The antitumour effect of galangin and luteolin with doxorubicin on chemically induced hepatocellular carcinoma in rats

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.

Luteolin, a flavone ingredient: Anticancer mechanisms, combined medication strategy, pharmacokinetics, clinical trials, and pharmaceutical researches

“…Research manifested that the combination of lapatinib and luteolin may hinder HER2 + breast cancer by sharply augmenting the level of FOXO3a and NQO1, two pivotal factors related to chemosensitivity in HER2 + breast cancer (Zhang, Liu, et al, 2020). In another study on the anti‐HCC effect of luteolin combined with doxorubicin, the authors speculated that luteolin, with its ability to decrease the levels of serum α‐fetoprotein‐L3, glypican 3, and heat shock proteins, may be a meaningful option for clinical application in HCC chemotherapy (Atwa et al, 2021). In addition, the combined administration of luteolin and 5‐FU could also engender a synergistic therapeutic effect on solid Ehrlich carcinoma (SEC) by increasing the levels of p53, caspase‐3, and endowed a better therapeutic effect than the single administration (Soliman et al, 2019).…”

Advances in the Mechanism of Luteolin against Hepatocellular Carcinoma Based on Bioinformatics and Network Pharmacology

“…With the development of natural medicine, the research on luteolin has made a great breakthrough, and the clinical significance of luteolin has been confirmed by a lot of reliable data 89 . Sorafenib, a small-molecule multi-kinase inhibitor, has been approved by the US Food and Drug Administration as an oral drug for the treatment of hepatocellular carcinoma and renal cell carcinoma.…”