Inhibition of mTORC1 releases the feedback inhibition mediated by the S6K1-IRS1-PI3K loop, which leads to activation of the AKT pathway in cancer.35 Accordingly, we inhibited the PI3K pathway using two specific inhibitors, wortmannin and LY294002, separately to check the status of AKT activation in mahanine-treated PTENwt cells. Here, IRS1 is linked to cancer.