was investigated in the human breast cancer cell line MDA-MB-231 and compared with the normal human breast cell line, MCF-10A. Compound 5 showed excellent anticancer/cytotoxic activity in MDA-MB-231 with no toxicity to the normal breast cells. In addition, in silico molecular docking was employed to predict the binding mechanism of active compounds with their targets. This in silico observation aligned with our experimental results. Our findings signify that imidazole-based hybrids could be a useful choice to design anticancer agents for breast and lung tumors, or antiglaucoma compounds, by specific inhibition of carbonic anhydrases.

Identification of Crucial Polymethoxyflavones Tangeretin and 3,5,6,7,8,3',4'-Heptamethoxyflavone and Evaluation of Their Contribution to Anticancer Effects of Pericarpium Citri Reticulatae 'Chachi' during Storage.

Pericarpium Citri Reticulatae ‘Chachi’ (PCR-C), rich in polymethoxyflavones (PMFs), has potential anticancer bioactivity and its quality will be improved during storage. However, the main factors influencing the PCR-C quality during its storage remain unclear. In this study, multivariate analysis was performed to investigate free and bound PMFs of PCR-C during storage. The anticancer effects of purified PCR-C flavonoid extracts (PCR-CF) and the important PMFs were evaluated using A549 cells. The results showed that PCR-C samples exhibited remarkable differences in free PMFs during storage, which fell into three clusters: Cluster 1 included fresh (fresh peel) and PCR-C01 (year 1); Cluster 2 consisted of PCR-C03 (year 3) and PCR-C05 (year 5); and PCR-C10 (year 10) was Cluster 3. 3,5,6,7,8,3′,4′-heptamethoxyflavone, tangeretin, and isosinensetin were identified as the most important PMFs distinguishing the various types of PCR-C according to its storage periods. Moreover, PCR-CF inhibited A549 cell proliferation and induced cell cycle arrest at G2/M phase, cell apoptosis, and ROS accumulation, and all anticancer indices had an upward tendency during storage. Additionally, tangeretin and 3,5,6,7,8,3′,4′-heptamethoxyflavone exhibited anticancer effects on A549 cells, whereas isosinensetin displayed no anticancer effect, indicating that tangeretin and 3,5,6,7,8,3′,4′-heptamethoxyflavone jointly contributed to anticancer activity of PCR-C during storage. PCR-CF and the most important PMFs killed cancer cells (A549 cells) but had no cytotoxicity to normal lung fibroblast cells (MRC-5 cells). Overall, the high quality of long-term stored PCR-C might be due to the anticancer effects of tangeretin and 3,5,6,7,8,3′,4′-heptamethoxyflavone.

Marine derivatives prevent E6 protein of HPV: An in silico study for drug development

Cervical cancer (CC) is one of the most common cancers in women worldwide in which most cases are diagnosed with the Human Papilloma Virus (HPV). At the present time, there is neither a vaccine nor a drug to prevent or to effectively treat HPV infection. In the recent decades, compounds originated from marine organisms are well known for their novel chemical structures and wide range of biological activities. In the frame of our ongoing program to identify natural compounds endowed with anticancer bioactivities, this study conducted in silico assessment of 502 compounds originated from marine organisms against E6 protein of HPV for potential inhibition activity. The tertiary structure of targeted protein was constructed using SWISS-MODEL in which obtained Ramachandran plot proved the high quality of the protein model with 87.7% residues located in the most favored region and 11.6% residues allocated in the allowed region. All studied compounds were evaluated for drug-like and pharmacokinetic properties. AutoDock 4.2.6 and AutoDock Vina 1.2.0 were utilized to investigate the docking conformation of studied compounds towards E6 protein. High correlation coefficient between the dock score of AutoDock 4.2.6 and AutoDock Vina 1.2.0 was recorded with the value of R = 0.62. Docking outcomes in combination with ADMET studies identified compounds 153, 185 and 500 are the top “hits” for further drug development based on dock score ranking and docking conformation analysis, in particularly, compound 153 could be considered with caution due to its potent in causing mutation.

Anticancer bioactivity of zerumbone on pediatric rhabdomyosarcoma cells

PurposeNatural products are generally regarded as safe and have been shown to mediate anticancer activities against a variety of cell types. Zerumbone is a natural cyclic sesquiterpene derived from the rhizome of Zingiber zerumbet, which has attracted extensive attention in the recent decade for anticancer activities. The present study investigates the in vitro effect of zerumbone on rhabdomyosarcoma cells.MethodsTwo rhabdomyosarcoma cell lines (RD and RH30) were used as the model system. The growth inhibition of zerumbone was measured by MTT-assay, apoptosis via flow cytometry, gene expression by real-time PCR, the migration by transwell assay, and intracellular signaling by Western blotting.ResultsZerumbone shows anticancer effects on RD and RH30 cells in a dose-dependent manner via cell growth inhibition and induction of apoptosis. Exposure of RD and RH30 cells on zerumbone also resulted in a decrease of migration and downregulation of the hedgehog pathway.ConclusionsTaken together, our study provided the first evidence that zerumbone imparted strong inhibitory and apoptotic effects on pediatric rhabdomyosarcoma cell lines and merit further investigation as a promising candidate for the anticancer therapy.

Preclinical Pharmacokinetics, Biodistribution, and Acute Toxicity Evaluation of Caerin 1.9 Peptide in Sprague Dawley Rats.

Caerin 1.9 is a natural peptide derived from the skin secretions of the Australian tree frog (Litoria) with broad-spectrum antimicrobial and anticancer bioactivity. It improves the efficacy of a therapeutic vaccine and immune checkpoint inhibitor therapy when injected intratumorally and inhibits TC-1 tumor growth when applied topically through intact skin in a TC-1 murine tumor model. This paper investigated the pharmaceutical kinetic profile, the tissue distribution, and the acute safety investigation of Caerin 1.9 peptide in Sprague Dawley (SD) rats. The results showed that subcutaneous injection of Caerin 1.9 at 100 mg/kg is safe and does not cause mortality or organ malfunction in the recipient rats. For the consecutive injection of F3 at 10 mg/kg, the peak concentration (Cmax) of F3 displayed at 1 hr after injection in male rats was 591 ng/mL, the average drug retention time was 0.807 hr, T1/2 was 4.58 hr, and AUC0-last was 1890 h × ng/mL. In female rats, Cmax was 256 ng/mL, with an average drug retention time of 2.96 hr, T1/2 of 1.33 hr, and AUC0-last of 740 h × ng/mL. The results showed that the concentration of Caerin 1.9 in the peripheral blood peaked at 1 hour. As injected concentration increased, T1/2 extended, and Cmax, AUC0-last, and volume of distribution at a steady state all increased. After 14 days of repeated subcutaneous injection at 10.0 mg/kg, no accumulation of Caerin 1.9 in plasma was observed. The results of tissue distribution showed that the Caerin 1.9 is below the LC-MS/MS detection threshold at a minimum concentration of 40 ng/g. In conclusion, Caerin 1.9 is well tolerated in rats and could be used with current immunotherapies for better management of solid tumors and genital warts.

Marine Cyanobacteria as Sources of Lead Anticancer Compounds: A Review of Families of Metabolites with Cytotoxic, Antiproliferative, and Antineoplastic Effects.

The marine environment is highly diverse, each living creature fighting to establish and proliferate. Among marine organisms, cyanobacteria are astounding secondary metabolite producers representing a wonderful source of biologically active molecules aimed to communicate, defend from predators, or compete. Studies on these molecules’ origins and activities have been systematic, although much is still to be discovered. Their broad chemical diversity results from integrating peptide and polyketide synthetases and synthases, along with cascades of biosynthetic transformations resulting in new chemical structures. Cyanobacteria are glycolipid, macrolide, peptide, and polyketide producers, and to date, hundreds of these molecules have been isolated and tested. Many of these compounds have demonstrated important bioactivities such as cytotoxicity, antineoplastic, and antiproliferative activity with potential pharmacological uses. Some are currently under clinical investigation. Additionally, conventional chemotherapeutic treatments include drugs with a well-known range of side effects, making anticancer drug research from new sources, such as marine cyanobacteria, necessary. This review is focused on the anticancer bioactivities of metabolites produced by marine cyanobacteria, emphasizing the identification of each variant of the metabolite family, their chemical structures, and the mechanisms of action underlying their biological and pharmacological activities.

Bioactive peptides-derived from marine by-products: development, health benefits and potential application in biomedicine

Increased fisheries products have raised by-products that are discarded due to low economic value. In addition, marine by-products are still rich in protein and nutritional value that have biological activities and give benefits to human health. Meanwhile, there is raised pressure for sustainability practices in marine industries to reduce waste and minimize the detrimental effect on the environment. Thus, valorization by-products through bioactive peptide mining are crucial. This review focus on various ways to obtain bioactive peptides from marine by-products through protein hydrolysis, for instance chemical hydrolysis (acid and based), biochemical hydrolysis (autolysis and enzymatic hydrolysis), microbial fermentation, and subcritical water hydrolysis. Nevertheless, these processes have benefits and drawbacks which need to be considered. This review also addresses various biological activities that are favorable in pharmaceutical industries, including antioxidant, antihypertensive, anticancer, anti-obesity, and other beneficial bioactivities. In addition, some potential marine resources of Indonesia for the marine biopeptide from their by-product or undesired marine commodities would be addressed as well.

Microfluidic-assisted synthesis and modeling of stimuli-responsive monodispersed chitosan microgels for drug delivery applications

Droplet microfluidic has been established to synthesize and functionalize micro/nanoparticles for drug delivery and screening, biosensing, cell/tissue engineering, lab-on-a-chip, and organ-on-a-chip have attracted much attention in chemical and biomedical engineering. Chitosan (CS) has been suggested for different biomedical applications due to its unique characteristics, such as antibacterial bioactivities, immune-enhancing influences, and anticancer bioactivities. The simulation results exhibited an alternative for attaining visions in this complex method. In this regard, the role of the flow rate ratio on the CS droplet features, including the generation rate and droplet size, were thoroughly described. Based on the results, an appropriate protocol was advanced for controlling the CS droplet properties for comparing their properties, such as the rate and size of the CS droplets in the microchip. Also, a level set (LS) laminar two-phase flow system was utilized to study the CS droplet-breaking process in the Flow Focused-based microchip. The outcomes demonstrated that different sizes and geometries of CS droplets could be established via varying the several parameters that validated addressing the different challenges for several purposes like drug delivery (the droplets with smaller sizes), tissue engineering, and cell encapsulation (the droplets with larger sizes), lab-on-a-chip, organ-on-a-chip, biosensing and bioimaging (the droplets with different sizes). An experimental study was added to confirm the simulation results. A drug delivery application was established to verify the claim.

Dihydroquercetin Attenuates Silica-Induced Pulmonary Fibrosis by Inhibiting Ferroptosis Signaling Pathway.

Silicosis is a fatal occupational lung disease which currently has no effective treatment. Dihydroquercetin (DHQ) is a flavonoid compound known for its anti-inflammatory, anti-oxidant and anti-cancer bioactivity. However, whether DHQ protects against silica-induced lung fibrosis remains unknown. Therefore, we aimed to investigate the effect of DHQ on silica-induced lung fibrosis and the underlying molecular mechanism in vivo and in vitro. Our results demonstrated that DHQ treatment markedly attenuated SiO2-induced inflammation and fibrosis degree of lung tissues in the C57BL/6 mice. Additionally, experiments in vitro also confirmed that conditioned medium from DHQ-treated human bronchial epithelial (HBE) cells significantly decreased expression of fibrosis markers of human fetal lung fibroblast cells (MRC-5), such as α-SMA, collagen1 and fibronectin. Interestingly, HBE cells treated by DHQ showed few morphological features of ferroptosis compared with SiO2-treated cells. Furthermore, DHQ treatment remarkably inhibited ferroptosis in activated HBE cells by decreasing the accumulation of iron and lipid peroxidation products, and increasing levels of glutathione (GSH) and glutathione peroxidase 4 (GPX4), whereas stimulation of ferroptosis by specific inducer erastin deeply impaired anti-fibrosis effect of DHQ in vitro. More importantly, our results showed that DHQ also evidently suppressed ferritinophagy by down-regulation of microtubule-associated protein 1A/1B-light chain 3 (LC3), and up-regulation of ferritin heavy chain 1 (FTH1), nuclear receptor co-activator 4 (NCOA4) in activated HBE cells. Nevertheless, activation of ferritinophagy by specific inducer rapamycin (Rapa) evidently blocked DHQ-inhibited HBE cells ferritinophagy and anti-fibrosis effect of DHQ. Overall, our research revealed that inhibition of ferritinophagy-mediated HBE cells ferroptosis was responsible for DHQ to ameliorate SiO2-induced lung fibrosis, which provided a preliminary theoretical basis for the clinical application of DHQ in the treatment of silicosis.

A pH-Dependent rhodamine fluorophore with antiproliferative activity of bladder cancer in Vitro/Vivo and apoptosis mechanism

Herein, 26 rhodamine fluorophores were synthesized from readily available Rh-6G and relative amines at room temperature with good selectivity, functional groups compatibility and high yields. We found that one of them 3f showed pH-dependent anticancer bioactivity, with cell viability of 68.4% under pH 6.5 and 83.2% under pH 7.5, LDH fold change of 42.8% under pH 6.5 and 26.4% under pH 7.5 in 22.35 μM in human bladder cancer cell line EJ. Besides, 3f showed anticancer bioactivity in vivo towards human bladder cancer, by triggering apoptosis through mitochondrial pathway.

Microalgae Bioactive Carbohydrates as a Novel Sustainable and Eco-Friendly Source of Prebiotics: Emerging Health Functionality and Recent Technologies for Extraction and Detection.

There is a global interest in the novel consumption, nutritional trends, and the market of new prebiotic sources and their potential functional impacts. Commercially available nutritional supplements based on microalgae that are approved to be edible by FDA, like Arthrospira platensis (Cyanobacteria) and Chlorella vulgaris (Chlorophyta) become widely attractive. Microalgae are rich in carbohydrates, proteins, and polyunsaturated fatty acids that have high bioactivity. Recently, scientists are studying the microalgae polysaccharides (PS) or their derivatives (as dietary fibers) for their potential action as a novel prebiotic source for functional foods. Besides, the microalgae prebiotic polysaccharides are used for medication due to their antioxidant, anticancer, and antihypertensive bioactivities. This review provides an overview of microalgae prebiotics and other macromolecules’ health benefits. The phytochemistry of various species as alternative future sources of novel polysaccharides were mentioned. The application as well as the production constraints and multidisciplinary approaches for evaluating microalgae phytochemistry were discussed. Additionally, the association between this potential of combining techniques like spectroscopic, chromatographic, and electrochemical analyses for microalgae sensation and analysis novelty compared to the chemical methods was emphasized.

An Insight into Anticancer Bioactives from Punica granatum (Pomegranate).

Cancer is one of the major reasons for mortality across the globe. Many side-effects are associated with the formulations available in the market, affecting the quality of life of the patients. This has caused the researchers to find an alternative source of medications, such as herbal medicine, showing a promising effect in anticancer treatment; one such source is Pomegranate, which belongs to the family Punicaceae. Punica granatum contains many polyphenols that have antioxidant, antidiabetic, and therapeutic effects in the treatment and management of metabolic and cardiovascular diseases, as well as a favourable effect on anticancer therapy. Polyphenols like punicalin, punicalagin, and ellagic acid are a few of the many compounds responsible for the anticancer activity of pomegranate. Many preparations of pomegranate, such as Pomegranate Juice (PJ), Pomegranate Seed Oil (PSO), Pomegranate peel extract (PoPx), etc. are used in various clinical studies. These polyphenols show anticancer activity by either arresting the cell cycle in the G2/M phase, inducing apoptosis or damaging the DNA of tumor cells. This review explicitly discusses the role and mechanism of bioactives obtained from the pomegranate in the treatment and management of cancer. The chemical structure, properties, and role of pomegranate in the treatment of breast, lung, thyroid, colon, and prostate cancer have been focused on in detail. This review also discusses various targeted drug delivery approaches for tumour treatment as well as patented preparation of pomegranate compounds along with the ongoing clinical trials.

Inducing apoptosis in human hepatocellular carcinoma cell lines via Nrf2/HO-1 signalling pathway of blueberry and blackcurrant powder manipulated oat bran paste extracts

In this study, oat bran was enriched with blackcurrant and blueberry powder to form the oat bran paste separately. The paste extracts were used to investigate their effects on anticancer bioactivity towards hepatocellular carcinoma cells. Results showed 25% of berry powder-enriched paste extracts significantly inhibited the growth and invasion of hepatocellular carcinoma cells. Blackcurrant-enriched paste extract exhibited a better anticancer property than that of blueberry-enriched paste extract. Mechanistic studies suggested that the berry powder-enriched paste extracts induced cell apoptosis, being initiated through cell cycle arrest and regulating apoptotic-related protein expressions. Reactive oxygen species levels of hepatocellular carcinoma cells increased via regulating nuclear factor-like 2 (Nrf2)/heme oxygenase 1 (HO1) signalling pathway. These findings confirmed the therapeutic potential of the blueberry powder- and blackcurrant powder-enriched oat bran paste for patients with liver cancer.

Paeoniflorigenone regulates apoptosis, autophagy, and necroptosis to induce anti-cancer bioactivities in human head and neck squamous cell carcinomas

Ethnopharmacological relevancePaonia suffruticosa Andr. belonging to the family Paeoniaceae and has been used as a medicinal plant in Asian countries including China, Korea, and Japan. The roots of P. suffruticosa has been used in traditional medicine in various diseases including cancer and cardiovascular, female genital, and inflammatory diseases. Aim of the studyHead and neck squamous cell carcinomas (HNSCCs) pathologically account for 90% of all head and neck cancers. However, effective targeted therapies for HNSCCs are insufficient and the prognosis is very poor, especially in patients with metastatic HNSCCs. To overcome the current limitations of available therapies for HNSCCs, pathological approaches using natural compounds are attracting attention. Our study aimed to demonstrate the anti-cancer effects of paeoniflorigenone (Paeo, 98.9% purity) isolated from the root bark of P. suffruticosa. Materials and methodsOur scientific methodology was performed as follows: cytotoxicity, morphological changes, and apototic DNA fragmentation were analyzed using MTT, light microscopy, and TUNEL assays. Protein expression, apoptosis, necroptosis, and autophagy were analyzed using Western blot and immunofluorescence assays. Cell migration and invasion were analyzed using wound healing and Boyden chamber assays. ResultsWe demonstrated that Paeo significantly reduced cell proliferation and cell division, leading to caspase-dependent apoptotic cell death in human YD-10B HNSCC cells. This result was associated with PI3K/AKT/mTOR/p70S6K signaling in these cells. In addition, we investigated other programmed cell death mechanisms associated with apoptosis and found that Paeo inhibited necroptosis via dephosphorylation of key necroptotic proteins (RIP and MLKL), whereas Paeo induced autophagy via increased LC3I/II expression and autophagosome formation in human YD-10B HNSCC cells. The anti-metastatic effects of Paeo significantly suppressed cell migration and invasion in human YD-10B HNSCC cells. ConclusionOverall, our results demonstrated that the bioactive compound, Paeo, exhibited anti-cancer bioactivities in human YD-10B HNSCC cells, suggesting that Paeo may be an attractive pathological approach for patients with human HNSCCs.