Cratoxylum formosum Extracts Inhibit Growth and Metastasis of Cholangiocarcinoma Cells by Modulating the NF-κB and STAT3 Pathways

ABSTRACT

Cratoxylum formosum Dyer has been used in Southeast Asian countries both for food and folk medicine. In this study, the leaf extracts of C. formosum were evaluated for anticancer effects on human cholangiocarcinoma (CCA) KKU-M156 cells. The results showed that the plant extracts possessed potent cytotoxicity against CCA cells. The cytotoxic activity was associated with an induction of cell apoptosis. Moreover, the colony forming ability of CCA cells was also inhibited by C. formosum extracts. Consistent with growth inhibitory effects, the plant extracts induced cell cycle arrest at the G2/M phase and downregulated cyclin A and Cdc25A protein expression. The extracts potently suppressed the migration and invasion properties of CCA cells. The effects were associated with the suppression of NF-κB and STAT3 nuclear translocation and transcriptional activity, and downregulation of genes involving in cancer progression and metastasis. Furthermore, the possible bioactive compounds in the extracts were analyzed by HPLC. Taken together, the potent anticancer activity of C. formosum against CCA indicates the plant promising use for CCA prevention and therapy.

Acknowledgements

We would like to acknowledge Prof. Ross H Andrews, for editing the manuscript via Publication Clinic, Khon Kaen University, Thailand.

Funding

This work was supported by the Thailand Research Fund (TRG5780006), the grant from Khon Kaen University (571801) and the Office of the Higher Education Commission through the Health cluster (SHeP-GMS) of Khon Kaen University, Thailand (NRU582017).