Zhang Yong, Zhang Rui, Ni Huanjuan
Department of Respiratory Medicine, The Affiliated Hospital of Panzhihua University, Panzhihua, China.
Department of Respiratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Arch Med Sci. 2019 May 17;16(2):446-452. doi: 10.5114/aoms.2019.85152. eCollection 2020.
Eriodictyol is an important flavonoid and is commonly present across the plant kingdom. Flavonoids have been reported to show incredible pharmacological potential. However, the anticancer activity of the important flavonoid eriodictyol has not been well reported. In the present study we determined its anticancer potential against the human lung cancer cell line A549.
The initial cytotoxicity induced by eriodictyol was measured by MTT assay. Flow cytometry was used to study the effects of eriodictyol on apoptosis, cell cycle phase distribution and mitochondrial membrane potential loss. The comet assay was used to measure DNA damage induced by eriodictyol in cancer cells while the western blot assay indicated effects of the compound on Bax/Blc-2 and PI3K/AKT/m-TOR proteins.
The results showed that eriodictyol has an IC value of 50 μM against human lung cancer cells as compared to the IC of 95 µM against non-cancerous FR2 cells. The molecule exerted its anticancer activity through induction of apoptosis by regulating the Bcl-2/Bax signalling pathway. It caused cell cycle arrest of human lung cancer A549 cells at G2/M phase. Eriodictyol was also found to cause a reduction of the mitochondrial membrane potential in a dose-dependent manner. Additionally, eriodictyol effectively inhibited the mTOR/PI3K/Akt signalling pathway in a dose-dependent manner.
Based on the above findings, we conclude that eriodictyol exerts its anticancer activity through induction of mitochondrial apoptosis and G2/M cell cycle arrest and inhibition of the TOR/PI3K/Akt cascade, indicating that it may have potential as a lead compound in the treatment of lung cancer, provided further in depth studies are done.
圣草酚是一种重要的黄酮类化合物，广泛存在于植物界。据报道，黄酮类化合物具有惊人的药理潜力。然而，重要的黄酮类化合物圣草酚的抗癌活性尚未得到充分报道。在本研究中，我们测定了其对人肺癌细胞系A549的抗癌潜力。
采用MTT法测定圣草酚诱导的初始细胞毒性。流式细胞术用于研究圣草酚对细胞凋亡、细胞周期阶段分布和线粒体膜电位丧失的影响。彗星试验用于测定圣草酚在癌细胞中诱导的DNA损伤，而蛋白质免疫印迹试验则显示该化合物对Bax/Blc-2和PI3K/AKT/m-TOR蛋白的影响。
结果表明，圣草酚对人肺癌细胞的IC50值为50μM，而对非癌性FR2细胞的IC50值为95μM。该分子通过调节Bcl-2/Bax信号通路诱导细胞凋亡发挥其抗癌活性。它导致人肺癌A549细胞在G2/M期发生细胞周期阻滞。还发现圣草酚以剂量依赖性方式导致线粒体膜电位降低。此外，圣草酚以剂量依赖性方式有效抑制mTOR/PI3K/Akt信号通路。
基于上述发现，我们得出结论，圣草酚通过诱导线粒体凋亡和G2/M细胞周期阻滞以及抑制TOR/PI3K/Akt级联反应发挥其抗癌活性，表明它可能有潜力作为治疗肺癌的先导化合物，但需要进一步深入研究。
