Suppression of microphthalmia-associated transcription factor, but not NF-kappa B sensitizes melanoma specific cell death.
Mutation in B-Raf leads to gain of function in melanoma and causes aggressive behavior for proliferation. Most of the therapeutics are ineffective in this scenario. However, regulation of this aggressive behavior by targeting the key molecules would be viable strategy to develop novel and effective therapeutics. In this report we provide evidences that the resveratrol is potent to regulate melanoma cell growth than other inducers of apoptosis. Resveratrol inhibits pronounced cell proliferation in melanoma than other tumor cell types. Cell cycle analysis using flow cytometry shows that the treatment with resveratrol results in S phase arrest. Resveratrol inhibits microphthalmia-associated transcription factor (MITF) and its dependent genes without interfering the MITF DNA binding in vitro. Resveratrol-mediated cell death is protected in MITF overexpressed cells and it is aggravated in MITF knocked down cells. These suggest the resveratrol-mediated decrease in MITF is the possible cause of melanoma cell death. Though resveratrol-mediated downregulation of NF-κB is responsible for cell apoptosis, but the downregulation of MITF is the main reason for melanoma-specific cell death. Thus, resveratrol can be effective chemotherapeutic agent against rapid proliferative melanoma cells.
Laboratory of Immunology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, Telangana, 500 001, India.|Graduate studies, Manipal University, Manipal, Karnataka, 576104, India.
Raveendra B
RB
Mokhamatam
Laboratory of Immunology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, Telangana, 500 001, India.
Binay K
BK
Sahoo
Laboratory of Immunology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, Telangana, 500 001, India. manna@cdfd.org.in.
Sunil K
SK
Manna
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D000077185:Resveratrol; D016196:S Phase / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D051739:Microphthalmia-Associated Transcription Factor; D016328:NF-kappa B; D013267:Stilbenes; D000077185:Resveratrol
Apoptosis; MITF; Melanoma; NF-κB; Raf kinase; Resveratrol