Journal
PLOS ONE
Volume 9, Issue 6, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0099743
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Funding
- University Grants Commission [UGC 2-8/2002]
- Department of Science and Technology [DST R/3393/06]
- Department of Biotechnology-DBT-RA
- Council of Scientific and Industrial Research [CSIR 09/015(0386)/2010 EMR-1]
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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 feedback loop in these cells to persuade p53-mediated HIF-1 alpha degradation and SMAR1-induced repression of Cox-2 expression that restrained HIF-1 alpha 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.
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