HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Knockdown of Bcl-xL enhances growth-inhibiting and apoptosis-inducing effects of resveratrol and clofarabine in malignant mesothelioma H-2452 cells.

Abstract
Mcl-1 and Bcl-xL, key anti-apoptotic proteins of the Bcl-2 family, have attracted attention as important molecules in the cell survival and drug resistance. In this study, we investigated whether inhibition of Bcl-xL influences cell growth and apoptosis against simultaneous treatment of resveratrol and clofarabine in the human malignant mesothelioma H-2452 cells. Resveratrol and clofarabine decreased Mcl-1 protein levels but had little effect on Bcl-xL levels. In the presence of two compounds, any detectable change in the Mcl-1 mRNA levels was not observed in RT-PCR analysis, whereas pretreatment with the proteasome inhibitor MG132 led to its accumulation to levels far above basal levels. The knockdown of Bcl-xL inhibited cell proliferation with cell accumulation at G2/M phase and the appearance of sub-G0/G1 peak in DNA flow cytometric assay. The suppression of cell growth was accompanied by an increase in the caspase-3/7 activity with the resultant cleavages of procaspase-3 and its substrate poly (ADP-ribose) polymerase, and increased percentage of apoptotic propensities in annexin V binding assay. Collectively, our data represent that the efficacy of resveratrol and clofarabine for apoptosis induction was substantially enhanced by Bcl-xL-lowering strategy in which the simultaneous targeting of Mcl-1 and Bcl-xL could be a more effective strategy for treating malignant mesothelioma.
AuthorsYoon-Jin Lee, In-Sung Hwang, Yong-Jin Lee, Chang-Ho Lee, Sung-Ho Kim, Hae-Saeon Nam, Young-Jin Choi, Sang-Han Lee
JournalJournal of Korean medical science (J Korean Med Sci) Vol. 29 Issue 11 Pg. 1464-72 (Nov 2014) ISSN: 1598-6357 [Electronic] Korea (South)
PMID25408576 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adenine Nucleotides
  • Antimetabolites, Antineoplastic
  • Arabinonucleosides
  • Leupeptins
  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • RNA, Messenger
  • RNA, Small Interfering
  • Stilbenes
  • bcl-X Protein
  • Clofarabine
  • Caspase 3
  • Caspase 7
  • Resveratrol
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde
Topics
  • Adenine Nucleotides (pharmacology)
  • Antimetabolites, Antineoplastic (pharmacology)
  • Apoptosis (drug effects)
  • Arabinonucleosides (pharmacology)
  • Caspase 3 (metabolism)
  • Caspase 7 (metabolism)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Clofarabine
  • G2 Phase Cell Cycle Checkpoints (drug effects)
  • Gene Knockdown Techniques
  • Humans
  • Leupeptins (pharmacology)
  • Lung Neoplasms (metabolism, pathology)
  • M Phase Cell Cycle Checkpoints (drug effects)
  • Mesothelioma (metabolism, pathology)
  • Mesothelioma, Malignant
  • Myeloid Cell Leukemia Sequence 1 Protein (antagonists & inhibitors, genetics, metabolism)
  • RNA Interference
  • RNA, Messenger (metabolism)
  • RNA, Small Interfering (metabolism)
  • Resveratrol
  • Stilbenes (pharmacology)
  • bcl-X Protein (antagonists & inhibitors, genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: