Quercetin is a dietary flavonoid which exerts anti-oxidant, anti-inflammatory and anti-cancer properties. In this study, we investigated the anti-proliferative effect of quercetin in two breast cancer cell lines (MCF-7 and MDA-MB-231), which differed in hormone receptor. IC50 value (37μM) of quercetin showed significant cytotoxicity in MCF-7 cells, which was not observed in MDA-MB-231 cells even at 100μM of quercetin treatment. To study the response of cancer cells to quercetin, with respect to different hormone receptors, both the cell lines were treated with a fixed concentration (40μM) of quercetin. MCF-7 cells on quercetin treatment showed more apoptotic cells with G1 phase arrest. In addition, quercetin effectively suppressed the expression of CyclinD1, p21, Twist and phospho p38MAPK, which was not observed in MDA-MB-231 cells. To analyse the molecular mechanism of quercetin in exerting an apoptotic effect in MCF-7 cells, Twist was over-expressed and the molecular changes were observed after quercetin administration. Quercetin effectively regulated the expression of Twist, in turn p16 and p21 which induced apoptosis in MCF-7 cells. In conclusion, quercetin induces apoptosis in breast cancer cells through suppression of Twist via p38MAPK pathway.

Twist is a basic helix-loop-helix transcription factor family normally expressed during embryonic development and apparently activated in variety of tumours. Overexpression of twist is correlated with uncontrolled cell proliferation, differentiation, invasion and metastasis. Twist expression is associated with oestrogen receptor (ER); however, the molecular mechanism behind involvement of twist in progression of breast cancer is still unclear. Nitric oxide synthases (NOSs) which cause damage to the cellular DNA are also shown to be involved in cancer progression. The present study involves total number of n = 85 breast biopsies, which include 19 non-cancer and 66 cancerous lesions. We analysed twist, iNOS and ER expression pattern in human breast carcinomas by RT-PCR and also analysed twist cellular localisation by immunohistochemical analysis. iNOS expression pattern was correlated with different stages of breast carcinoma. Twist expression was significantly increased in cancer lesions when compared to the non-cancer. The breast cancer lesions positive to ER showed positivity to twist (72%) as well. The higher stages of cancer lesions showed a significant expression of twist localised in cytoplasm of the cancer cells. Collectively these data indicate that up-regulation of twist is correlated with the ER presenting breast cancer, and iNOS expression was positively correlated with tumour-node metastasis (TNM) staging of breast cancer. These findings suggest that expression of twist and iNOS may have a functional role in cancer progression.