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.
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Authors | Seung 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 |
Journal | International journal of oncology
(Int J Oncol)
Vol. 35
Issue 6
Pg. 1353-60
(Dec 2009)
ISSN: 1791-2423 [Electronic] Greece |
PMID | 19885558
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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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
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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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