A combination of semi-purified L-methioninase with tamoxifen citrate to ameliorate breast cancer in athymic nude mice.

ABSTRACT

BACKGROUND: Chemotherapy nonspecifically targets both tumor and healthy proliferating cells. Methionine deprivation using L-methioninase along with chemotherapy appears promising towards cancer management. The present study is an attempt to use a new combination of L-methioninase with Tamoxifen (TAM) to treat breast cancer in mice. METHODS AND RESULTS: L-Methioninase from Methylobacterium sp. was partially purified (SPMet's) by cold acetone precipitation and lyophilized. Its cytotoxicity effect, alone and in combination with Tamoxifen, was evaluated in vitro (MCF-7) cells and in vivo (athymic nude mice) conditions. SPMet's was found to inhibit the growth of MCF-7 cells with an IC50 value of 47.05 µg/ml, while the combination of SPMet's and TAM had an IC50 of 6.4 µg/ml. Athymic nude mice were grouped into Group-I - Tumor control; Group-II - TAM; Group-III - SPMet's; Group-IV - SPMet's + TAM. Tumor growth inhibition (TGI) was maximum in Group-IV with 84.65% followed by Group-II with 65.12%. Hematological and Biochemical parameters in Group-II, III, and IV were restored to normal levels. Tumor histopathology showed increased apoptosis and necrosis in Group-IV. Caspases 3 & 8 gene upregulation was significantly higher in Group-IV than other treated groups, indicating higher efficacy of the combination approach. CONCLUSION: This is the first study report about a combination of SPMet's and TAM on in vivo breast cancer model, with significantly higher anticancer activity and without noticeable side effects. The findings of this study have several important implications for future clinical studies.