**4. Conclusions**

Salternamide A was identified for the first time as an inhibitor of HIF-1α accumulation under hypoxic conditions in cancer cells (Figure 6). The translational regulation of HIF-1α accumulation by SA was partly associated with the down-regulation of the axis of the PI3K/mTOR/STAT3 signaling pathways. The anti-proliferative activity of SA in HCT116 colorectal cancer cells was also associated with G2/M cell cycle arrest and apoptotic/autophagic cell deaths. Therefore, SA is a leading candidate for the development of anticancer agents, and these mechanisms will be a key therapeutic target for pharmacologic and therapeutic intervention in HIF-1α-driven tumor growth and cell death.

**Figure 6.** Proposed signaling pathways underlying the effects of SA on the suppression of HIF-1α and the induction of cell death in human colorectal cancer cells.

**Acknowledgments:** This work was supported by a National Research Foundation (NRF) grant funded by the Korean government (MEST) (NRF No. 2009-0083533) and a grant from the MarineBio Research Program of the NRF (NRF No. 2012-0006712).

**Author Contributions:** Duc-Hiep Bach and Sang Kook Lee conceived and designed the experiments; Duc-Hiep Bach performed the experiments; Seong-Hwan Kim and Dong-Chan Oh isolated the compound; Duc-Hiep Bach, Ji-Young Hong, Hyen Joo Park, and Sang Kook Lee analyzed the data; Duc-Hiep Bach, Ji-Young Hong, and Sang Kook Lee wrote the paper.

**Conflicts of Interest:** The authors declare no conflict of interest.
