Multi-omics profiling of PC-3 cells reveals bufadienolides-induced lipid metabolic remodeling by regulating long-chain lipids synthesis and hydrolysis.

Abstract

INTRODUCTION:

Lipid metabolism participates in various biological processes such as proliferation, apoptosis, migration, invasion, and maintenance of membrane homeostasis of prostate tumor cells. Bufadienolides, the active ingredients of Chansu, show a robust anti-proliferative effect against prostate cancer cells in vitro, but whether bufadienolides could regulate the lipid metabolism in prostate cancer has not been evaluated.

OBJECTIVES:

Our study explored the regulatory effects of bufadienolides on lipid metabolism in human prostate carcinoma cells (PC-3).

METHODS:

Untargeted lipidomics and transcriptomics were combined to study the effect of different bufadienolides interventions on lipid and gene changes of PC-3 cells. The key genes related to lipid metabolism and prostate cancer development were verified by qPCR and western blotting.

RESULTS:

Lipidomic analysis showed that the active bufadienolides significantly downregulated the content of long-chain lipids of PC-3 cells. Based on transcriptomic and qPCR analyses, many genes related to lipid metabolism were significantly regulated by active bufadienolides, such as ELOVL6, CYP2E1, GAL3ST1, CERS1, PLA2G10, PLD1, SPTLC3, and GPX2. Bioinformatics analysis of the Cancer Genome Atlas database and literature retrieval showed that elongation of very long-chain fatty acids protein 6 (ELOVL6) and phospholipase D1 (PLD1) might be important regulatory genes. Western blot analysis revealed that active bufadienolides could downregulate PLD1 protein levels which might promote anti-prostate cancer effect.

CONCLUSIONS:

All these findings support that bufadienolides might induce lipid metabolic remodeling by regulating long-chain lipids synthesis and phospholipid hydrolysis to achieve an anti-prostate cancer effect, and PLD1 would probably be the key protein.

• Authors: Rong Zhang, Zijia Zhang, Wenyong Wu, Jingying Shi, Entezar Berk, Wei Li, Yanping Deng, Zhaojun Wang, Jinjun Hou, Huali Long, Min Lei, Wanying Wu
• Journal: Metabolomics : Official journal of the Metabolomic Society (Metabolomics) Vol. 19 Issue 2 Pg. 6 (01 16 2023) ISSN: 1573-3890 [Electronic] United States
• PMID: 36645548 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Phospholipids
• Bufanolides

Topics

• Male
• Humans
• PC-3 Cells
• Hydrolysis
• Multiomics
• Metabolomics
• Phospholipids (metabolism)
• Prostatic Neoplasms (metabolism)
• Bufanolides