Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1783321726425235456 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5943942 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT ohtaekin fascaplysinsensitizesanticancereffectsofdrugstargetingaktandampk AT leejunho fascaplysinsensitizesanticancereffectsofdrugstargetingaktandampk AT kimseongman fascaplysinsensitizesanticancereffectsofdrugstargetingaktandampk AT namtaekjin fascaplysinsensitizesanticancereffectsofdrugstargetingaktandampk AT kimyoungseon fascaplysinsensitizesanticancereffectsofdrugstargetingaktandampk AT kimbyeongmo fascaplysinsensitizesanticancereffectsofdrugstargetingaktandampk AT yimwoojong fascaplysinsensitizesanticancereffectsofdrugstargetingaktandampk AT limjihong fascaplysinsensitizesanticancereffectsofdrugstargetingaktandampk |