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A novel resveratrol analogue HS-1793 treatment overcomes the resistance conferred by Bcl-2 and is associated with the formation of mature PML nuclear bodies in renal clear cell carcinoma Caki-1 cells.

Abstract
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.
AuthorsSeung Hun Jeong, Jee Suk Lee, Na Young Jeong, Tae Hyun Kim, Ki Soo Yoo, Suhee Song, Hongsuk Suh, Taeg Kyu Kwon, Bong Soo Park, Young Hyun Yoo
JournalInternational journal of oncology (Int J Oncol) Vol. 35 Issue 6 Pg. 1353-60 (Dec 2009) ISSN: 1791-2423 [Electronic] Greece
PMID19885558 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 4-(6-hydroxy-2-naphthyl)-1,3-benzenediol
  • Antineoplastic Agents
  • Naphthols
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • Proto-Oncogene Proteins c-bcl-2
  • Resorcinols
  • Stilbenes
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human
  • Resveratrol
Topics
  • Antineoplastic Agents (pharmacology)
  • Apoptosis (drug effects, physiology)
  • Carcinoma, Renal Cell (metabolism, pathology)
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm (drug effects, physiology)
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Intranuclear Inclusion Bodies (drug effects)
  • Kidney Neoplasms (metabolism, pathology)
  • Leukemia, Promyelocytic, Acute (metabolism, pathology)
  • Membrane Potential, Mitochondrial
  • Microscopy, Confocal
  • Naphthols (pharmacology)
  • Nuclear Proteins (metabolism)
  • Promyelocytic Leukemia Protein
  • Proto-Oncogene Proteins c-bcl-2 (metabolism)
  • Resorcinols (pharmacology)
  • Resveratrol
  • Stilbenes (pharmacology)
  • Transcription Factors (metabolism)
  • Tumor Suppressor Proteins (metabolism)

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