Alpha-lipoic acid induced apoptosis of PC3 prostate cancer cells through an alteration on mitochondrial membrane depolarization and MMP-9 mRNA expression.

Abstract

Cancer has become an important cause of mortality and morbidity in the world. Over the past decades, biomedical research revealed insights into the molecular events and signaling pathways involved in carcinogenesis and cancer progression. Matrix metalloproteinases (MMPs) are a diverse family of enzymes that can degrade various components of the extracellular matrix and are considered as potential diagnostic and prognostic biomarkers for many cancer types and cancer stages. Recently, studies on the role of natural-origin active substances in the prevention of cancer development gained importance. Among them, the α-lipoic acid, which is commonly found in plants, displayed potent anti-proliferative effects on cancer cell lines. However, the effect of the compound on the induction of apoptosis and mRNA expression of MMPs in human prostate cancer cells remains unclear. The present study aimed to evaluate the anti-proliferative and apoptotic activity of α-lipoic acid in human PC3 prostate carcinoma cells considering different concentrations and exposure durations. The findings showed that, α-lipoic acid significantly decreased PC3 cell viability with an IC50 value of 1.71 mM at 48 h (p < 0.05). Additionally, the compound significantly increased Annexin-V binding in cells compared to control and induced a significant alteration in mitochondrial membrane potential and caspase levels (p < 0.05). Furhermore, the RT-PCR analyses have revealed that α-lipoic acid reduced MMP-9 mRNA expression in PC3 cells compared to the control (p < 0.05). In conclusion, this study highlights that α-lipoic acid induced apoptosis in human PC3 prostate cancer cells and inhibited the MMP-9 gene at the mRNA level, which is known to play a role in metastasis development.

• Authors: Aybuke Celik, Filiz Bakar-Ates
• Journal: Medical oncology (Northwood, London, England) (Med Oncol) Vol. 40 Issue 8 Pg. 244 (Jul 15 2023) ISSN: 1559-131X [Electronic] United States
• PMID: 37453954 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Thioctic Acid
• Matrix Metalloproteinase 9
• Matrix Metalloproteinases
• RNA, Messenger

Topics

• Male
• Humans
• Thioctic Acid (pharmacology)
• Matrix Metalloproteinase 9 (genetics)
• PC-3 Cells
• Mitochondrial Membranes (metabolism, pathology)
• Cell Line, Tumor
• Apoptosis
• Prostatic Neoplasms (drug therapy, genetics, metabolism)
• Matrix Metalloproteinases
• RNA, Messenger (genetics)