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Background: Polyphenols found abundantly in plants exhibit various anti-carcinogenic effects on tumor cells, including angiogenesis, metastasis, anti-proliferating agents, inflammation, and apoptosis. In recent years, many novel polyphenolic compounds with anticancer activity have been identified worldwide, and few of them are promising anticancer drugs to cure or inhibit cancer growth by interfering with cancer initiation, promotion, and progression. Objective: This mini-review aims to provide a comprehensive survey of the information about poly-phenolic anticancer drugs disclosed in worldwide patents and discuss their possibility of developing as drugs used as anticancer drugs in clinical settings. Methods: In the present mini-review, we have revealed the anticancer properties of polyphenols pre-sented according to their mechanisms of action. PubMed, Google Patents, and SciDirect databases were used to compile the present study. Results: In the last five years, various anticancer polyphenols were revealed in worldwide patents in the last decades, and their mode of action pointed out cytoskeletal damage, arresting cell cycle, in-hibiting kinase, and tumor suppressor protein expression. Conclusion: Many newly found polyphenols display a promising anticancer potential both in vitro and in vivo, and a few anticancer polyphenols act to inhibit the growth of various human cancer cells. Also, we have given an overview of patents filed in the last five years related to the anticancer poten-tials of polyphenols.

Over the past several decades, xenobiotic chemicals have badly affected the environment including human health, ecosystem and environment. Animal-sourced biopolymers have been employed for the removal of heavy metals and organic dyes from the contaminated soil and waste waters. Animal-sourced biopolymers are biocompatible, cost-effective, eco-friendly, and sustainable in nature which make them a favorable choice for the mitigation of xenobiotic and hazardous compounds. Chitin/chitosan, collagen, gelatin, keratin, and silk fibroin-based biopolymers are the most commonly used biopolymers. This chapter reviews the current challenge faced in applying these animal-based biopolymers in eliminating/neutralizing various recalcitrant chemicals and dyes from the environment. This chapter ends with the discussion on the recent advancements and future development in the employability of these biopolymers in such environmental applications.

Aim: The current study explores the toxic consequences of ethanol on human lung carcinoma cell, A549 in serum-deprived condition. Methodology: Human lung carcinoma cells, A549, were cultured in complete and serum-deprived medium for 6 hr. Subsequently, they were exposed to 50 mM and 100 mM concentrations of ethanol. Cytotoxicity studies linked with cell viability, oxidative stress, cell cycle arrest and micronuclei formation were performed using various toxicological parameters, namely MTT assay, DCFDA based ROS generation, cell cycle analysis and micronuclei formation assay. The cytotoxicity of ethanol in complete and serum deprived medium were compared at similar doses and time duration. Results: The metabolic viability assay demonstrated that 50 mM and 100 mM concentration of ethanol did not induce significant levels of cytotoxic alteration in A549 lung carcinoma cells in complete medium. However, in serum-deprived conditions, 50 mM and 100 mM ethanol concentration significantly altered cell viability. Further, exposure of 50 mM and 100 mM concentration of ethanol enhanced reactive oxygen species levels in A549 cells more significantly in serum-deprived conditions than in complete medium. In addition to cytotoxicity and oxidative stress, 50 mM and 100 mM ethanol also arrested the cells at G0 phase more significantly in serum deprived conditions compared to complete medium. Interpretation: Both 50 mM and 100 mM ethanol concentration enhanced the cell cytotoxicity and reactive oxygen species, cell cycle arrest and micronuclei formation more severely in serum-deprived medium than in complete medium (containing 10% FBS) under similar treatment conditions.

Many diseases, such as rheumatoid arthritis, neurodegenerative disease, lupus, autoimmune disease, and cancer, are described by chronic inflammation following tissue damage. Anti-inflammatory drugs like non-steroidal anti-inflammatory drugs and other steroids cause many side effects and generally need careful consideration and monitoring during usage. In recent years, a significant interest in plant-derived approaches has been warranted. The bioactive glycoside syringin might be one of the effective immunomodulatory agents. However, its immunomodulatory potential needs to be better known. In this study, we evaluated the immunomodulatory potential of syringin using network pharmacology, molecular docking, and molecular dynamics simulation-based approaches. First, we applied the GeneCards and OMIM databases to acquire the immunomodulatory agents. Then, the STRING database was utilized to get the hub genes. Interaction analysis and molecular docking described strong binding of the active site of immunomodulatory proteins with the bioactive syringin. Molecular dynamics simulations (200 ns) showed a very stable interaction of syringin with the immunomodulatory protein. Further, the optimized structure and molecular electrostatic potential of the syringin were calculated by a density-functional theory utilizing basis levels of B3LYP/6-31. Syringin investigated in this study holds the required drug-likeness characteristics and follows Lipinski’s rule of five. However, quantum-chemical estimations show the syringin has potent reactivity, demonstrating a lower energy gap. Furthermore, the gap between ELUMO and EHOMO was low, suggesting the excellent affinity of syringin towards the immunomodulatory proteins. The present study shows that syringin might be an effective immunomodulatory agent and can be further explored using different experimental methods. Communicated by Ramaswamy H. Sarma

Aim of the study Glioblastoma multiforme (GBM) is the most severe forms of brain cancer, eventually becoming the leading cause of brain cancer-related death worldwide. Owing to the bleak surgical interventions and resistance to the different treatment regime, GBM is a parlous disease demanding newer therapeutical perspective for its treatment. Toll-like receptors (TLRs) are well-known members of pathogen recognition receptors (PRRs) and have been extensively explored for their therapeutic and prophylactic potential in an array of disease including cancer. Recent trends in drug delivery research has shown shift towards delivering short DNA sequences (CpG DNA) to endosomal TLR9 within immune cells (macrophages, dendritic cells, etc.) for the activation of desired inflammatory response using non-agonistic β-glucan particles; a well-known ligand for Dectin-1 receptors. Our study is therefore focused to explore the role of nano-encapsulated CpG ODN as critical players in polarizing M2 scavenging to much desired pro-inflammatory type. Materials and methods The nanoparticles entrapping CpG ODN 1826 were prepared by using a fungal polymer Schizophyllan (SPG). The constructed nanoparticles were characterized and assessed for their efficacy on rat glioblastoma cells (C6). Results The constructed Schizophyllan (SPG) nanoparticles entrapping CpG ODN 1826 (95.3%) were of 25.49 nm in diameter and thus capable of crossing blood-brain barrier. The rat glioblastoma (C6) cells evaluated for intracellular oxidative burst and cytokine levels pre- and post-incubation with nanoparticles exhibited marked elevation in the expression of intracellular ROS and IFN-γ as well as IL-1β post treatment. Conclusion The findings indicate towards potentiality of repolarizing the M2 macrophages to much desired M1 phase by inducing higgh levels of oxidative burst and inflammatory cytokines. Consequently, the apoptosis was induced in glioblastoma cells establishing the suitablity of CpG ODN carrying nanoformulations as emerging therapeutic intervention for GBM.

Background: Several studies have revealed that abnormal activation of Notch signaling is closely related with the development and progression of prostate cancer. Although there are numerous therapeutic strategies, a more effective modality with least side effects is urgently required for the treatment of prostate cancer. Carvacrol is a monoterpenoid phenol and majorly present in the essential oils of Lamiaceae family plants. Many previous reports have shown various biological activities of carvacrol like antioxidant, antiinflammatory and anticancer properties. Recently, we have shown potent anticancer property of carvacrol against prostate cancer cell line DU145. In the current study, we report the chemopreventive and therapeutic potential of carvacrol against another prostate cancer cell line PC-3 with its detailed mechanism of action. Methods: To determine the effect of the carvacrol on prostate cancer cells, the cell viability was estimated by MTT assay and cell death was estimated by LDH release assay. The apoptotic assay was performed by DAPI staining and FITC-Annexin V assay. Reactive Oxygen Species (ROS) was estimated by DCFDA method. Cell cycle analysis was performed by flow cytometry. Gene expression analysis was performed by quantitative real time PCR. Results: Our results suggested that the carvacrol treatment significantly reduced the cell viability of PC-3 cells in a dose- and time-dependent manner. The antiproliferative action of carvacrol was correlated with apoptosis which was confirmed by nuclear condensation, FITC-Annexin V assay, modulation in expression of Bax, Bcl-2 and caspase activation. The mechanistic insight into carvacrol-induced apoptosis leads to finding of elevated level of Reactive Oxygen Species (ROS) and mitochondrial membrane potential disruption. Cell cycle analysis revealed that carvacrol prevented cell cycle in G0/G1 that was associated with decline in expression of cyclin D1 and Cyclin-Dependent Kinase 4 (CDK4) and augmented expression of CDK inhibitor p21. Having been said the role of hyperactivation of Notch signaling in prostate cancer, we also deciphered that carvacrol could inhibit Notch signaling in PC-3 cells via downregulation of Notch-1, and Jagged-1. Conclusion: Thus, our previous and current findings have established the strong potential of carvacrol as a chemopreventive agent against androgen-independent human prostate cancer cells.

Naturally occurring phytochemicals or plant derivatives are now being explored extensively for their health's benefits and medicinal uses. The therapeutic effect of phytochemicals has been reported in several pathophysiological settings such as inflammatory disorders, metabolic disorders, liver dysfunction, neurodegenerative disorders, and nephropathies. However, the most warranted therapeutic effects of phytochemicals were mapped to their anticancerous and chemopreventive action. Moreover, combining phytochemicals with standard chemotherapy has shown promising results in cancer therapy with minimal side effects and better efficacy. Many phytochemicals, like curcumin, resveratrol, and epigallocatechin-3-gallate, have been extensively investigated for their chemopreventive as well as chemotherapeutic effects. However, poor bioavailability, low solubility, hydrophobicity, and obscure target specificity restrict their therapeutic applications in the clinic. There has been a continually increasing interest to formulate nanoformulations of phytochemicals by using various nanocarriers, such as liposomes, micelles, nanoemulsions, and nanoparticles, to improve their bioavailability and target specificity, thereby maximizing the therapeutic potential. In the present review, we have summarized chemopreventive as well as chemotherapeutic action of some common phytochemicals and their major limitations in clinical application. Also, we have given an overview of strategies that can improve the efficacy of phytochemicals for their chemotherapeutic value in clinical settings.

Exposure to environmental endocrine disrupting chemicals (EDCs) is highly suspected in prostate carcinogenesis. Though, estrogenicity is the most studied behavior of EDCs, the androgenic potential of most of the EDCs remains elusive. This study investigates the androgen mimicking potential of some common EDCs and their effect in androgen-dependent prostate cancer (LNCaP) cells. Based on the In silico interaction study, all the 8 EDCs tested were found to interact with androgen receptor with different binding energies. Further, the luciferase reporter activity confirmed the androgen mimicking potential of 4 EDCs namely benzo[a]pyrene, dichlorvos, genistein and β-endosulfan. Whereas, aldrin, malathion, tebuconazole and DDT were reported as antiandrogenic in luciferase reporter activity assay. Next, the nanomolar concentration of androgen mimicking EDCs (benzo[a]pyrene, dichlorvos, genistein and β-endosulfan) significantly enhanced the expression of AR protein and subsequent nuclear translocation in LNCaP cells. Our In silico studies further demonstrated that androgenic EDCs also bind with epigenetic regulatory enzymes namely DNMT1 and HDAC1. Moreover, exposure to these EDCs enhanced the protein expression of DNMT1 and HDAC1 in LNCaP cells. These observations suggest that EDCs may regulate proliferation in androgen sensitive LNCaP cells by acting as androgen mimicking ligands for AR signaling as well as by regulating epigenetic machinery. Both androgenic potential and epigenetic modulatory effects of EDCs may underlie the development and growth of prostate cancer.

Platinum containing drugs are widely used to treat advanced lung carcinomas. However, their clinical success is still limited due to severe side effects, and drug resistance. Alternative approaches are warranted to augment efficacy of platinum based chemotherapeutic drugs with minimal side effects. Intricatinol (INT), a homoisoflavonoid, has been shown to possess anti-tubercular, antioxidant, hypoglycaemic, and hypolipidemic activity. However, its anticancer activity largely remains unknown. In the present study, we have evaluated anticancer potential of INT alone or in combination with cisplatin (CIS) in non-small cell lung carcinoma (A549) cells. Treatment with INT alone reduced the viability of A549 cells in a dose-dependent manner. Interestingly, the combination of low doses of INT and CIS exerted a synergistic effect and induced apoptosis as evident by DNA fragmentation and Annexin V positive cells. Enhanced Bax:Bcl-2 ratio, loss of Δψm, cytochrome c release, cleavage of caspase 3 and PARP1 strongly corroborated our findings. Further, increased expression of p53, p38 MAPK and their phosphorylated counterparts, loss of clonogenicity and reduced migration potential were also recorded with INT + CIS treatment. Most interestingly, INT could not induce any significant cell death in primary mouse embryonic fibroblasts (MEFs). Moreover, no additive or synergistic effect was noted with INT + CIS in MEFs under similar treatment conditions. In conclusion, INT has a selective anticancer potential and could synergize cytotoxicity of CIS. Therefore, the combination of INT and CIS may serve as an effective anticancer strategy for the treatment of non-small cell lung carcinoma.