The Activity of Trisindoline 5 Compound againsts c-Myc and FoxO1, 3, 4 Gene Expression on MDA-MB-231 Breast Cancer Stem Cells

Unoptimum curing and controlling proliferation of cancer cells in breast is due to the presence of BCSCs (Breast cancer stem cells), which are associated with stemness, self-renewal, tumour initiation and metastasis. Similarly, overexpression of c-Myc (oncogenic transcription factor) in breast cancer has become potential as target of cancer therapy. Inhibition of c-Myc in cancer cells can increase the transcription factors FoxO family members including FoxO1, 3, 4 and their target genes involved in apoptosis, cell cycle arrest and autophagy. Trisindoline is an indole timer alkaloid natural compound, which is toxic to cancer cells. For this reason, we aim to decide the activity of one of derivate compound of trisindoline, namely as trisindoline 5 on BCSCs MDA-MB-231 through cytotoxicity, apoptosis, and gene expression of c-Myc and FoxO1, 3, 4. As a result, MTT assay showed trisindoline 5 can decrease the viability of BCSCs MDA-MB-231 with IC50 13.127µg/ml. Furthermore, flow cytometry analysis shown that trisindoline 5 can induce apoptosis 5.23% at concentration of 25µg/ml. Similarly, qPCR analysis showed the highest decrease in c-Myc was found in trisindoline 5 concentration of 25µg/ml with 0.0746-fold. Meanwhile, the highest increase FoxO1, 3, 4 expression was found in trisindoline 5 concentration of 25µg/ml, 20.6452-fold, 26.4709-fold, and 12.8341-fold respectively. Therefore, we conclude that trisindoline 5 concentration of 25µg/ml was able to decrease the expression of c-Myc and increase the expression of FoxO1, 3, 4 despites, it was not effective enough in reducing the population of BCSCs MDA-MB-231.