title: Punica granatum (pomegranate) leaves extract induces apoptosis through mitochondrial intrinsic pathway and inhibits migration and invasion in non-small cell lung cancer in vitro.
abstract: Most conventional treatments on non-small cell lung carcinoma always accompany with awful side effects, and the incidence and mortality rates of this cancer are increasing rapidly worldwide. The objective of this study was to examine the anticancer effects of extract of Punica granatum (pomegranate) leaves extract (PLE) on the non-small cell lung carcinoma cell line A549, H1299 and mouse Lewis lung carcinoma cell line LL/2 in vitro, and explore its mechanisms of action. Our results have shown that PLE inhibited cell proliferation in non-small cell lung carcinoma cell line in a concentration- and time-dependent manner. Flow cytometry (FCM) assay showed that PLE affected H1299 cell survival by arresting cell cycle progression in G2/M phase in a dose-dependent manner and inducing apoptosis. Moreover, PLE could also decrease the reactive oxygen species (ROS) and the mitochondrial membrane potential (ΔYm), indicating that PLE may induce apoptosis via mitochondria-mediated apoptotic pathway. Furthermore, PLE blocked H1299 cell migration and invasion, and the reduction of matrix metalloproteinase (MMP) MMP-2 and MMP-9 expression were also observed in vitro. These results suggested that PLE could be an effective and safe chemotherapeutic agent in non-small cell lung carcinoma treatment by inhibiting proliferation, inducing apoptosis, cell cycle arrest and impairing cell migration and invasion.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, West China Medical School, Sichuan University, 17# 3rd Section, Ren Min South Road, 610041 Chengdu, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, 17# 3rd Section, Ren Min South Road, 610041 Chengdu, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Food & Drugs Inspection & Testing Institute of Sichuan province, Chengdu, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, 17# 3rd Section, Ren Min South Road, 610041 Chengdu, China.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, West China Medical School, Sichuan University, 17# 3rd Section, Ren Min South Road, 610041 Chengdu, China.
authors.forename: Juanxiu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, West China Medical School, Sichuan University, 17# 3rd Section, Ren Min South Road, 610041 Chengdu, China.
authors.forename: Sisi
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, West China Medical School, Sichuan University, 17# 3rd Section, Ren Min South Road, 610041 Chengdu, China.
authors.forename: Yuanle
authors.initials: Y
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, 17# 3rd Section, Ren Min South Road, 610041 Chengdu, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, 17# 3rd Section, Ren Min South Road, 610041 Chengdu, China. Electronic address: yeth1309@scu.edu.cn.
authors.forename: Tinghong
authors.initials: T
authors.lastname: Ye
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, West China Medical School, Sichuan University, 17# 3rd Section, Ren Min South Road, 610041 Chengdu, China. Electronic address: yinwenya@scu.edu.cn.
authors.forename: Wenya
authors.initials: W
authors.lastname: Yin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004610:Ellagic Acid / Q000737:chemistry / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D047348:Hydrolyzable Tannins / Q000737:chemistry / Q000494:pharmacology; D016014:Linear Models; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D029561:Lythraceae / Q000737:chemistry*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014709:Vero Cells
chemical_list: D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D004610:Ellagic Acid; C115642:punicalagin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Apoptosis; Migration and invasion; Non-small cell lung carcinoma; P. granatum leaves extract (PLE); Reactive oxygen species