Department of Pneumology, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi, China.
Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China.
J Biochem Mol Toxicol. 2022 Oct;36(10):e23157. doi: 10.1002/jbt.23157. Epub 2022 Jul 14.
Farrerol is an herbal compound extracted from rhododendron. Here, our study is to investigate biological effects of farrerol on lung adenocarcinoma (LAC) cells. Human LAC cell lines and xenograft mouse model were utilized to define the effects of farrerol on tumor growth. Our findings indicated that farrerol significantly reduced LAC cell viability as well as the colony-forming capacity. Flow cytometry analysis demonstrated that farrerol contributed to cell apoptosis and G0/G1 phase cell cycle arrest. Mechanistically, farrerol treatment upregulated proapoptotic molecules (Bak, Bid, cleaved caspase-3 and cleaved caspase-9) and senescence markers (p16 and p2), but downregulated antiapoptosis genes (Bcl-2 and Bcl-XL) and cell cycle-associated genes (CyclinD1 and CDK4); meanwhile, the phosphorylation of retinoblastoma (Rb) protein was attenuated upon pretreatment of LAC cells with farrerol in comparison to untreated control. Further studies indicated that farrerol elevated reactive oxygen species levels, activating mitochondrial apoptotic pathway and causing cell apoptosis. However, exposure to farrerol did not result in significant apoptosis in normal lung epithelial cells, suggesting a tumor-specific effect of farrerol on LAC cells. In animal model, farrerol showed a significant inhibitory effect on LAC xenograft tumor growth. And gene expressions in tumor tissues, as mentioned above, were in line with the in vitro results. Taken together, these results suggested that farrerol caused LAC cell apoptosis by activating mitochondrial apoptotic pathway, whereas farrerol treatment had no notable effect on normal lung epithelial cells. Farrerol might be an effective therapeutic drug for LAC.
法呢醇是从杜鹃属植物中提取的一种草药化合物。在这里，我们的研究旨在探讨法呢醇对肺腺癌（LAC）细胞的生物学影响。利用人 LAC 细胞系和异种移植小鼠模型来定义法呢醇对肿瘤生长的影响。我们的研究结果表明，法呢醇显著降低了 LAC 细胞的活力和集落形成能力。流式细胞术分析表明，法呢醇导致细胞凋亡和 G0/G1 期细胞周期停滞。在机制上，法呢醇处理上调了促凋亡分子（Bak、Bid、cleaved caspase-3 和 cleaved caspase-9）和衰老标记物（p16 和 p2），但下调了抗凋亡基因（Bcl-2 和 Bcl-XL）和细胞周期相关基因（CyclinD1 和 CDK4）；同时，与未经处理的对照组相比，LAC 细胞用法呢醇预处理后，视网膜母细胞瘤（Rb）蛋白的磷酸化减弱。进一步的研究表明，法呢醇增加了活性氧水平，激活了线粒体凋亡途径并导致细胞凋亡。然而，法呢醇暴露在正常肺上皮细胞中并没有导致明显的细胞凋亡，这表明法呢醇对 LAC 细胞具有肿瘤特异性作用。在动物模型中，法呢醇对 LAC 异种移植肿瘤生长表现出显著的抑制作用。如上所述，肿瘤组织中的基因表达与体外结果一致。总之，这些结果表明，法呢醇通过激活线粒体凋亡途径导致 LAC 细胞凋亡，而法呢醇治疗对正常肺上皮细胞没有明显影响。法呢醇可能是治疗 LAC 的有效药物。
