Schisandrin B enhances doxorubicin-induced apoptosis of cancer cells but not normal cells.

Abstract

The dose-dependent cardiotoxicities of doxorubicin (DOX) significantly limits its anti-cancer efficacies. One of the ways to augment the efficacies of DOX at a relatively low cumulative dose is to use a chemical sensitizer. Here, we demonstrated that schisandrin B (Sch B) significantly enhanced DOX-induced apoptosis of SMMC7721, a human hepatic carcinoma cell line, and of MCF-7, a human breast cancer cell line. This enhancement was irrelevant to the action of Sch B on P-glycoprotein or other drug-transporters, but associated with the activation of caspase-9 rather than caspase-8. The loss of mitochondria membrane potential was observed when cells were treated with DOX and Sch B combined. On the other hand, at the same experimental conditions, Sch B did not enhance the DOX-induced apoptosis of primary rat cardiomyocytes and primary human fibroblasts. Therefore, it is speculative that Sch B may bring benefit to clinical chemotherapy by reducing significantly the cumulative doses of DOX and its associated cardiotoxicities.

• Authors: Ling Li, Qinghua Lu, Yanwei Shen, Xun Hu
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 71 Issue 5 Pg. 584-95 (Feb 28 2006) ISSN: 0006-2952 [Print] England
• PMID: 16405922 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents
• Cyclooctanes
• DNA Primers
• Lignans
• Polycyclic Compounds
• RNA, Messenger
• schizandrin B
• Doxorubicin
• Caspases

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Base Sequence
• Caspases (metabolism)
• Cell Line, Tumor
• Cells, Cultured
• Cyclooctanes (pharmacology)
• DNA Primers
• Doxorubicin (pharmacology)
• Drug Synergism
• Flow Cytometry
• Humans
• Lignans (pharmacology)
• Polycyclic Compounds (pharmacology)
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction