Abstract
Hepatocellular carcinoma (HCC), a highly malignant tumour with very high morbidity and mortality, remains the second cause of cancer-related deaths worldwide. Galangin is a naturally occurring flavonoid extracted from the propolis and root of Alpinia officinarum, which possesses antitumour efficacy, which has resulted in an increase in interest in related research. Additionally, galangin inhibits cell proliferation and induces apoptosis in several human malignancies. On the other hand, luteolin, a naturally occurring flavonoid found in a variety of edible plants, augments cytotoxicity in different cancer cells through the inhibition of cell-survival pathways and activation of apoptosis. Moreover, luteolin blocks the activity of anti-apoptotic Bcl-2 family members. The present study aimed to assess the antitumour effect of galangin and luteolin in combination and the antitumour effect of a combination of galangin and luteolin together with doxorubicin (DOX) in a chemically induced HCC rat model. Our analyses demonstrated that the combination treatment with galangin, luteolin, and DOX showed the greatest antineoplastic activity against HCC, which was observed by significant decreases in the levels of HCC markers, including serum α-fetoprotein-L3, and hepatic tissue expression of both glypican 3 and heat shock proteins. On the other hand, the hepatic tissue expression of caspase-3 was significantly increased. These results suggest that combination treatment with galangin and luteolin is a promising candidate for clinical use in HCC chemotherapy, especially when used in combination with DOX.