User talk:Akundu040980

Melanoma
Indole-3-carbinol causes proliferation arrest and apoptosis in human melanoma cells. Kim YS et al showed that the master regulator of melanoma biology, Microphthalmia Associated Transcription factor (MITF-M) was downregulated by Indole-3-carinol to induce apoptosis [1]. Kundu A et al demonstrated that the anticancer property of Indole-3-carbinol is driven by specific targeting of oncogenic pathways [2,3]. In two different studies using xenografted mouse model of melanoma, they observed that subcutaneous injection of Indole-3-carbinol could bring down tumor burden significantly. The underlying molecular mechanism of this anti-tumor effect was found to be by the specific inhibition of activity of oncogenic BRAF V600E in tumors that harbored the mutation. However in tumors that expressed wild type BRAF, Indole-3-carbinol did not cause any comparable antiproliferative effect. Additionally Indole-3-carbinol did not cause antiproliferation even in normal epidermal melanocytes underscoring the specificity and selectivity of its action. Kundu et al further showed that inhibition of BRAF V600E activity by Indole-3-carbinol resulted in downregulation of MITF-M by downstream signaling which caused a G1 cell cycle arrest leading to the observed antiproliferative effect.

In a second study [3] Kundu et al showed that in melanoma cells where PTEN is downregulated, Indole-3-carbinol directly interacts with NEDD4_1 to prevent PTEN ubiquitination and subsequent proteasomal degradation. This results in stabilization of PTEN and inhibition of proliferation by downstream AKT signaling. Overall scientific evidence shows that in melanoma, Indole-3-carbinol specifically inhibits the two most commonly associated driver mutation signaling pathways to cause antiproliferation, a fact that can be used to design clinical trial to treat human patients with Indole-3-carbinol in future.