Supplementary Figure 1. Lycorine has no apparent effect on body weight in nude mice; Supplementary Figure 2. Lycorine induces apoptosis via caspase-dependent pathway; Supplementary Figure 3. Lycorine induces autophagy in HuH-7 cells; Supplementary Figure 4. Inhibition of autophagy promotes the apoptotic effect of lycorine; Supplementary Figure 5. Lycorine promotes apoptosis and autophagy through repressing the Akt/mTOR pathway; Supplementary Figure 6. Lycorine promotes apoptosis and autophagy via TCRP1 pathway in HuH-7 cells; Supplementary Figure 7. The relevance between Akt and TCRP1 in HCC patient tissues; Supplementary Figure 8. Full scans of western-blot data shown in Figure 2; Supplementary Figure 9. Full scans of western-blot data shown in Figure 3; Supplementary Figure 10. Full scans of western-blot data shown in Figure 4; Supplementary Figure 11. Full scans of western-blot data shown in Figure 5; Supplementary Figure 12. Full scans of western-blot data shown in Figure 6.
ARTICLE ABSTRACT
Lycorine is a multifunctional bioactive compound, and it possesses potential anticancer activities. However, little is known about the underlying mechanism. In this research, we have found that lycorine significantly induces the apoptotic and autophagic capacities of hepatocellular carcinoma (HCC) cells in vitro and in vivo. Treatment with specific autophagy inhibitor (3-methyladenine/Bafilomycin A1) or knockdown of LC-3B/Atg5 by siRNA drastically enhances the apoptotic cell death effect by facilitating the switch from autophagy to apoptosis. Molecular validation mechanistically demonstrates that lycorine-induced apoptosis and autophagy in HCC cells is associated with decreased protein levels of tongue cancer resistance–associated protein 1 (TCRP1), and we further find that inhibition of TCRP1 decreases phosphorylation level of Akt and represses Akt/mTOR signaling. Finally, lycorine-induced apoptosis and autophagy suppress the growth of xenograft hepatocellular tumors without remarkable toxicity. Our results elucidate a novel molecular mechanism whereby lycorine promotes apoptosis and autophagy through the TCRP1/Akt/mTOR pathway in HCC. Our results reveal that lycorine might be a potential therapeutic agent for the treatment of HCC. Mol Cancer Ther; 16(12); 2711–23. ©2017 AACR.
