Sonia Narwal, Anumeha Vashist, Reetu Hooda, Kiran Siwach, Rohit Kaushik, Gulshan Rohilla, Nisha Khatri, Minakshi Vashist
These findings indicate that SAC exerts selective cytotoxic effects on uterine leiomyoma cells, likely through modulation of the expression of selected PI3K/AKT pathway-related genes, supporting its potential as a therapeutic agent for uterine leiomyoma.
BACKGROUND: Uterine leiomyomas (fibroids) are the third most common, hormone-dependent benign tumors characterized by abnormal cell proliferation and dysregulation of signalling pathways, particularly PI3K/AKT. S-Allylcysteine (SAC), a bioactive compound from aged garlic (Allium sativum), possesses anti-inflammatory and anticancer properties, but its effects on leiomyoma cells remain poorly understood.
AIM: This study aimed to evaluate the cytotoxic effects of SAC on primary uterine leiomyoma culture cells and its molecular influence on PI3K/AKT pathway-related gene expression.
METHODS: A total of 25 uterine leiomyoma and 10 adjacent apparently normal myometrium paired tissues were collected from women with uterine leiomyoma. Of the 25 patients included for primary cell culture study, paired leiomyoma and adjacent myometrial tissues were obtained from 10 patients, while leiomyoma tissues alone were obtained from the remaining 15 patients. Primary uterine leiomyoma and adjacent myometrial cells were cultured in DMEM/F12 medium and treated with SAC (12.5-400 µg/ml) for 48 h. Cell viability was assessed by MTT assay, morphological changes were examined microscopically, and expression of PI3K (specifically PIK3R1), AKT3, MTOR, and PTEN was analysed by RT-qPCR using GAPDH as the housekeeping gene. Relative expression was calculated by the ΔΔCt method. Statistical analysis was performed using a one-way repeated-measures ANOVA test.
RESULTS: SAC significantly reduced ULPC viability in a dose-dependent manner, with an IC₅₀ of 255.71 ± 17.12 µg/ml (p < 0.05). Treated cells showed apoptotic features, including cell rounding, shrinkage, and reduced confluency. UMPC cells exhibited lower sensitivity, indicating a differential cytotoxicity response. SAC significantly downregulated transcript levels of PI3K, AKT3, and MTOR, while upregulating PTEN (p < 0.05).
CONCLUSION: These findings indicate that SAC exerts selective cytotoxic effects on uterine leiomyoma cells, likely through modulation of the expression of selected PI3K/AKT pathway-related genes, supporting its potential as a therapeutic agent for uterine leiomyoma.