title: Siamese crocodile bile induces apoptosis in NCI-H1299 human non-small cell lung cancer cells via a mitochondria-mediated intrinsic pathway and inhibits tumorigenesis.
abstract: Non-small-cell lung cancer (NSCLC) is a widespread and particularly aggressive form of cancer. Patients with NSCLC and early metastases typically have poor prognosis, highlighting the critical need for additional drugs to improve disease outcome following surgical resection. The present study aimed to determine if Siamese crocodile bile (SCB) had an anti‑cancer effect on NCI‑H1299 human NSCLC cells. The inhibitory mechanism of SCB was examined in cell culture and nude mice. In vitro experimental results revealed that SCB inhibited the proliferation and colony‑forming ability of NCI‑H1299 cells by arresting cell cycle and inducing apoptosis. The loss of the mitochondrial membrane potential and the release of cytochrome c indicated that SCB treatment may lead to mitochondrial dysfunction in NCI‑H1299 cells. At the molecular level, SCB altered the ratio of protein expression of Bax/Bcl‑2 and activated associated caspases, suggesting that intrinsic pathway involvement in the SCB‑induced apoptosis of NCI‑H1299 cells. In the in vivo experiments, intraperitoneal injection of SCB for 4 weeks inhibited xenograft tumor growth by 46.8% without observable toxicity in nude mice. Immunohistochemistry analysis of proliferating cell nuclear antigen and vascular endothelial growth factor also revealed that SCB inhibited cell proliferation and metastasis in NSCLC xenograft tumors. Overall, SCB exerted an anti-cancer effect on NCI‑H1299 human NSCLC cells in vitro and in vivo and may have therapeutic potential for the treatment of human NSCLC.
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Hua-Liang
authors.initials: HL
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Wei-Xi
authors.initials: WX
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Qing-Xi
authors.initials: QX
authors.lastname: Chen
authors.affiliation: Center Laboratory, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China.
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Shen
mesh_terms: D000489:Alligators and Crocodiles; D000818:Animals; D017209:Apoptosis; D001646:Bile / Q000737:chemistry*; D063646:Carcinogenesis / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism*; D015398:Signal Transduction; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays