Background and Objective: Phenformin, and flavonoid compounds, quercetin and myricetin are effective against many types of cancers. This study evaluated the treatments of phenformin in combination with quercetin or myricetin in the inhibition of cholangiocarcinoma (CCA) cells.

Methods: Cholangiocarcinoma cells, KKU-156, were used in this study. Cell cytotoxicity was evaluated by sulforhodamine-B assay (SRB). Mitochondrial membrane potential (Dym) was analyzed by JC-1 assay.

Results: Phenformin significantly inhibited proliferation of cancer cells. Phenformin in combination with quercetin, but not myricetin, could increase the cytotoxicity of cancer cells. Phenformin, quercetin or in the combination induced the loss of mitochondrial transmembrane potential.

Conclusions: Quercetin increased phenformin in inhibition of cancer cell growth. The mechanism may be by the increase of induction of mitochondrial damage leading to cell death.  This finding suggests that phenformin in combination with quercetin has potential to increase efficacy of chemotherapy of cholangiocarcinoma.