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ROS-mediated activation of JNK/p38 contributes partially to the pro-apoptotic effect of ajoene on cells of lung adenocarcinoma.

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      Abstract

      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.

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      Affiliations
      [1 ] 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.
      [2 ] 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.
      [3 ] 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. baichunmei2001@163.com.
      Journal
      Tumour Biol.
      Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
      1423-0380
      1010-4283
      Mar 2016
      : 37
      : 3
      26468015
      10.1007/s13277-015-4181-9
      10.1007/s13277-015-4181-9

      ROS, Adenocarcinoma, Ajoene, Apoptosis, Lung, MAPKs

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