Targeting neddylation pathway with MLN4924 (Pevonedistat) induces NOXA-dependent apoptosis in renal cell carcinoma (VSports app下载)

Jiyou Wang¹, Shiwen Wang², Wenjuan Zhang³, Xiaofang Wang³, Xiaojun Liu³, Liang Liu³, Lihui Li³, Yupei Liang³, Jinha Yu⁴, Lak Shin Jeong⁴, Lijun Jia⁵, Hu Zhao⁶, Yanmei Zhang⁷

Affiliations

¹ Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China; College of Life Science, Dezhou University, Dezhou, 253023, China.
² Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China; Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, 200040, China; Research Center on Aging and Medicine, Fudan University, Shanghai, 200040, China.
³ Cancer Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
⁴ College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
⁵ Cancer Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
⁶ Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China; Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, 200040, China; Research Center on Aging and Medicine, Fudan University, Shanghai, 200040, China. Electronic address: hubertzhao@qiuluzeuv.cn.
⁷ Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China; Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, 200040, China; Research Center on Aging and Medicine, Fudan University, Shanghai, 200040, China. Electronic address: 1518653286@qiuluzeuv.cn.

PMID: 28669728
DOI: 10.1016/j.bbrc.2017.06.179

"VSports最新版本" Targeting neddylation pathway with MLN4924 (Pevonedistat) induces NOXA-dependent apoptosis in renal cell carcinoma

Jiyou Wang (VSports最新版本) et al. Biochem Biophys Res Commun. 2017.

. 2017 Sep 2;490(4):1183-1188.

doi: 10.1016/j.bbrc.2017.06.179. Epub 2017 Jun 29.

Authors

Jiyou Wang¹, Shiwen Wang², Wenjuan Zhang³, Xiaofang Wang³, Xiaojun Liu³, Liang Liu³, Lihui Li³, Yupei Liang³, Jinha Yu⁴, Lak Shin Jeong⁴, Lijun Jia⁵, Hu Zhao⁶, Yanmei Zhang⁷

Affiliations

¹ Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China; College of Life Science, Dezhou University, Dezhou, 253023, China.
² Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China; Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, 200040, China; Research Center on Aging and Medicine, Fudan University, Shanghai, 200040, China.
³ Cancer Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
⁴ College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
⁵ Cancer Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
⁶ Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China; Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, 200040, China; Research Center on Aging and Medicine, Fudan University, Shanghai, 200040, China. Electronic address: hubertzhao@qiuluzeuv.cn.
⁷ Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China; Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, 200040, China; Research Center on Aging and Medicine, Fudan University, Shanghai, 200040, China. Electronic address: 1518653286@qiuluzeuv.cn.

PMID: 28669728
DOI: 10.1016/j.bbrc.2017.06.179

Abstract

Inhibition of protein neddylation pathway has emerged an attractive anticancer strategy in preclinical studies by using Nedd8-activating enzyme (NAE) inhibitor MLN4924 (Pevonedistat). Previous studies have reported the antitumor activity of MLN4924 mediated by its efficacy on apoptosis, autophagy and senescence. However, whether MLN4924 has any effect on renal carcinoma cells (RCC) remains unexplored. Here we reported that MLN4924 specifically inhibited protein neddylation pathway, leading to statistically significantly suppress the proliferation, survival and migration of RCC cells by inducing G2 cell-cycle arrest, followed by apoptosis in a MLN4924 dose-dependent manner. Further mechanistic study revealed that MLN4924-induced apoptosis was mediated by substantial up-regulation of pro-apoptotic NOXA. These findings highlighted the anticancer effects of the neddylation inhibitors (e VSports手机版. g. MLN4924) for the treatment of RCC. .

Keywords: Apoptosis; MLN4924; Neddylation; Renal cell carcinoma. V体育安卓版.

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Targeting neddylation pathway with MLN4924 (Pevonedistat) induces NOXA-dependent apoptosis in renal cell carcinoma (VSports app下载)

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"VSports最新版本" Targeting neddylation pathway with MLN4924 (Pevonedistat) induces NOXA-dependent apoptosis in renal cell carcinoma

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