Ophiopogonin D' induces necroptosis in prostate cancer PC3 cells through RIP1/MLKL pathway

Jiajia Wang; Zongliang Lu; Ya Kong; Wei Song; He Wang; Hongxia Xu

doi:10.16016/j.1000-5404.201609037

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Ophiopogonin D' induces necroptosis in prostate cancer PC3 cells through RIP1/MLKL pathway

更新时间：2026-01-09

- Ophiopogonin D' induces necroptosis in prostate cancer PC3 cells through RIP1/MLKL pathway
- Journal of Third Military Medical University Vol. 39, Issue 3, Pages: 201-207(2017)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(81603347)
- DOI：10.16016/j.1000-5404.201609037
  CLC：
- Received：05 September 2016，
  
  Published：15 February 2017
- 稿件说明：
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Jiajia Wang, Zongliang Lu, Ya Kong, et al. Ophiopogonin D' induces necroptosis in prostate cancer PC3 cells through RIP1/MLKL pathway[J]. Journal of Third Military Medical University, 2017, 39(3): 201-207.
DOI：

Jiajia Wang, Zongliang Lu, Ya Kong, et al. Ophiopogonin D' induces necroptosis in prostate cancer PC3 cells through RIP1/MLKL pathway[J]. Journal of Third Military Medical University, 2017, 39(3): 201-207. DOI： 10.16016/j.1000-5404.201609037.

摘要

Abstract

Objective

To determine the anti-tumor effect of Ophiopogonin D' (OPD')

a natural saponin compound

against androgen-independent prostate cancer PC3 cells

and investigate the underlying mechanism.

Methods

PC3 cells were treated with different concentrations of OPD' (0

2.5

5 and 10 μmol/L). MTT assay

flow cytometry

Western blotting

crystal violet staining

and transmission electron microscopy were used to investigate the effects of OPD' on cell viability

Caspase-independent cell death

necroptosis

expression levels of necroptosis related proteins

receptor interacting protein-1 (RIP1) and mixed lineage kinase domain-like protein (MLKL)

and morphological changes

respectively.

Results

OPD' treatment significantly inhibited the growth in PC3 cells

ith 24-hour IC

of 6.25±0.31 μmol/L. OPD' treatment of 5 μmol/L for 24 h could induce necrosis in PC3 cells. Meanwhile

OPD' treatment of 5 μmol/L for 6 h induced late apoptosis/necrosis in a time-dependent manner (

=0.728

0.001). OPD' also induced Caspase-independent cell death in PC3 cells

which could be inhibited by necrostatin-1 (Nec-1)

a specific inhibitor of necroptosis (

=0.047). This indicated that OPD' induced necroptosis in PC3 cells. OPD' reduced the expression levels of Cleaved-RIP1

while increased the levels of RIP1 and p-MLKL in PC3 cells

and the expression of p-MLKL was elevated in a time-dependent manner (

=0.907

=0.005). Morphological observation displayed that OPD' induced necrosis-like changes in PC3 cells.

Conclusion

OPD' exerts obvious anti-cancer effects by inhibiting cell viability in prostate cancer cells

and through activating RIP1/MLKL pathway to induce necroptosis might be one of underlying mechanisms.

关键词

Keywords

references

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