Atwa Gamal, Omran Gamal, Elbaky Atef Abd, Okda Tarek
Department of Biochemistry, Faculty of Pharmacy, Port-Said University, Port-Said, Egypt.
Department of Biochemistry, Faculty of Pharmacy, Damanhur University, Damanhur, Egypt.
Contemp Oncol (Pozn). 2021;25(3):174-184. doi: 10.5114/wo.2021.110048. Epub 2021 Oct 14.
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.
肝细胞癌(HCC)是一种高发病率和高死亡率的高度恶性肿瘤,仍然是全球癌症相关死亡的第二大原因。高良姜素是一种从蜂胶和高良姜根中提取的天然黄酮类化合物,具有抗肿瘤功效,这导致了对相关研究兴趣的增加。此外,高良姜素在几种人类恶性肿瘤中抑制细胞增殖并诱导细胞凋亡。另一方面,木犀草素是一种存在于多种可食用植物中的天然黄酮类化合物,它通过抑制细胞存活途径和激活凋亡来增强不同癌细胞的细胞毒性。此外,木犀草素可阻断抗凋亡Bcl-2家族成员的活性。本研究旨在评估高良姜素和木犀草素联合应用的抗肿瘤作用,以及高良姜素和木犀草素联合阿霉素(DOX)在化学诱导的HCC大鼠模型中的抗肿瘤作用。我们的分析表明,高良姜素、木犀草素和DOX联合治疗对HCC显示出最大的抗肿瘤活性,这通过HCC标志物水平的显著降低得以观察到,包括血清甲胎蛋白-L3以及磷脂酰肌醇蛋白聚糖3和热休克蛋白在肝组织中的表达。另一方面,caspase-3在肝组织中的表达显著增加。这些结果表明,高良姜素和木犀草素联合治疗是HCC化疗临床应用的一个有前景的候选方案,特别是与DOX联合使用时。