Wang Yingyi, Sun Zhao, Chen Shuchang, Jiao Yuchen, Bai Chunmei
Oncology Department of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, NO. 1, ShuaiFuYuan Hutong, Dongcheng District, Beijing, 100730, People's Republic of China.
Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing, 100021, People's Republic of China.
Tumour Biol. 2016 Mar;37(3):3727-38. doi: 10.1007/s13277-015-4181-9. Epub 2015 Oct 14.
Ajoene, a garlic-derived organosulfur compound, exerts anti-tumorigenic effect against various cancers. However, little is known about the biological effect of ajoene on lung adenocarcinoma, an aggressive malignancy with dismal prognosis. We investigated the biological effect of ajoene on lung adenocarcinoma and the underlying pathway. Lung adenocarcinoma cells A549, NCI-H1373, and NCI-H1395, along with the noncancerous lung bronchus cells BEAS-2B, were used. MTT test showed that ajoene (25 μM) reduces viability of lung adenocarcinoma cells but not the noncancerous BEAS-2B cells. Bromodeoxyuridine incorporation assay revealed that ajoene inhibits proliferation of lung adenocarcinoma cells. Treatment of lung adenocarcinoma cells with ajoene enhances apoptosis and ROS generation in a time- and dose-dependent fashion. Abrogation of caspase activation by zVAD-fmk completely prevents the ajoene-induced apoptosis; whereas block of ROS generation by N-acetylcysteine partly abolishes the ajoene-induced apoptosis. ROS-mediated induction of apoptosis contributes partially to the anti-tumorigenic property of ajoene observed, a phenomenon also confirmed by xenograft tumor study. Mitogen activated protein kinases (MAPKs), pivots of ROS-mediated signaling pathway, are activated upon ajoene treatment; Jun-N-terminal kinase (JNK)/p38 activations are required for signaling pathway underlying the ajoene-induced apoptosis. Our results suggest that ROS-mediated activation of JNK/p38 contributes partially to the pro-apoptotic action of ajoene on cells of lung adenocarcinoma. Ajoene may be a promising chemotherapeutic agent for lung adenocarcinoma.
阿霍烯是一种源自大蒜的有机硫化合物，对多种癌症具有抗肿瘤作用。然而，关于阿霍烯对肺腺癌（一种预后不佳的侵袭性恶性肿瘤）的生物学作用知之甚少。我们研究了阿霍烯对肺腺癌的生物学作用及其潜在途径。使用了肺腺癌细胞A549、NCI-H1373和NCI-H1395，以及非癌性肺支气管细胞BEAS-2B。MTT试验表明，阿霍烯（25μM）可降低肺腺癌细胞的活力，但对非癌性BEAS-2B细胞无影响。溴脱氧尿苷掺入试验显示，阿霍烯可抑制肺腺癌细胞的增殖。用阿霍烯处理肺腺癌细胞可增强细胞凋亡和活性氧（ROS）生成，且呈时间和剂量依赖性。zVAD-fmk消除半胱天冬酶激活可完全阻止阿霍烯诱导的细胞凋亡；而N-乙酰半胱氨酸阻断ROS生成可部分消除阿霍烯诱导的细胞凋亡。ROS介导的细胞凋亡诱导部分促成了所观察到的阿霍烯的抗肿瘤特性，异种移植肿瘤研究也证实了这一现象。丝裂原活化蛋白激酶（MAPKs）是ROS介导信号通路的枢纽，在阿霍烯处理后被激活；阿霍烯诱导细胞凋亡的信号通路需要Jun-N端激酶（JNK）/p38激活。我们的结果表明，ROS介导的JNK/p38激活部分促成了阿霍烯对肺腺癌细胞的促凋亡作用。阿霍烯可能是一种有前途的肺腺癌化疗药物。
