Proteasome Inhibitor YSY01A Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant Human Ovarian Cancer Cells

Proteasome Inhibitor YSY01A Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant Human Ovarian Cancer Cells

Cisplatin is one of the most common drugs used for treatment of solid tumors such as ovarian cancer. Unfortunately, the development of resistance against this cytotoxic agent limits its clinical use. Here we report that YSY01A, a novel proteasome inhibitor, is capable of suppressing survival of cisp...

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Main Authors: Huang, Wei, Zhou, Quan, Yuan, Xia, Ge, Ze-mei, Ran, Fu-xiang, Yang, Hua-yu, Qiang, Guang-liang, Li, Run-tao, Cui, Jing-rong
Format: Online
Language:English
Published: Ivyspring International Publisher 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911881/
id pubmed-4911881
recordtype oai_dc
spelling pubmed-49118812016-06-20 Proteasome Inhibitor YSY01A Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant Human Ovarian Cancer Cells Huang, Wei Zhou, Quan Yuan, Xia Ge, Ze-mei Ran, Fu-xiang Yang, Hua-yu Qiang, Guang-liang Li, Run-tao Cui, Jing-rong Research Paper Cisplatin is one of the most common drugs used for treatment of solid tumors such as ovarian cancer. Unfortunately, the development of resistance against this cytotoxic agent limits its clinical use. Here we report that YSY01A, a novel proteasome inhibitor, is capable of suppressing survival of cisplatin-resistant ovarian cancer cells by inducing apoptosis. And YSY01A treatment enhances the cytotoxicity of cisplatin in drug-resistant ovarian cancer cells. Specifically, YSY01A abrogates regulatory proteins important for cell proliferation and anti-apoptosis including NF-κB p65 and STAT3, resulting in down-regulation of Bcl-2. A dramatic increase in cisplatin uptake was also observed by inductively coupled plasma-mass spectrometry following exposure to YSY01A. Taken together, YSY01A serves as a potential candidate for further development as anticancer therapeutics targeting the proteasome. Ivyspring International Publisher 2016-06-06 /pmc/articles/PMC4911881/ /pubmed/27326257 http://dx.doi.org/10.7150/jca.14519 Text en © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Huang, Wei
Zhou, Quan
Yuan, Xia
Ge, Ze-mei
Ran, Fu-xiang
Yang, Hua-yu
Qiang, Guang-liang
Li, Run-tao
Cui, Jing-rong
spellingShingle Huang, Wei
Zhou, Quan
Yuan, Xia
Ge, Ze-mei
Ran, Fu-xiang
Yang, Hua-yu
Qiang, Guang-liang
Li, Run-tao
Cui, Jing-rong
Proteasome Inhibitor YSY01A Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant Human Ovarian Cancer Cells
author_facet Huang, Wei
Zhou, Quan
Yuan, Xia
Ge, Ze-mei
Ran, Fu-xiang
Yang, Hua-yu
Qiang, Guang-liang
Li, Run-tao
Cui, Jing-rong
author_sort Huang, Wei
title Proteasome Inhibitor YSY01A Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant Human Ovarian Cancer Cells
title_short Proteasome Inhibitor YSY01A Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant Human Ovarian Cancer Cells
title_full Proteasome Inhibitor YSY01A Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant Human Ovarian Cancer Cells
title_fullStr Proteasome Inhibitor YSY01A Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant Human Ovarian Cancer Cells
title_full_unstemmed Proteasome Inhibitor YSY01A Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant Human Ovarian Cancer Cells
title_sort proteasome inhibitor ysy01a enhances cisplatin cytotoxicity in cisplatin-resistant human ovarian cancer cells
description Cisplatin is one of the most common drugs used for treatment of solid tumors such as ovarian cancer. Unfortunately, the development of resistance against this cytotoxic agent limits its clinical use. Here we report that YSY01A, a novel proteasome inhibitor, is capable of suppressing survival of cisplatin-resistant ovarian cancer cells by inducing apoptosis. And YSY01A treatment enhances the cytotoxicity of cisplatin in drug-resistant ovarian cancer cells. Specifically, YSY01A abrogates regulatory proteins important for cell proliferation and anti-apoptosis including NF-κB p65 and STAT3, resulting in down-regulation of Bcl-2. A dramatic increase in cisplatin uptake was also observed by inductively coupled plasma-mass spectrometry following exposure to YSY01A. Taken together, YSY01A serves as a potential candidate for further development as anticancer therapeutics targeting the proteasome.
publisher Ivyspring International Publisher
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911881/
_version_ 1613596262073892864

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