Teucrium persicum Methanolic Extract Alters Cellular Homeostasis and Regulates the Expression of MMP-2, MMP-9, TP53, and β-catenin Genes in PC-3 Cells

Document Type : Research Articles

Authors

Atiye Baghernezhad

Majid Tafrihi

Abasalt Hosseinzadeh Colagar

Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran

https://doi.org/10.22067/jcmr.2025.95810.1121

Abstract

Reactive oxygen species (ROS) are highly reactive molecules that play a key role in cellular physiology.in Teucrium persicum, an Iranian endemic plant native to the southern regions of Iran, particularly the Fars province. It has long been used in traditional medicine for the treatment of headaches, abdominal pain, diabetes, inflammation, and hyperlipidemia. Our previous findings demonstrated that treatment of PC-3 prostate cancer cells with T. persicum extract induces significant cytotoxicity and programmed cell death. In the present study, we aimed to further explore the effects of the methanolic extract of T. persicum on lactate dehydrogenase (LDH) activity, intracellular ROS species levels, mitochondrial membrane potential, and the expression of Matrix metalloproteinase-2 (MMP-2), Matrix metalloproteinase-9 (MMP-9), Tumor protein 53 (TP53), and β-catenin (CTNNB1) genes in PC-3 cells. For this purpose, PC-3 cells were treated with both sublethal concentrations and concentrations above the IC₅₀ value of the extract. The results revealed that T. persicum treatment caused marked mitochondrial membrane damage and increased LDH release. These effects were associated with decreased intracellular ROS levels and loss of mitochondrial membrane potential, which correlated with reduced cellular uptake of rhodamine 123 in a dose-dependent manner. Furthermore, gene expression analyses showed that exposure of PC-3 cells to the extract at the IC₅₀ concentration led to significant downregulation of MMP-2, MMP-9, and CTNNB1 genes, accompanied by upregulation of TP53. Collectively, these findings suggest that the methanolic extract of T. persicum can inhibit the proliferation and survival of PC-3 prostate cancer cells through multiple molecular pathways. Further comprehensive studies are warranted to elucidate the precise mechanisms underlying these anticancer effects.

Keywords

Teucrium persicum

PC-3 cells

ROS, Lactate dehydrogenase, Cell death, Invasion

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