The Target Differences of Anti-Tumorigenesis Potential of Curcumin and its Analogues Against HER-2 Positive and Triple-Negative Breast Cancer Cells

Abstract

<b><i>Purpose:</i></b> The current study aims to evaluate the <i>in vitro</i> cytotoxic and cell migration effects of synthetic curcumin and its analogues on HER2 and nuclear factor kappa B (NFκB) pathways, as well as the in vivo inhibitory effect on cancer growth of metastatic breast cancer. <b><i>Methods:</i></b> Cell viability, protein expression, and protein localization were determined <i>in vitro</i> using MTT assay, western blotting, and immunofluorescence, respectively. Meanwhile, scratch wound healing assay and gelatin zymography were conducted to investigate the metastasis inhibitory effect. The <i>in vivo</i> anti-tumor ability was evaluated in xenograft mouse model using triple-negative breast cancer (TNBC) cells. <b><i>Results:</i></b> Curcumin, PGV-0, and PGV-1 exhibited cytotoxic effect against HER2-overexpressing breast cancer cells. Although PGV-1 showed the best activity in the single cytotoxic assay, curcumin showed the strongest synergism with doxorubicin. Curcumin and PGV-0 inhibited membrane localization of HER2. In contrast, PGV-1 neither inhibited localization nor decreased the expression of HER2, nonetheless showed the most potent inhibition against nuclear localization of p65 indicating the different mechanisms of curcumin, PGV-0, and PGV-1. Regarding cancer metastasis, curcumin and PGV-1 showed inhibitory activities against cell migration and inhibited MMP-2 and MMP-9 protein expression. Lastly, PGV-1 was more potent compared to curcumin to suppress the tumor formation of metastatic breast cancer xenograft model in nude mice. <b><i>Conclusion:</i></b> Overall, our study strengthens the potency of curcumin analogue, PGV-1, for treating several types of cancer, including metastatic breast cancer.