Anticancer activity of apple peel extracts against human breast cancer cells through insulin-like growth factor-1 signal transduction pathway

Insulin-like growth factor 1 receptor (IGF-1R) is an influential growth receptor in mammalian cells. Majority of cancers in humans shows an active IGF-1R signaling pathway. Apple peel extracts were investigated for their potential mechanisms of action against regulating cell proliferation in human breast cancer MDA-MB-231 cells under IGF-1 induction. Apple peel extracts significantly inhibited cellular proliferation in breast cancer cells in a dose-dependent manner at a dose ≥ 10 mg/mL. No cytotoxicity was observed in the human breast cancer MDA-MB-231 cells at the doses below 50.2 mg/mL. The IGF-1R/PI3K/Akt pathway expression was suppressed by apple peel extracts treatment. Expressions of cyclin D1-stimulating proteins NF-κ B and GSK-3β were inhibited, whereas p21 expression was upregulated. Apple peel extracts reduced the expression of cyclin D1, stagnating MDA-MB-231 cells in a G1 cell cycle arrest. Apple peel extracts stimulated PTEN, a tumor suppressor protein and an inhibitor of PI3K/Akt signaling pathway. The results suggested that apple peel extracts can induce inhibitory effects through downregulating IGF-1R/PI3K/Akt signal transduction pathway in human breast cancer MDA-MB-231 cells. This study shows the efficacy of apple peel extracts in reversing the IGF-1R signal transduction pathway, thereby hindering tumorigenesis in breast cancer cells.