Solamargine induces apoptosis and sensitizes breast cancer cells to cisplatin.

Abstract

Solamargine (SM), a major steroidal alkaloid glycoside, was purified from Solanum incanum plant. SM exhibited the most cytotoxic effect comparing with that of cisplatin (cDDP), methotrexate (MTX), 5-fluorouracil (5-FU), epirubicin (EPI) and cyclophosphamide (CP) against human breast cancer cells. In this study, SM induces apoptosis of the breast cancer cells and the mechanism was characterized. SM up-regulated the expressions of external death receptors, such as tumor necrosis factor receptor I (TNFR-I), Fas receptor (Fas), TNFR-I-associated death domain (TRADD), and Fas-associated death domain (FADD). SM also enhanced the intrinsic ratio of Bax to Bcl-2 by up-regulating Bax and down-regulating Bcl-2 and Bcl-xL expressions. These effects resulted in the release of mitochondrial cytochrome c and activation of caspase-8, -9 and -3 in the cells, indicating that SM triggered extrinsic and intrinsic apoptotic pathways of breast cancer cells. Similar to function way of SM, cDDP causes cancer cell apoptosis though caspase-8/caspase-3 and Bax/cytochrome c pathways, but the resistance to cDDP is correlated with Bcl-2 and Bcl-xL overexpression. However, the overexpression of Bcl-2 and Bcl-xL can be broken through by SM. The combined treatment of SM and cDDP significantly reduced Bcl-2 and Bcl-xL expressions, and enhanced Bax, cytochrome c, caspase-9 and -3 expressions in breast cancer cells. Thus, the combined use of SM and cDDP may be effective in cDDP-resistant breast cancer.

• Authors: L Y Shiu, L C Chang, C H Liang, Y S Huang, H M Sheu, K W Kuo
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 45 Issue 11 Pg. 2155-64 (Nov 2007) ISSN: 0278-6915 [Print] England
• PMID: 17619073 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Solanaceous Alkaloids
• beta-solamarine
• Cisplatin

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy)
• Cell Line, Tumor
• Cisplatin (pharmacology)
• Down-Regulation
• Drug Synergism
• Female
• Gene Expression Regulation, Enzymologic
• Humans
• Inhibitory Concentration 50
• Signal Transduction
• Solanaceous Alkaloids (pharmacology)
• Up-Regulation