Suppression of mTOR via Akt-dependent and -independent mechanisms in selenium-treated colon cancer cells: involvement of AMPKα1

Activation of the mammalian target of rapamycin (mTOR) pathway promotes tumorigenesis, and inhibiting the mammalian target of rapamycin complex 1 (mTORC1) has emerged as an attractive target for suppressing tumor growth. We found that selenium treatment of HT-29 colon cancer cells suppressed mTORC1 through Akt-independent and -dependent pathways. In Akt-independent mTORC1 inhibition in selenium-treated colon cancer cells, adenosine monophosphate-activated protein kinase (AMPK) alpha(1) was crucial for suppression of mTORC1 activity. In contrast, the Akt-dependent mTORC1 inhibition by selenium did not require AMPK alpha(1). The importance of the AMPK alpha(1)-mTORC1 pathway in mediating the antiproliferative action of selenium was examined in xenograft tumors, and the suppression of mTORC1 as well as Akt was concomitant with an increase in AMPK alpha(1) activity. These findings suggest that the antiproliferative effect of selenium is mediated by an Akt-independent AMPK alpha(1)/mTORC1 pathway or by the Akt/tuberous sclerosis complex 2 /mTORC1 pathway.