Anticancer effects of alpha-lipoic acid, a potent organosulfur compound by modulating matrix metalloproteinases and apoptotic markers in osteosarcoma MG-63 cells.

Abstract

Osteosarcoma (OS), an extremely aggressive form of bone tumor primarily affects young adults. Despite significant advancements in clinical trials, the ability of cancer cells to metastasize and resist apoptosis remains a major challenge. To address these issues, novel therapeutic interventions with high specificity for these processes are essential. Alpha-lipoic acid (ALA), an organosulfur compound derived from octanoic acid, possesses a range of pharmacological properties. This study hypothesizes that ALA would inhibit metastasis and induce cell apoptosis in OS. To evaluate the potential of ALA, its effects on the migration, metastasis, and cell cycle of MG-63 OS cells were assessed, along with its ability to trigger apoptosis. To these aims, MG-63 cells were exposed to varying concentrations of ALA, and cell viability was measured using the alamarBlue assay. The impact of ALA on cell cycle progression, apoptosis, migration, and metastasis was analyzed through flow cytometry, scratch assay, and gelatin zymography. After validating the expression of MMP2, MMP9, VEGF, VEGFR, BAX, BCL-2, and P53 by the GEO database, the expression levels of these genes were examined through quantitative PCR (qPCR). Eventually, molecular docking was employed to simulate the interactions between ALA and matrix metalloproteinase (MMPs). The results demonstrated that ALA significantly inhibited cell migration, induced cell cycle arrest, and promoted apoptosis by upregulating P53 and BAX expression while downregulating BCL-2 levels. Furthermore, ALA was found to suppress the activity and expression of MMP2 and MMP9 and reduce the expression of angiogenesis markers. Notably, ALA interacted directly with the active site of MMP2 and MMP9. These findings suggest that ALA has the potential to be a promising agent with anti-cancer effects on MG-63 cells, warranting further preclinical investigations.