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The role of genetic and epigenetic factors in tumor initiation and progression is well documented. Histone deacetylases (HDACs), histone methyl transferases (HMTs), and DNA methyl transferases. (DNMTs) are the main proteins that are involved in regulating the chromatin conformation. Among these, histone deacetylases (HDAC) deacetylate the histone and induce gene repression thereby leading to cancer. In contrast, histone acetyl transferases (HATs) that include GCN5, p300/CBP, PCAF, Tip 60 acetylate the histones. HDAC inhibitors are potent drug molecules that can induce acetylation of histones at lysine residues and induce open chromatin conformation at tumor suppressor gene loci and thus resulting in tumor suppression. The key processes regulated by HDAC inhibitors include cell-cycle arrest, chemo-sensitization, apoptosis induction, upregulation of tumor suppressors. Even though FDA approved drugs are confined mainly to haematological malignancies, the research on HDAC inhibitors in glioblastoma multiforme and triple negative breast cancer (TNBC) are providing positive results. Thus, several combinations of HDAC inhibitors along with DNA methyl transferase inhibitors and histone methyl transferase inhibitors are in clinical trials. This review focuses on how HDAC inhibitors regulate the expression of coding and non-coding genes with specific emphasis on their anti-cancer potential., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Pancreatic cancer is one of the most malignant cancers around the world. The co-occurrence of mutation in KRAS and p53 makes it highly aggressive, proliferative, metastatic, and resistant to apoptotic cell death. Therefore, there is a need to trigger an alternate mechanism of cancer cell death in apoptosis-resistant pancreatic cancer. Autophagic cell death could be an alternate viable option for treatment in such cases. Thus, the identification of small molecules as autophagy modulators with potent anticancer efficacy would be of great importance in pancreatic cancer. The present study investigates fluorinated thiazolidionol (FTZ) driven autophagy modulation, underlying mechanism, and regulation of critical sentinels of oncogenic signaling in pancreatic cancer cells. We identified that FTZ triggered autophagic cell death in pancreatic cancer cells, independent of apoptosis evidenced by an increase in cytoplasmic vacuoles formation, autophagy flux, LC3-II expression, and p62 degradation. Further, the crucial events of apoptosis i.e., Caspase-3 activation and PARP cleavage, were not observed, indicating the non-occurrence of apoptotic cell death. Moreover, FTZ was able to activate AMPK and suppress PI3k/Akt/mTOR as well as MEK/ERK, the key oncogenic signaling pathways in cancer cells. Furthermore, treatment with FTZ suppressed migration, invasion, and angiogenesis in pancreatic cancer cells. Studies in vivo revealed significant regression of tumors by FTZ in nude mice model. Overall, our study demonstrates that FTZ induces autophagic cell death in pancreatic cancer cells independent of apoptosis, which is accompanied by AMPK activation and suppression of critical sentinels of oncogenic signaling in pancreatic cancer cells., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Low molecular weight antimicrobial polypeptides were extracted and purified from the young fresh leaves of Azadirachta indica (neem). The total protein extracted was precipitated with 15% TCA-Acetone. The total purified proteins yielded from the two extraction methods were 122.33±2.21 and 115.09±1.88mg/g of the total fresh weight. The SDS-PAGE analysis identified the presence of eight low molecular weight polypeptide bands. The antimicrobial activity of the resolved bands was detected by Polyacrylamide gel-Agar overlay diffusion assay (PAG-ADA). Their broad-spectrum bactericidal activity was confirmed using the same technique and found three low molecular weight bands from 11 to 14kDa collectively exhibiting superior bactericidal activities against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermis, Enterococcus faecalis, Pseudomonas aeruginosa and fungicidal activity against Candida tropicalis. The FTIR spectrum of the protein bands depicted the presence of hydroxyl and carbonyl groups in the protein bands. These polypeptides were characterized by MALDI-TOF/TOF analysis. Further, the purified protein extract was found to be active against HELA, BT-549 and Neuro-2a cell lines with IC 50 value of 74.03±2.31, 64.82±1.64, 238.32±2.12 and 109.94±2.96, 59.61±0.75 for 24h and 48h, respectively. The results of present study indicate that these polypeptides exhibit broad spectrum antimicrobial and anticancer activity and can therefore be explored for their therapeutic potential., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Prohibitin (PHB) is overtly conserved evolutionarily and ubiquitously expressed protein with pleiotropic functions in diverse cellular compartments. However, regulation and function of these proteins in different cells, tissues and in various diseases is different as evidenced by expression of these proteins which is found to be reduced in heart diseases, kidney diseases, lung disease, Crohn's disease and ulcerative colitis but this protein is highly expressed in diverse cancers. The mechanism by which this protein acts at the molecular level in different subcellular localizations or in different cells or tissues in different conditions (diseases or normal) has remained poorly understood. There are several studies reported to understand and decipher PHB's role in diseases and/or cancers of ovary, lung, stomach, thyroid, liver, blood, prostrate, gastric, esophagus, glioma, breast, bladder etc. where PHB is shown to act through mechanisms by acting as oncogene, tumor suppressor, antioxidant, antiapoptotic, in angiogenesis, autophagy etc., Objective: This review specifically gives attention to the functional role and regulatory mechanism of PHB proteins in cardiovascular health and diseases and its associated implications. Various molecular pathways involved in PHB function and its regulation are analyzed., Conclusion: PHB is rapidly emerging as a critical target molecule for cardiovascular signaling. Progress in delineating CVD and mechanisms of PHB in diverse molecular pathways is essential for determining when and how PHB targeted therapy might be feasible. In this regard, new therapies targeting PHB may best be applied in the future together with molecular profiling of CVD for clinical stratification of disease diagnosis and prognosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Microtubules form crucial dynamic structural cellular components of the cell and are composed of the alpha beta tubulin heterodimers. Microtubules are involved in a wide variety of functions in the cell such as attribution to cell shape, motility, intracellular trafficking and mitotic spindle formation. Owing to these reasons, tubulin and microtubules have gained significant interest as important targets for cancer therapy. A review of the existing microtubule targeting drugs specifies that these agents can be categorised into two of the major categories: Microtubule stabilizing agents such as paclitaxel, docetaxel, epothilones, and discodermolide which bind to the tubulin polymer and stabilize the microtubules, microtubule destabilizing agents such as vinca alkaloids, colchicine and combretastatins which bind to tubulin dimers and cause destabilization. These agents ultimately alter the equilibrium between tubulin and microtubule resulting in disruption of mitotic spindle, thereby effecting a critical transition in the cell cycle, leading to cell death. Further, clinical studies of these agents are limited by toxicity effects and emergence of drug resistance. The hybrid drugs are a combination of two or more drugs wherein pharmacophores are incorporated into a single molecule to interact with multiple targets and enhance the cytotoxic action with minimal side effects. Such hybrid regimens can improve therapeutic efficacy and reduce drug toxicity. Therefore, studies on new hybrids with such biological properties form important part in chemistry. In this review, we present an overview of various recent hybrids of colchicines, combretastatin, phodophyllotoxin, etc generated by combination among themselves through linkers or with other pharmacophores and their properties like tubulin stabilization and tubulin destabilization. We also attempted to provide chemistry, toxicity, resistance, side effects of these molecular hybrids acting as microtubule targeting drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)