Assessment of Cellular Apoptosis Induced by Hydroxychalcones in MCC13 Merkel Cells

Chalcones, as flavonoid precursors, are known to have biological importance and vast pharmacological effects. These bioactive molecules have been used in traditional medicine for many years for treatment of various diseases, particularly because of their antitumor activity. The aim of this study was to assess antiproliferative activity of selected hydroxychalcones against six cancer cell lines, derived from various human organs and with varying degrees of aggressiveness and resistance to cytostatics (5637, A-431, UM-SCC-17A, SK-MEL-3, MCC13, A172) in comparison to two noncancerous cell lines (MCF-10A and BALB/3T3). The specific goal of the present study was to assess the influence of 2′-hydroxychalcone, 4-hydroxychalcone and 4′-hydroxychalcone, the compounds with the same molar mass but with different positions of the hydroxyl group, on different stages of apoptosis. Additionally, we aimed to determine the involvement of mitochondria in the initiation of the cell death process. The principal cell line used for validation was Merkel cell carcinoma, a rare type of human skin cancer. The aforementioned compounds were supplemented for 24 and 48 h at several concentrations. In this paper we demonstrate the ability of hydroxychalcones to activate an early stage of apoptosis by exposure of phosphatidylserine on the cell surface with simultaneous changes in mitochondrial membrane. Our results acknowledge and strengthen the prospect of using chalcones for development of new therapeutic strategies in various oncological disease models.