Structure based docking and biological evaluation towards exploring potential anti-cancerous and apoptotic activity of 6-Gingerol against human prostate carcinoma cells.

BACKGROUND: 6-Gingerol (6-G) is the primary active phytocomponent of ginger and has been shown to regulate multiple targets against cancer and its treatment. Androgen receptors (ARs) remain critical in the progression of prostate cancer (PCa). This study focuses on investigating 6-G as a promising anti-cancerous agent that inhibits AR activity significantly. METHODS: In this study, molecular docking simulation was done to investigate the binding affinity of 6-G and control drug Bicalutamide (BT) against oncogenic AR and tumor suppressor estrogen receptor ß (ERß). The crystal structure of AR and ERß was retrieved from Protein Data Bank (PDB) and docked with 3D Pubchem structures of 6-G using iGEMDOCK and AutoDock. Further in vitro study was done to evaluate the antioxidant, anti-cancerous, apoptotic, and wound healing potential of 6-G. RESULTS: The result displays that 6-G shows good binding affinity with AR and ERß. Condensation of the nucleus, change in mitochondrial membrane potential (MMP) and the ability to induce reactive oxygen species (ROS) were done in human PCa PC-3 cells. Results from the MTT assay demonstrated that 6-G and control drug BT showed significant (p < 0.01) dose and time dependent inhibition of human PCa PC-3 cells. 6-G increased the ROS generation intracellularly and decreased the MMP, and cell migration in treated PCa PC-3 cells. 6-G treated cells showed fragmented, condensed chromatin and nuclear apoptotic bodies. CONCLUSIONS: Thus, this study validates 6-G as a potential drug candidate against human PCa. However, further study of the anticancer potency of 6-G has to be done before its use for PCa treatment.

CRISPR-Cas9: A Potent Gene-editing Tool for the Treatment of Cancer.

The prokaryotic adaptive immune system has clustered regularly interspaced short palindromic repeat. CRISPR-associated protein (CRISPR-Cas) genome editing systems have been harnessed. A robust programmed technique for efficient and accurate genome editing and gene targeting has been developed. Engineered cell therapy, in vivo gene therapy, animal modeling, and cancer diagnosis and treatment are all possible applications of this ground-breaking approach. Multiple genetic and epigenetic changes in cancer cells induce malignant cell growth and provide chemoresistance. The capacity to repair or ablate such mutations has enormous potential in the fight against cancer. The CRISPR-Cas9 genome editing method has recently become popular in cancer treatment research due to its excellent efficiency and accuracy. The preceding study has shown therapeutic potential in expanding our anticancer treatments by using CRISPR-Cas9 to directly target cancer cell genomic DNA in cellular and animal cancer models. In addition, CRISPR-Cas9 can combat oncogenic infections and test anticancer medicines. It may design immune cells and oncolytic viruses for cancer immunotherapeutic applications. In this review, these preclinical CRISPRCas9- based cancer therapeutic techniques are summarised, along with the hurdles and advancements in converting therapeutic CRISPR-Cas9 into clinical use. It will increase their applicability in cancer research.

The Role of Phytochemicals in Cancer Prevention: A Review with Emphasis on Baicalein, Fisetin, and Biochanin A.

Cancer is a disease in which repeated rounds of mutations cause uncontrolled growth of cells, which prospers at the expense of their neighbor cells and then eventually leads to the destruction of the whole cellular community. Chemopreventive drugs either prevent DNA damage, which results in malignancy, or they stop or reverse the division of premalignant cells with DNA damage, which inhibits the growth of cancer. There is an obvious need for an alternate strategy given the ongoing rise in cancer incidence, the ineffectiveness of traditional chemotherapies to control cancer, and the excessive toxicity of chemotherapies. From antiquity to date, the saga of the usage of plants as medicine has been the mainstay among people worldwide. In recent years, extensive studies have been conducted on medicinal plants, spices, and nutraceuticals, as these have gained much popularity in reducing the risk of several cancer types in humans. Extensive studies on cell culture systems and animal models have demonstrated that various medicinal plants and nutraceuticals from various natural resources and their products, such as major polyphenolic constituents, flavones, flavonoids, antioxidants, etc, provide considerable protection against many cancer types. As shown in the literatures, the major aim of studies conducted is to develop preventive/therapeutic agents which can induce apoptosis in cancer cells without affecting normal cells. Projects are going on worldwide to find better ways to eradicate the disease. The study of phytomedicines has shed new light on this topic as research to date has proven that they have antiproliferative and apoptotic capabilities that will aid in the development of novel cancer prevention options. Dietary substances, such as Baicalein, Fisetin, and Biochanin A have shown that they have an inhibitory effect on cancer cells, suggesting that they may work as chemopreventive agents. This review discusses the chemopreventive and anticancer mechanisms of such reported natural compounds.

Elucidating molecular and cellular targets and the antiprostate cancer potentials of promising phytochemicals: a review.

Prostate cancer (PCa) has become the major health problem and the leading causes of cancer mortality among men. PCa often progresses from an early androgen-dependent form of cancer to a late (metastatic) androgen-independent cancer, for which no effective treatment options are available. Current therapies target testosterone depletion, androgen axis inhibition, androgen receptor (AR) downregulation and regulation PSA expression. These conventional treatment options, however, are intense and pose severe side effects. From the past few years, plant-derived compounds or phytochemicals have attracted much attention by the researchers worldwide for their promising approach in inhibiting the development and growth of cancer. This review emphasizes mechanistic role of promising phytochemicals on PCa. This review imparts to score anticancer efficacy of promising phyto-agents luteolin, fisetin, coumestrol and hesperidin with focus on the mechanistic action in management and treatment of PCa. These phytocompounds were also selected for their best binding affinity with the ARs on the basis of molecular docking studies.

In vitro and in silico growth inhibitory, anti-ovarian & anti-lung carcinoma effects of 1,5 diarylpenta-1,4-dien-3-one as synthetically modified curcumin analogue.

The synthesized 1,5 diarylpenta-1,4-dien-3-one derivatives (compounds 1-6) as synthetic curcumin analogues were tested for their potential anticancer activity against human ovarian and lung adenocarcinoma cells. The absorption, distribution, metabolism, excretion, and toxicity (ADMET/pharmacokinetic) parameters of all the compounds were predicted by admetSAR software. The pharmacokinetics, pharmacodynamics and bioactivity scores properties based on Lipinski rule and Ghose filter, calculated with the help of Molinspiration and ChemDraw. Molecular docking evaluation of all the compounds was also performed by using AutoDock Vina and iGEMDOCK against three most common human anticancer targets; epidermal growth factor receptor (EGFR), heat shock protein (Hsp 90-α), and vascular endothelial growth factor receptor-2 (VEGFR2). The obtained results were compared with the reference compound 7 and drugs 8-10 (7: GO-035; 8: Quinazolin; 9: Naquotinib and 10: Ribofuranuronamide). Finding indicates, all the compounds were potentially interacting with VEGFR2 through the average -9.1 binding energy (BE) with closer contact <5.0 Å deep in the active site of the ligand-receptor complex. All the compounds showed excellent oral bioavailability, bioactivity score, and none of the compounds are virtually found to be toxic. Compounds 1-6 were also successfully characterized by the physical properties as well as spectroscopic techniques (FT-IR and 1H-NMR). In vitro anti-proliferative activity was tested via MTT method against human ovarian carcinoma (PA-1) and human lung adenocarcinoma (A549) cells and further screened for apoptotic parameters such as nuclear fragmentation and ROS generation. Compound 4 exhibits good dose-dependent anti-proliferative activity (IC50 73 and 79.7 µM) against human ovarian carcinoma and human lung adenocarcinoma, respectively.Communicated by Ramaswamy H. Sarma.

Antiosteoarthritic effect of Punica granatum L. peel extract on collagenase induced osteoarthritis rat by modulation of COL-2, MMP-3, and COX-2 expression.

Osteoarthritis (OA) is a chronic degenerative and musculoskeletal disorder. The toxicity associated with nonsteroidal antiinflammatory drugs (NSAIDs) limits its use in the management of OA. To ameliorate these toxicities, natural antioxidants can be used as substitutes for the management of OA. Therefore, this study is aimed to investigate the prophylactic mechanisms of Punica granatum L. peel (PGP) in collagenase-induced OA rat compared with indomethacin. OA was induced in female Sprague Dawley rats by intraarticular injection of collagenase type-II and treated with PGP (250 and 500 mg/kg body wt) and a positive control (PC) indomethacin (3 mg/kg body wt). The results demonstrated that PGP reduced the collagenase induced OA as compared with indomethacin treated group through reducing blood ALP (P < .001) and significantly (P < .001) inhibited cartilage erosion as indicated in histological slides with retention of collagen and proteoglycan content. Quantitative real-time PCR analysis revealed the considerable (P < .05) upregulation in the expression of COL-2 gene and downregulation of MMP-3 and COX-2 genes in the PGP treated group. The high phenolic content (633 ± 1.16 mg/GAE) and flavonoid content (420.3 ± 2.14 mg/RE) contribute to the strong antioxidant activity with IC50 value (320 ± 2.2 µg/mL) of DPPH free radical scavenging activity. These results need further validation in clinical studies and thus, PGP could be developed as a preventive drug treatment for OA.

Induction of apoptosis by piperine in human cervical adenocarcinoma via ROS mediated mitochondrial pathway and caspase-3 activation.

Piperine (1-piperoylpeperdine), a nitrogenous pungent substance, is present in the fruits of black pepper (Piper nigrum Linn.) and long pepper (Piper longum Linn.). It possesses several pharmacological properties and has been extensively explored for its anti-cancerous activities. The mechanism underlying its anti-cancer potential in human cervical adenocarcinoma (HeLa) cells is not well interpreted. The anti-proliferative effect and the mode of action of piperine were investigated through some potent markers of apoptosis viz.reactive oxygen species (ROS) generation, cellular apoptosis and loss of mitochondrial membrane potential (MMP). DNA fragmentation, cell cycle kinetics, caspase-3 activity and cell migration assays were also conducted to observe the efficacy of piperine against HeLa cells. The results showed that piperine exposure induces apoptosis significantly in a dose-dependent manner and inhibits the growth of HeLa cells with an increase in ROS generation, nuclear condensation and delayed wound healing. In addition, piperine also encourages cell death by the loss of MMP, DNA fragmentation and the activation of caspase-3. Growth inhibition of HeLa cells was found to be associated with G2/M phase arrest and sub-G1 accumulation. The present study provides useful insight into the apoptotic potential of piperine and further in vivo and clinical studies will be needed for its validation and in the finding of more effective and least toxic regimens against cervical cancer.

Phytochemicals in the treatment of ovarian cancer.

Ovarian cancer ranks 5th among the most common gynecologic cancers and causes the highest mortality in females. Here, we discuss the role of a group of natural products that are being used in treatment and prevention of a host of cancers including ovarian cancer. Some plants and nutraceuticals and their polyphenolic constituents such as flavones, flavonoids, and antioxidants have shown cytotoxic effects on cancer cells both in vitro and in vivo. While phytochemicals do not harm normal cells, they have been found to be cytotoxic to cancer cells by virtue of inhibition of proliferation and/or induction of apoptosis, making them ideal in cancer therapeutics or as adjunct to conventional treatment regimens.