Anti-carcinogenic effects of Morinda citrifolia (noni): identifying signal transduction pathways using ER positive and ER negative human breast cancer cell lines

Abstract

It is predicted that one in every eight women in the United States will be diagnosed with breast cancer in her lifetime, making breast cancer the second most prevalent cancer in the nation. Native Hawaiians have the highest incidence as well as mortality rates compared to other ethnic groups in Hawaii. An increase in the use of alternative medicine, specifically by breast cancer patients prompted us to study the anti-cancer effects of Hawaiian traditional medicine, Morinda citritfolia (noni). Estrogen receptor positive (ER +ve) cells, MCF-7 and estrogen receptor negative (ER--ve) cells, MDAMB-231 were initially treated with fNJ at varying concentrations for up to 96h. 10% fNJ demonstrated cell death in 30--40% of the cells and 15% fNJ demonstrated cell death in 50--60% of the cells. In addition, when non-carcinoma breast cells, MCF-10A underwent the same treatment, 15% fNJ only demonstrated 10--15% cell death in MCF-10A. Cell proliferation assays suggest that fNJ is toxic to breast cancer cell lines, MCF-7 and MDAMB-231 but not normal breast cell line, MCF-10A. Apoptosis array data have shown a significant decrease of a class of proteins called inhibitors of apoptosis proteins (IAPs) such as survivin, Bcl-2, cIAP-1, and cIAP-2 in fNJ treated MCF-7 and MDAMB-231 cells. There was also a significant decrease in proteins that assist with cell replication such as claspin and phospho-Rad17. This demonstrates that fNJ induces cell selective apoptosis and inhibits cell proliferation in breast cancer cell lines, MCF-7 and MDAMB-231. [Grants: NCCAM (R21AT003719), USDA-CREES (2004-34135-15182)]