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

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 increase...

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Autores principales: Oh, Taek-In, Lee, Jun Ho, Kim, Seongman, Nam, Taek-Jin, Kim, Young-Seon, Kim, Byeong Mo, Yim, Woo Jong, Lim, Ji-Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943942/
https://www.ncbi.nlm.nih.gov/pubmed/29295560
http://dx.doi.org/10.3390/molecules23010042
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author Oh, Taek-In
Lee, Jun Ho
Kim, Seongman
Nam, Taek-Jin
Kim, Young-Seon
Kim, Byeong Mo
Yim, Woo Jong
Lim, Ji-Hong
author_facet Oh, Taek-In
Lee, Jun Ho
Kim, Seongman
Nam, Taek-Jin
Kim, Young-Seon
Kim, Byeong Mo
Yim, Woo Jong
Lim, Ji-Hong
author_sort Oh, Taek-In
collection PubMed
description 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.
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spelling pubmed-59439422018-11-13 Fascaplysin Sensitizes Anti-Cancer Effects of Drugs Targeting AKT and AMPK Oh, Taek-In Lee, Jun Ho Kim, Seongman Nam, Taek-Jin Kim, Young-Seon Kim, Byeong Mo Yim, Woo Jong Lim, Ji-Hong Molecules Article 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. MDPI 2017-12-24 /pmc/articles/PMC5943942/ /pubmed/29295560 http://dx.doi.org/10.3390/molecules23010042 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Oh, Taek-In
Lee, Jun Ho
Kim, Seongman
Nam, Taek-Jin
Kim, Young-Seon
Kim, Byeong Mo
Yim, Woo Jong
Lim, Ji-Hong
Fascaplysin Sensitizes Anti-Cancer Effects of Drugs Targeting AKT and AMPK
title Fascaplysin Sensitizes Anti-Cancer Effects of Drugs Targeting AKT and AMPK
title_full Fascaplysin Sensitizes Anti-Cancer Effects of Drugs Targeting AKT and AMPK
title_fullStr Fascaplysin Sensitizes Anti-Cancer Effects of Drugs Targeting AKT and AMPK
title_full_unstemmed Fascaplysin Sensitizes Anti-Cancer Effects of Drugs Targeting AKT and AMPK
title_short Fascaplysin Sensitizes Anti-Cancer Effects of Drugs Targeting AKT and AMPK
title_sort fascaplysin sensitizes anti-cancer effects of drugs targeting akt and ampk
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943942/
https://www.ncbi.nlm.nih.gov/pubmed/29295560
http://dx.doi.org/10.3390/molecules23010042
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