Sulforaphane regulates the proliferation of leukemia stem-like cells via Sonic Hedgehog signaling pathway

Abstract

Sulforaphane (SFN), the main ingredient in broccoli/broccoli sprouts, has a good anticancer effect in a wide variety of tumors, but whether SFN affects acute leukemia is not elucidated. Due to the self-renewal capability for leukemia stem cells, acute leukemia has a high relapse rate. This study explored the effects and related molecular mechanisms of SFN on the proliferation of leukemia stem-like cells in acute myeloid leukemia cells. We found that SFN inhibited the proliferation of leukemia stem-like cells in vitro and in vivo. Meanwhile, we observed that SFN could regulate the stem characteristic of leukemia cells. After SFN treatment, the expression of the key players in the Sonic Hedgehog (Shh) signaling pathway was significantly decreased at the transcriptional and protein levels. To further determine the contribution of the Shh signaling molecular mechanism to SFN-mediated self-renewal capability of LSCs, we then manipulated the Shh gene in the leukemia cells to either overexpress the gene using lentiviral vector transduction or knockdown the gene via siRNA. The results demonstrated that SFN suppressed proliferation in Shh-overexpressed cells more than in Shh-downregulated cells, suggesting that SFN negatively modulates proliferation of leukemia stem-like cells via affecting the Shh signaling pathway. Altogether, these results suggest that SFN is a potent anti-leukemia agent that has inhibitory effects on leukemia stem-like cells' proliferation by regulating the Shh signaling pathway.