Delineation of proapoptotic signaling of anthracene-shelled M 2 L 4 metallacapsules and their synergistic activity with curcumin in cisplatin-sensitive and resistant tumor cell lines

In this study, we provide an oncopharmacological evaluation of the Pt(II)- and Pd(II)-clipped M2L4 nanocapsules; we report a thorough analysis of their synergistic effects in combined treatments with the pleiotropic anticancer agent curcumin. We examined changes in cellular expression of several apoptosis-related proteins in a panel of tumor cell lines with different chemosensitivity towards cisplatin, i.e. HT-29, HL-60 and its resistant strains HL-60/CDDP and HL-60/Dox, in order to assess the molecular mechanisms of their antitumor activity The results of the immunoassay concluded activation of the mitochondrial apoptotic pathway in all the screened tumor lines. A prevalent modulation of the extrinsic apoptotic signaling cascade was observed in the chemoresistant variants. Curcumin interactions of the tested compounds were estimated against the cisplatin-refractory cell line HT-29 via the Chou-Talalay method (CTM), whereby the palladium species yielded superior synergistic activity as compared to their platinum analogues.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research