Holothuria scabra Methanol Extract Induces Apoptosis Via Modulation of Bax/Bcl-2 in Breast Cancer Mice Model

Breast cancer is a major contributor to cancer-related deaths worldwide. In the search for novel therapeutic agents, Holothuria scabra, a natural product traditionally used in folk medicine, has shown promising efficacy due to its bioactive compounds, such as holothurins. The study aims to investigate the effects of Holothuria scabra methanol extract (HSE) on a breast cancer mice model, mainly focusing on apoptosis-related gene upregulation. In silico molecular docking revealed the potential of holothurin to interact with the proapoptotic Bax and antiapoptotic Bcl-2 receptors, thus indicating its effect on apoptosis pathway. The in vivo breast cancer mice model was established by exposing female C57BL/6 mice to 7,12-dimethylbenz[a]anthracene and high-fat diet. Those mice were then treated with varying doses of HSE [0.33, 0.66, and 0.99 g/kg body weight (BW)]. Reverse transcription PCR analysis revealed increased Bax gene expression and decreased Bcl-2 gene expression in mice administered 0.66 and 0.99 g/kg body weight of HSE. Nevertheless, these changes were not statistically significant (P > 0.05). The calculated Bax/Bcl-2 ratio indicated a shift towards apoptosis in higher HSE doses, thus supporting an enhanced susceptibility of breast cancer cells to apoptosis. HSE administration at 0.66 g/kg BW notably increased the Bax/Bcl-2 ratio by ~2.71-fold, while 0.99 g/kg BW HSE elevated the Bax/Bcl-2 ratio by 3.5-fold compared with the positive control group (breast cancer mice without treatment; ratio < 1.00). These findings implied that HSE could promote apoptosis in breast cancer mice model, thus providing a potential natural therapeutic agent.