title: Subamolide a induces mitotic catastrophe accompanied by apoptosis in human lung cancer cells.
abstract: This study investigated the anticancer effects of subamolide A (Sub-A), isolated from Cinnamomum subavenium, on human nonsmall cell lung cancer cell lines A549 and NCI-H460. Treatment of cancer cells with Sub-A resulted in decreased cell viability of both lung cancer cell lines. Sub-A induced lung cancer cell death by triggering mitotic catastrophe with apoptosis. It triggered oxidant stress, indicated by increased cellular reactive oxygen species (ROS) production and decreased glutathione level. The elevated ROS triggered the activation of ataxia-telangiectasia mutation (ATM), which further enhanced the ATF3 upregulation and subsequently enhanced p53 function by phosphorylation at Serine 15 and Serine 392. The antioxidant, EUK8, significantly decreased mitotic catastrophe by inhibiting ATM activation, ATF3 expression, and p53 phosphorylation. The reduction of ATM and ATF3 expression by shRNA decreased Sub-A-mediated p53 phosphorylation and mitotic catastrophe. Sub-A also caused a dramatic 70% reduction in tumor size in an animal model. Taken together, cell death of lung cancer cells in response to Sub-A is dependent on ROS generation, which triggers mitotic catastrophe followed by apoptosis. Therefore, Sub-A may be a novel anticancer agent for the treatment of nonsmall cell lung cancer.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan ; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 801, Taiwan.
authors.forename: Jen-Yu
authors.initials: JY
authors.lastname: Hung
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Wen
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Hsu
authors.forename: En-Shyh
authors.initials: ES
authors.lastname: Lin
authors.forename: Ming-Shyan
authors.initials: MS
authors.lastname: Huang
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Kuo