2. Academic Validation
  3. Inhibition of SF3b1 by pladienolide B evokes cycle arrest, apoptosis induction and p73 splicing in human cervical carcinoma cells

Inhibition of SF3b1 by pladienolide B evokes cycle arrest, apoptosis induction and p73 splicing in human cervical carcinoma cells

  • Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):1273-1280. doi: 10.1080/21691401.2019.1596922.
Qianjing Zhang 1 2 3,  Cuixia Di 1 2 3,  Junfang Yan 1 2 3,  Fang Wang 1 2 3,  Tao Qu 4,  Yupei Wang 1 2 3,  Yuhong Chen 1 2 3,  Xuetian Zhang 1 2 3,  Yang Liu 1 2 3,  Hongying Yang 5,  Hong Zhang 1 2 3
Affiliations

Affiliations

  • 1 a Department of Radiation Medicine , Institute of Modern Physics, Chinese Academy of Sciences , Lanzhou , China.
  • 2 b Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences , Lanzhou , China.
  • 3 c School of Life Science , University of Chinese Academy of Sciences , Beijing , China.
  • 4 d Department of Biotherapy Center , Gansu Provincial Hospital , Lanzhou , China.
  • 5 e Medical School of Radiation Medicine and Protection, Medical College of Soochow , Soochow University , Suzhou , China.
PMID: 30963795 DOI: 10.1080/21691401.2019.1596922
Abstract

Pladienolide B is a potent Cancer cell growth inhibitor that targets the SF3B1 subunit of the spliceosome. There is considerable interest in the compound as a tool to study SF3B1 function in Cancer. However, so far little information is available on the molecular mechanism of SF3B1 eliciting Apoptosis in Cancer cells. Here, we investigated the molecular mechanism of SF3B1 eliciting Apoptosis in human cervical carcinoma cells. We demonstrated that inhibition of SF3B1 by pladienolide B inhibited proliferation of HeLa cells at low nanomolar concentrations in a dose- and time-dependent manner. It also induced G2/M phase arrest and significant rise of apoptotic cells. Moreover, it is indicated that inhibition of SF3B1 by pladienolide B induced Tap73/ΔNp73 expression and consequently down-regulated Bax/Bcl-2 ratio, cytochrome c release and Caspase-3 expression. Thus, our results showed that SF3B1 plays a pivotal role in cycle arrest, Apoptosis induction, and p73 splicing in human cervical carcinoma cells, suggesting that SF3B1 could be used as a potential candidate for cervical Cancer therapy.

Keywords

Alternative splicing; SF3b1; apoptosis; cancer; p73; pladienolide B.

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