Betulinic Acid Extracted from Guava (Psidium guajava L.) Leaves Inhibits Human Cholangiocarcinoma Cell Metastasis by Activating E-cadherin and Inhibiting MMP-9 and VEGF.

BACKGROUND

Cholangiocarcinoma, a bile duct cancer, is highly metastatic. Betulinic acid (BA), a pentacyclic triterpene glycoside found in the leaves of guava (Psidium guajava L.), exhibits various biological activities, including inhibition of cancer progression in multiple cancer cell types. However, the mechanism of action of BA in human cholangiocarcinoma (HuCCA) invasion and metastasis remains unclear.

OBJECTIVE

This study investigated the effects of BA on HuCCA cell apoptosis, invasion, and metastasis.

METHODS

The effects of BA treatment on apoptosis, invasion, and metastasis were determined using immunofluorescence staining, transwell invasion assay, wound healing assays, and Western blot analysis, respectively.

RESULTS

The findings revealed that BA effectively reduced metastasis and invasion in HuCCA cells. Mechanistically, this effect was associated with an increase in E-cadherin expression and a corresponding downregulation of MMP-9 and VEGF. Furthermore, BA-induced apoptosis was correlated with an increase in caspase-3 activity.

CONCLUSION

These findings suggest that BA extract from guava leaves not only induces apoptosis but also actively counteracts invasion and metastasis by upregulating E-cadherin and suppressing the expression of MMP-9 and VEGF. Therefore, BA from guava leaves shows significant promise as a therapeutic agent against the development and metastasis of HuCCA.