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Fungal metabolite altersolanol a exhibits potent cytotoxicity against human placental trophoblasts in vitro via mitochondria-mediated apoptosis.

Fungal metabolite altersolanol a exhibits potent cytotoxicity against human placental trophoblasts in vitro via mitochondria-mediated apoptosis.

Authors :
Gu, Ting
Wen, Yuting
Zhou, Qian
Yuan, Wei
Guo, Haichun
Chang, Wen-Lin
Yang, Qing
Source :
Mycotoxin Research; Aug2024, Vol. 40 Issue 3, p419-432, 14p
Publication Year :
2024

Abstract

Altersolanol A, a fungus-derived tetrahydroanthraquinone, has shown cytotoxic effects on multiple cancer cells. However, its reproductive toxicity in humans has not been well-addressed. The present study was aimed at investigating the cytotoxicity of altersolanol A on human placental trophoblasts including choriocarcinoma cell line JEG-3 and normal trophoblast cell line HTR-8/SVneo in vitro. The results showed that altersolanol A inhibited proliferation and colony formation of human trophoblasts, and the choriocarcinoma cells were more sensitive to the compound than the normal trophoblasts. Altersolanol A induced cell cycle arrest at G2/M phase in JEG-3 cells and S phase in HTR-8/SVneo cells, downregulated the expression of cell cycle-related checkpoint proteins, and upregulated the p21 level. Altersolanol A also promoted apoptosis in human trophoblasts via elevating the Bax/Bcl-2 ratio and decreasing both caspase-3 and caspase-9 levels. Meanwhile, altersolanol A suppressed the mitochondrial membrane potential and induced ROS production and cytochrome c release, which activated the mitochondria-mediated intrinsic apoptosis. Moreover, migration and invasion were inhibited upon altersolanol A exposure with downregulation of matrix metalloproteinase (MMP)-2 in JEG-3 cells and MMP-9 in HTR-8/SVneo cells. Mechanically, altersolanol A supplement decreased the phosphorylation of JNK, ERK, and p38, manifesting the inactivation of MAPK signaling pathway in the human trophoblasts. In conclusion, altersolanol A exhibited potential reproductive cytotoxicity against human trophoblasts via promoting mitochondrial-mediated apoptosis and inhibiting the MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01787888
Volume :
40
Issue :
3
Database :
Complementary Index
Journal :
Mycotoxin Research
Publication Type :
Academic Journal
Accession number :
178528239
Full Text :
https://doi.org/10.1007/s12550-024-00539-0