Solamargine induces apoptosis and sensitizes breast cancer cells to cisplatin

Food Chem Toxicol. 2007 Nov;45(11):2155-64. doi: 10.1016/j.fct.2007.05.009. Epub 2007 May 24.

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.

MeSH terms

  • 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

Substances

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