The Impact of Panobinostat on Cell Death in Combination with S63845 in Multiple Myeloma Cells

Multiple myeloma is a B cell neoplasm characterized by bone marrow infiltration with malignant plasma cells. The Overexpression of histone deacetylase prevents apoptosis of myeloma cells by different mechanisms. The combination of Panobinostat with a BH3 mimetic, S63845, has demonstrated significant antitumor activity in multiple myeloma. We examined the impact of Panobinostat combined with MCL-1 inhibitor on multiple myeloma cell lines in vivo and in vitro as well as on fresh human myeloma cells. Our study shows that MCL-1 remains a major resistant factor to cell death induced by Panobinostat. Therefore, the inhibition of the MCL-1 member is considered a therapeutic strategy to kill the myeloma cells. We examined that the MCL-1 inhibitor (S63845) enhanced the cytotoxic effect of Panobinostat and decreased the viability of human cell lines and primary myeloma patient cells. Mechanistically, Panobinostat/S63845 control cell death via an intrinsic pathway. Given these data, the combination can be a promising therapeutic target for myeloma patients and should be further explored in clinical trials.