Cratoxylum formosumExtracts 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.

Cytotoxic and antimigratory effects of Cratoxy formosum extract against HepG2 liver cancer cells

“…The current results indicated that CF activates cancer cell death or inhibits cancer cell proliferation by increasing p21 protein expression and inhibiting cylin D1 protein expression. Similarly, CF extracts have been shown to induce cell cycle arrest in CCA cells at the G 2 /M phase, and downregulate cyclin A and CDC25A protein expression (19). These results indicate that CF exerts potent activity against human HepG2 cancer cells.…”

“…CF selectively increased HepG2 liver cancer cell death when compared with normal cells by inducing caspase 3, 8 and 9, decreasing the mitochondrial function and increasing apoptotic body formation (18). Consistent with the effects of CF on cholangiocarcinoma (CCA) cells, CF inhibited CCA cell proliferation, induced cell apoptosis, triggered cell cycle (19). Furthermore, CF suppressed nuclear factor-κB and signal transducer and activator of transcription 3 nuclear translocation and transcriptional activity, and inhibited cancer progression and metastasis (19).…”

“…Consistent with the effects of CF on cholangiocarcinoma (CCA) cells, CF inhibited CCA cell proliferation, induced cell apoptosis, triggered cell cycle (19). Furthermore, CF suppressed nuclear factor-κB and signal transducer and activator of transcription 3 nuclear translocation and transcriptional activity, and inhibited cancer progression and metastasis (19). Problems with increasing drug resistance and drug toxicity have stimulated investigation into novel anticancer compounds derived from natural sources, such as plants.…”

“…CF appeared to inhibit the growth of HepG2 cancer cells. Previous in vitro studies revealed that CF inhibits growth and induces apoptosis in numerous types of cancer cell, including liver (18), oral (24), bile duct (19) and cervical (25). Senggunprai et al (19) demonstrated that CF was potently cytotoxic against CCA KKU-M156 cells, induced cell apoptosis and inhibited colony formation.…”

“…CF leaf extract selectively inhibited human U937 leukemia cancer cells when compared with normal cells based on observations of DNA laddering and nuclear morphological changes (17). Nonpunya et al (18) and Senggunprai et al (19) showed that ethanolic CF leaf extracts inhibit cancer cell proliferation and induce apoptosis. CF selectively increased HepG2 liver cancer cell death when compared with normal cells by inducing caspase 3, 8 and 9, decreasing the mitochondrial function and increasing apoptotic body formation (18).…”