Schisandrin B enhances doxorubicin-induced apoptosis of cancer cells but not normal cells.
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.
Li
Ling
L
The Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, PR China.
Lu
Qinghua
Q
Shen
Yanwei
Y
Hu
Xun
X
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D034242:Cyclooctanes / Q000494:pharmacology; D017931:DNA Primers; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D034242:Cyclooctanes; D017931:DNA Primers; D017705:Lignans; D011083:Polycyclic Compounds; D012333:RNA, Messenger; C015499:schizandrin B; D004317:Doxorubicin; D020169:Caspases