Zheng Xi, Xu Ying, Liu Bei, Qi Yan, Zhang Ying, Li Xiaosi, Zhang Xia, Pu Xiaojia, Li Siwen, Chen Zhe, Wan Chunping
The No. 1 Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming 650021, China.
School of Pharmacy, Yunnan University of Traditional Chinese Medicine, Kunming 650500, China.
Evid Based Complement Alternat Med. 2019 Jun 9;2019:9076269. doi: 10.1155/2019/9076269. eCollection 2019.
L. (), as a traditional medicinal plant, is used as treatment for tumors in traditional Chinese and Indian medical practice. However, its underlying molecular mechanisms remain largely unresolved. The current study investigated its antitumor activity and the underlying molecular mechanisms. Cell viability was detected by a real-time cell analysis system and MTT assay. Antitumor effect of ethyl acetate extract of (EAAC) on NIC-H1975 tumors was assessed in BALB/c-nu/nu mouse. Apoptosis was measured using Hoechst33342 staining and Annexin V/PI-staining. Apoptosis-related proteins and MAPK signaling pathways were analyzed based on Western blot assay. EAAC exhibited the highest cytotoxic activity than other polar parts. Meanwhile, EAAC could inhibit sensitive cell line NIC-H1975 proliferation in a concentration-dependent and time-dependent manner. Furthermore, EAAC had a significant inhibitory effect on NIC-H1975 tumor growth in BALB/c-nu/nu mouse. NIC-H1975 cells showed obvious apoptosis characteristics after EAAC treatment. Fas, caspase family members caspase 3, caspase 9, and caspase 8 showed dose-dependent induction by EAAC treatment, with increasing PARP cleavage. Additionally, EAAC significantly downregulated antiapoptotic proteins Bcl-2, XIAP, survivin, and Mcl-1 and upregulated proapoptosis proteins Bak, Bax, as well as activation of p38 and JNK MAPK signaling pathways. Moreover, inhibiting p38 and JNK MAPK by pharmacological inhibitors abrogated EAAC-induced apoptosis. Our data indicated that EAAC exerted potent antitumor effect both and in by triggering the apoptotic pathway.
作为一种传统药用植物，在传统中医和印度医学实践中，L. () 被用于治疗肿瘤。然而，其潜在的分子机制在很大程度上仍未得到解决。当前的研究调查了其抗肿瘤活性及潜在的分子机制。通过实时细胞分析系统和MTT法检测细胞活力。在BALB/c-nu/nu小鼠中评估了L. () 的乙酸乙酯提取物（EAAC）对NIC-H1975肿瘤的抗肿瘤作用。使用Hoechst33342染色和Annexin V/PI染色检测细胞凋亡。基于蛋白质免疫印迹法分析凋亡相关蛋白和MAPK信号通路。EAAC表现出比其他极性部位更高的细胞毒性活性。同时，EAAC能够以浓度依赖性和时间依赖性方式抑制敏感细胞系NIC-H1975的增殖。此外，EAAC对BALB/c-nu/nu小鼠中的NIC-H1975肿瘤生长具有显著的抑制作用。EAAC处理后，NIC-H1975细胞表现出明显的凋亡特征。Fas、半胱天冬酶家族成员半胱天冬酶3、半胱天冬酶9和半胱天冬酶8在EAAC处理后呈剂量依赖性诱导，PARP裂解增加。此外，EAAC显著下调抗凋亡蛋白Bcl-2、XIAP、生存素和Mcl-1，并上调促凋亡蛋白Bak、Bax，以及激活p38和JNK MAPK信号通路。此外，通过药理学抑制剂抑制p38和JNK MAPK可消除EAAC诱导的细胞凋亡。我们的数据表明，EAAC通过触发凋亡途径在体外和体内均发挥了强大的抗肿瘤作用。
