RETRACTED: Heptazoline exerts antiproliferative effects on human melanoma cells by inducing apoptosis, cell cycle arrest and targeting MAPK signalling pathway (Retracted Article)

Purpose: Melanoma is one of the prevalent types of cancer and ranks 6th major cause of cancer associated mortality. In this study the anticancer effects of the carbazole alkaloid Heptazoline were investigated against a panel of melanoma cells. Methods: The normal BJ-5TA and melanoma cell lines MEL-CLS-1M MEL-CLS-2, MEL-CLS-3 were used in this study. MTT and colony formation assays were used to determine the proliferation rate of melanoma cells Aciridine orange (AO)/ ethidium bromide (EB) and annexin V/propidium iodide (PI) staining were used to check the apoptotic cell death. Cell cycle analysis was performed by flow cytometry and protein expression was checked by western blotting. Results: Heptazoline inhibited the growth of all the melanoma cell lines, exhibiting an IC50 of 15 to 40 mu M against the melanoma cells. However, the normal skin cells had IC50 125 mu M. The anticancer effects were found to be due to induction of apoptotic cell death which was associated with the upregulation of Bax, cleaved caspase 3, 9 and PARP and down regulation of Bcl-2. Furthermore, Heptazoline also triggered the G0/G1 arrest of melanoma cells. The effects of Heptazoline on the MAPK signalling pathway revealed that this molecule could inhibit the expression of p-p38 concentration-dependently. Conclusion: Taken together, Heptazoline may prove a lead molecule in the development of systemic therapy of melanoma.