hs-1793 and Leukemia--Promyelocytic--Acute

Bcl-2 protects cancer cells from the apoptotic effects of various chemotherapeutic agents. Inhibition or downregulation of Bcl-2 represents a new therapeutic approach to bypass chemoresistance in cancer cells. Previously we designed and synthesized the resveratrol analogue HS-1793 displaying stronger antitumor efficacy than resveratrol and further demonstrated the HS-1793 resistance conferred by Bcl-2 in human leukemic U937 cells. We undertook this study to determine if HS-1793 treatment can bypass the anti-apoptotic effects of Bcl-2 in human renal cancer cells, with a specific focus on the involvement of promyelocytic leukemia nuclear bodies (PML-NBs). Experiments were conducted with Bcl-2-overexpressing human renal clear cell carcinoma Caki-1 cells. Various apoptosis assessment assays demonstrated that HS-1793 overcomes the resistance conferred by Bcl-2 in Caki-1 cells by inducing apoptosis. We elucidated that HS-1793-induced formation of mature promyelocytic leukemia (PML) nuclear bodies (NBs) correlates with overcoming the anti-apoptotic effects of Bcl-2 in Caki-1 cells. Our findings show that the resveratrol analogue HS-1793 might provide a novel promising strategy for overcoming the resistance conferred by Bcl-2 via PML protein and the formation of mature PML-NBs.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Renal Cell; Cell Line, Tumor; Drug Resistance, Neoplasm; Flow Cytometry; Fluorescent Antibody Technique; Humans; Intranuclear Inclusion Bodies; Kidney Neoplasms; Leukemia, Promyelocytic, Acute; Membrane Potential, Mitochondrial; Microscopy, Confocal; Naphthols; Nuclear Proteins; Promyelocytic Leukemia Protein; Proto-Oncogene Proteins c-bcl-2; Resorcinols; Resveratrol; Stilbenes; Transcription Factors; Tumor Suppressor Proteins