当前位置： SCI文献检索 > Molecular Medicine Reports期刊下所有文献 > Saikosaponin D inhibits autophagosome‑lysosome fusion and induces autophagy‑independent apoptosis in MDA‑MB‑231 breast cancer cells.

Saikosaponin D inhibits autophagosome‑lysosome fusion and induces autophagy‑independent apoptosis in MDA‑MB‑231 breast cancer cells.

Abstract：

:The present study aimed to explore the effect of Saikosaponin D (SSD) and its underlying mechanism on apoptosis and autophagy in human breast cancer MDA‑MB‑231 cells. MTT assay, flow cytometry, western blotting and confocal fluorescence microscopy detection were employed. SSD, a kind of triterpenoid saponins extracted from Radix bupleuri, has been demonstrated to have the effects of anti‑inflammatory, antioxidative and anticancer effects and can regulate autophagy. The present study revealed that SSD induced apoptosis through the activation of the p38 mitogen‑activated protein kinase (MAPK) signaling pathway in human breast cancer MDA‑MB‑231 cells. The administration of SSD promoted the phosphorylation/activation of p38 MAPK in MDA‑MB‑231 cells, whereas pretreatment with SB203580, an effective p38 MAPK inhibitor, attenuated SSD‑mediated apoptosis, the cleavage of PARP and the activation of caspase‑3. In addition, SSD blocked autophagic degradation by inhibiting autolysosome formation, resulting in the accumulation of autophagosomes. Mechanistically, the results of the present study revealed that SSD inhibited the formation of autophagosomes by inhibiting autophagosome‑lysosome fusion, rather than by damaging lysosome function. Furthermore, blocking autophagy degradation was not associated with SSD‑mediated apoptosis. The genetic knockdown of autophagy‑related protein 5 markedly reduced SSD‑mediated LC3B‑II accumulation; however, it did not affect the SSD‑mediated phosphorylation/activation of p38, cleavage of PARP, activation of caspase‑3 or apoptosis. In conclusion, the findings of the present study suggest that SSD may induce apoptosis and block autophagic degradation, which provides further evidence of the association between the inhibition of autophagic degradation and cell death.

journal_name

Mol Med Rep

journal_title

Molecular medicine reports

authors

Fu R,Zhang L,Li Y,Li B,Ming Y,Li Z,Xing H,Chen J

doi

10.3892/mmr.2020.11155

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

1026-1034

issue

eissn

1791-2997

issn

1791-3004

journal_volume

pub_type

杂志文章

在线工具

Saikosaponin D inhibits autophagosome‑lysosome fusion and induces autophagy‑independent apoptosis in MDA‑MB‑231 breast cancer cells.