Holothuria scabra methanol extract inhibits cancer growth through tgf-β/pi3k/pten signaling pathway in breast cancer mice model.

BACKGROUND:Molecules and cytokines can be targeted in cancer therapy. Transforming growth factor-beta (TGF-β) is a cytokine that acts on protein kinase receptors in the plasma membrane. The signaling pathway of TGF-β can trigger the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway, a signal transduction pathway important in cancer growth and development. However, this PI3K/AKT cascade can be inhibited by phosphatase and tensin homolog (PTEN) tumor suppressor genes. AIM:To determine the inhibitory effect of Holothuria scabra methanol extract (HSE) on breast cancer growth through the TGF-β/PI3K pathways and PTEN tumor suppressor gene on a breast cancer (BC) mice model. MATERIALS AND METHODS:Female C57BL6 mice were subcutaneously injected with carcinogen DMBA 1 mg/kg body weight (BW) and fed a high-fat diet (HFD). Mice were randomly divided into five groups (n = 6): negative control (NC) administered with a standard diet, positive control (PC) administered with DMBA and HFD, and three treatment groups (T1, T2, and T3) treated with HSE doses of 0.33, 0.66, and 0.99 g/kg BW for 12 weeks. TGF-β concentration in the blood serum of mice was assessed by ELISA and the PIK3CA and PTEN gene expression by qRT-PCR. RESULTS:The treatment with HSE resulted in a significant decrease in TGF-β concentrations in the blood sera of treatment groups T1 (35.31 ± 17.33), T2 (43.31 ± 17.42), and T3 (48.67 ± 20.94) pg/mL compared to the PC group (162.09 ± 11.60) pg/mL (p < 0.001). However, only HSE at a dose of 0.99 g/kg BW decreased the PIK3CA gene expression (p = 0.026), and at a dose of 0.66 g/kg BW increased the PTEN expression up to 4.93-fold. CONCLUSION:HSE is capable of inhibiting the TGF-β/PIK3CA pathway and increasing the PTEN gene expression.