Journal
BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume 35, Issue 8, Pages 1230-1237Publisher
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.b110535
Keywords
Panax Notoginseng Saponin; cisplatin; gap junction; connexin
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Funding
- National Natural Science Foundation of China [30973434, 30901807, 81001457]
- Natural Science Foundation of Provincial Education Department of Anhui [KJ2008A167]
- Fundamental Research Funds for the Central Universities, China [10YKPY32]
- Ministry of Health of China [2009ZX09303-007]
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Panax Notoginseng Saponins (PNS) have been well known to have anti-tumor activity and enhance cytotoxicity of some cancer chemotherapy agents, but the mechanisms underlying these effects are still unknown. This study investigates the effect of PNS on cytotoxicity of cisplatin and the relationship between this effect and the modulation of gap junctions (GJ) function by PNS in a transfected cell line. The cytotoxicity of cisplatin (0.25 1 mu g/mL) was increased in the presence of GJ. Inhibition of gap junction by either GJ blocker or interception of Connexin (Cx) expression decreased the cytotoxicity of cisplatin. Increasing GJ function enhanced cytotoxicity of cisplatin, only in the cells with functional GJ. PNS (50-200 mu g/mL) significantly enhanced cisplatin cytotoxicity, but this effect required functional gap junctions between the cells. Exposure of the cells to PNS (50-200 mu g/mL) for 4h leads to a significant enhance in dye coupling of GJ in a dose-dependent manner. These results suggest that PNS increases the cytotoxicity of cisplatin through enhancement of GJ activity.
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