title: Temozolomide-perillyl alcohol conjugate induced reactive oxygen species accumulation contributes to its cytotoxicity against non-small cell lung cancer.
abstract: Temozolomide-perillyl alcohol conjugate (TMZ - POH), a novel temozolomide analog, was reported to play a cytotoxic role in triple-negative breast cancer and TMZ-resistant gliomas. In a current study we had demonstrated how TMZ - POH also exhibited its cytotoxicity against non-small cell lung cancer (NSCLC), the most common type of lung cancer, as evidence from cell/tumor proliferation inhibition, G2/M arrest, DNA damage and mitochondrial apoptosis. Importantly, TMZ - POH's cytotoxicity is closely related to reactive oxygen species (ROS) accumulation because it can be reversed by two ROS scavengers, catalase (CAT) and N-acetyl-L-cysteine (NAC). TMZ - POH induces mitochondrial transmembrane potential (MTP) decrease and ROS accumulation, in turn activates mitogen-activated protein kinase (MAPKs) signaling and mitochondrial apoptosis, and then exerts its cytotoxicity, thus proposing TMZ - POH as a potential therapeutic candidate for NSCLC.
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, PR China.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Song
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, PR China.
authors.forename: Xingwu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Clinical Laboratory, Shandong Cancer Hospital and Institute, Jinan, Shandong, PR China.|School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medicine Science, Jinan, Shandong, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Departments of Neurological Surgery, and Pathology, University of Southern California, Los Angeles, California.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Departments of Neurological Surgery, and Pathology, University of Southern California, Los Angeles, California.
authors.forename: Weijun
authors.initials: W
authors.lastname: Wang
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, PR China.
authors.forename: Xianrang
authors.initials: X
authors.lastname: Song
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077204:Temozolomide
chemical_list: D039821:Monoterpenes; D017382:Reactive Oxygen Species; C032208:perillyl alcohol; D003606:Dacarbazine; D000077204:Temozolomide