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.
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.
Jeong
Seung Hun
SH
Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Medical Science Research Center, Busan 602-714, Korea.
Lee
Jee Suk
JS
Jeong
Na Young
NY
Kim
Tae Hyun
TH
Yoo
Ki Soo
KS
Song
Suhee
S
Suh
Hongsuk
H
Kwon
Taeg Kyu
TK
Park
Bong Soo
BS
Yoo
Young Hyun
YH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000187:drug effects*; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial; D018613:Microscopy, Confocal; D009284:Naphthols / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012118:Resorcinols / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
C523393:4-(6-hydroxy-2-naphthyl)-1,3-benzenediol; D000970:Antineoplastic Agents; D009284:Naphthols; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012118:Resorcinols; D013267:Stilbenes; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D000077185:Resveratrol