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Fascaplysin Sensitizes Anti-Cancer Effects of Drugs Targeting AKT and AMPK

Fascaplysin Sensitizes Anti-Cancer Effects of Drugs Targeting AKT and AMPK

Taek-In Oh, Jun Ho Lee, Seongman Kim, Taek-Jin Nam, Young-Seon Kim, Byeong Mo Kim, Woo Jong Yim, Ji-Hong Lim

Molecules. 2017 Dec 24;23(1):42.

PMID: 29295560

Abstract:

Fascaplysin, a natural product isolated from marine sponges, is a potential candidate for the development of anti-cancer drugs. However, the mechanism underlying its therapeutic effect of strengthening anti-cancer efficacy of other drugs is poorly understood. Here, we found that fascaplysin increases phosphorylation of protein kinase B (PKB), also known as AKT, and adenosine monophosphate-activated protein kinase (AMPK), which are considered therapeutic targets for cancer treatment due to their anti-apoptotic or pro-survival functions in cancer. A cell viability assay revealed that pharmacological suppression of AKT using LY294002 enhanced the anti-cancer effect of fascaplysin in various cancer cells. Similarly, fascaplysin was observed to have improved anti-cancer effects in combination with compound C, a selective AMPK inhibitor. Another challenge showed that fascaplysin increased the efficacy of methotrexate (MTX)-mediated cancer therapy by suppressing genes related to folate and purine metabolism. Overall, these results suggest that fascaplysin may be useful for improving the anti-cancer efficacy of targeted anti-cancer drugs, such as inhibitors of phosphoinositide 3-kinase AKT signaling, and chemotherapeutic agents, such as MTX.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP2410937	Methotrexate Related Compound C		2410-93-7	Price

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