Background:
Despite the success of herceptin, a significant proportion of HER-2 positive breast cancer patients responded poorly to the treatment. Curcumin (diferuloylmethane), derived from Curcuma longa L,
can inhibit the formation of tumors, induce apoptosis, and act on a variety of signal transduction pathways.
Objectives:We have hypothesized that the property of curcumin to downregulate EGFR, HER-2 oncoprotein, and signal transduction pathway of PI3K/Akt, and MAPK may be used in the treatment of HER-2 over expressed breast cancer.
Results: The combination of curcumin did not interfere with the action of herceptin. The herceptin sensitive BT-474 and herceptin resistant SKBr-3(hr) were all sensitive to curcumin treatment. In western blot analysis, the phosphorylation of HER-2, Akt, MAPK were reduced in BT-474 cells when treated with herceptin. In SKBr-3(hr) cells, the addition of herceptin did not downregulate the phosphorylation of HER-2, Akt, and MAPK. When treated with curcumin, the phosphorylation of HER-2, Akt, and MAPK of SKBr-3(hr) were decreased combined with the downregulation of HER-2 oncoprotein in a dose and time dependent manner.
Conclusions: The effectiveness of curcumin in the treatment of HER-2 overexpressed breast cancer was further confirmed through in vivo BT-474 xenograft model. The comparable ability of curcumin to inhibit cell proliferation, mobility, and angiogenesis as herceptin, combined with the potential ability to overcome the herceptin resistance, curcumin may be a novel agent in the treatment of HER-2 overexressed breast cancer.