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Aim: This study aims to investigate the mode of action of a novel sirtuin inhibitor (BZD9L1) and its associated molecular pathways in colorectal cancer (CRC) cells., Materials & Methods: BZD9L1 was tested against metastatic CRC cell lines to evaluate cytotoxicity, cell cycle and apoptosis, senescence, apoptosis related genes and protein expressions, as well as effect against major cancer signaling pathways., Results & Conclusion: BZD9L1 reduced the viability, cell migration and colony forming ability of both HCT 116 and HT-29 metastatic CRC cell lines through apoptosis. BZD9L1 regulated major cancer pathways differently in CRC with different mutation profiles. BZD9L1 exhibited anticancer activities as a cytotoxic drug in CRC and as a promising therapeutic strategy in CRC treatment.

Deregulated angiogenesis has been identified as a key contributor in a number of pathological conditions including cancer. It is a complex process, which involves highly regulated interaction of multiple signalling molecules. The pro-angiogenic signalling molecule, vascular endothelial growth factor (VEGF) and its cognate receptor 2 (VEGFR-2), which is often highly expressed in majority of human cancers, plays a central role in tumour angiogenesis. Owing to the importance of tumour vasculature in carcinogenesis, tumour blood vessels have emerged as an excellent therapeutic target. The anti-angiogenic therapies have been shown to arrest growth of solid tumours through multiple mechanisms, halting the expansion of tumour vasculature and transient normalization of tumour vasculature which help in the improvement of blood flow resulting in more uniform delivery of cytotoxic agents to the core of tumour mass. This also helps in reduction of hypoxia and interstitial pressure leading to reduced chemotherapy resistance and more uniform delivery of cytotoxic agents at the targeted site. Thus, complimentary combination of different agents that target multiple molecules in the angiogenic cascade may optimize inhibition of angiogenesis and improve clinical benefit in the cancer patients. This review provides an update on the current trend in exploitation of angiogenesis pathways as a strategy in the treatment of cancer., Competing Interests: The authors declare no conflict of interest.

Considering the great potential of natural products as anticancer agents, the present study was designed to explore the molecular mechanisms responsible for anticancer activities of Mesua ferrea stem bark extract against human colorectal carcinoma. Based on MTT assay results, bioactive sub-fraction (SF-3) was selected for further studies using HCT 116 cells. Repeated column chromatography resulted in isolation of less active α-amyrin from SF-3, which was identified and characterized by GC-MS and HPLC methods. α-amyrin and betulinic acid contents of SF-3 were measured by HPLC methods. Fluorescent assays revealed characteristic apoptotic features, including cell shrinkage, nuclear condensation, and marked decrease in mitochondrial membrane potential in SF-3 treated cells. In addition, increased levels of caspases-9 and -3/7 levels were also observed in SF-3 treated cells. SF-3 showed promising antimetastatic properties in multiple in vitro assays. Multi-pathway analysis revealed significant down-regulation of WNT, HIF-1α, and EGFR with simultaneous up-regulation of p53, Myc/Max, and TGF-β signalling pathways in SF-3 treated cells. In addition, promising growth inhibitory effects were observed in SF-3 treated HCT 116 tumour spheroids, which give a hint about in vivo antitumor efficacy of SF-3 phytoconstituents. In conclusion, these results demonstrated that anticancer effects of SF-3 towards colon cancer are through modulation of multiple molecular pathways., (Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

The current mechanistic study was conducted to explore the effects of increased lipophilicity of binuclear silver(I)-NHC complexes on cytotoxicity. Two new silver(I)-N-Heterocyclic Carbene (NHC) complexes (3 and 4), having lypophilic terminal alkyl chains (Octyl and Decyl), were derived from meta-xylyl linked bis-benzimidazolium salts (1 and 2). Each of the synthesized compounds was characterized by microanalysis and spectroscopic techniques. The complexes were tested for their cytotoxicity against a panel of human cancer c as well normal cell lines using MTT assay. Based on MTT assay results, complex 4 was found to be selectively toxic towards human colorectal carcinoma cell line (HCT 116). Complex 4 was further studied in detail to explore the mechanism of cell death and findings of the study revealed that complex 4 has promising pro-apoptotic and anti-metastatic activities against HCT 116 cells. Furthermore, it showed pronounced cytostatic effects in HCT 116 multicellular spheroid model. Hence, binuclear silver(I)-NHC complexes with longer terminal aliphatic chains have worth to be further studied against human colon cancer for the purpose of drug development., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)