title: Capsaicin-induced activation of p53-SMAR1 auto-regulatory loop down-regulates VEGF in non-small cell lung cancer to restrain angiogenesis.
abstract: Lung cancer is the leading cause of cancer-related deaths worldwide. Despite decades of research, the treatment options for lung cancer patients remain inadequate, either to offer a cure or even a substantial survival advantage owing to its intrinsic resistance to chemotherapy. Our results propose the effectiveness of capsaicin in down-regulating VEGF expression in non-small cell lung carcinoma (NSCLC) cells in hypoxic environment. Capsaicin-treatment re-activated p53-SMAR1 positive feed-back loop in these cells to persuade p53-mediated HIF-1α degradation and SMAR1-induced repression of Cox-2 expression that restrained HIF-1α nuclear localization. Such signal-modulations consequently down regulated VEGF expression to thwart endothelial cell migration and network formation, pre-requisites of angiogenesis in tumor micro-environment. The above results advocate the candidature of capsaicin in exclusively targeting angiogenesis by down-regulating VEGF in tumor cells to achieve more efficient and cogent therapy of resistant NSCLC.
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India.
authors.forename: Samik
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India.
authors.forename: Arghya
authors.initials: A
authors.lastname: Adhikary
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India.
authors.forename: Minakshi
authors.initials: M
authors.lastname: Mazumdar
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India.
authors.forename: Shravanti
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India.
authors.forename: Pushpak
authors.initials: P
authors.lastname: Bhattacharjee
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India.
authors.forename: Deblina
authors.initials: D
authors.lastname: Guha
authors.affiliation: Department of Biotechnology, Viswa-Bharati, Santiniketan, West Bengal, India.
authors.forename: Tathagata
authors.initials: T
authors.lastname: Choudhuri
authors.affiliation: National Center for Cell Science, Pune University, Pune, Maharashtra, India.
authors.forename: Samit
authors.initials: S
authors.lastname: Chattopadhyay
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India.
authors.forename: Gaurisankar
authors.initials: G
authors.lastname: Sa
authors.affiliation: Department of Microbiology, Lady Brabourne College, Kolkata, West Bengal, India.
authors.forename: Aparna
authors.initials: A
authors.lastname: Sen
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India.
authors.forename: Tanya
authors.initials: T
authors.lastname: Das
mesh_terms: D015153:Blotting, Western; D002211:Capsaicin / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D061986:MCF-7 Cells; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D002211:Capsaicin