title: Harmine induces apoptosis and inhibits tumor cell proliferation, migration and invasion through down-regulation of cyclooxygenase-2 expression in gastric cancer.
abstract: Cyclooxygenase-2 (COX-2) plays an important role in the carcinogenesis and progression of gastric cancer. Harmine is reported as a promising drug candidate for cancer therapy; however, effects and action mechanism of harmine on the human gastric cancer cells remain unclear. This study evaluated the anti-tumor effects of harmine on human gastric cancer both in vitro and in vivo. The cell proliferation was determined using MTT colorimetric assay. Apoptosis was measured by DAPI staining and flow cytometry analysis. The wound healing and transwell invasion assays were performed to evaluate the effects of harmine on the migration and invasion of gastric cancer cells. The expression of COX-2, proliferating cell nuclear antigen (PCNA), Bcl-2, Bax and matrix metalloproteinase-2 (MMP-2) was detected by Western blot analysis. Our results showed that harmine significantly inhibited cellular proliferation, migration, invasion and induced apoptosis in vitro, as well as inhibited tumor growth in vivo. In addition, harmine significantly inhibited the expression of COX-2, PCNA, Bcl-2 and MMP-2 as well as increased Bax expression in gastric cancer cells. These results collectively indicate that harmine induces apoptosis and inhibits proliferation, migration and invasion of human gastric cancer cells, which may be mediated by down-regulation of COX-2 expression.
authors.affiliation: Department of Geriatric Gastroenterology, the First Affiliated Hospital to Nanjing Medical University, Nanjing 210029, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Geriatric Gastroenterology, the First Affiliated Hospital to Nanjing Medical University, Nanjing 210029, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Respiratory Medicine, the Affiliated Nanjing Children Hospital to Nanjing Medical University, Nanjing 210029, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital to Nanjing Medical University, Nanjing 210029, PR China.
authors.forename: Huae
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Oncology, the First Affiliated Hospital to Nanjing Medical University, Nanjing 210029, PR China.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Geriatric Gastroenterology, the First Affiliated Hospital to Nanjing Medical University, Nanjing 210029, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Geriatric Gastroenterology, the First Affiliated Hospital to Nanjing Medical University, Nanjing 210029, PR China. Electronic address: lxl@njmu.edu.cn.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Geriatric Gastroenterology, the First Affiliated Hospital to Nanjing Medical University, Nanjing 210029, PR China. Electronic address: swh@njmu.edu.cn.
authors.forename: Weihao
authors.initials: W
authors.lastname: Sun
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015536:Down-Regulation; D005753:Gastric Mucosa / Q000378:metabolism; D006247:Harmine / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D032443:Peganum / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013270:Stomach / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D052246:Cyclooxygenase 2 Inhibitors; D010936:Plant Extracts; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D006247:Harmine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Apoptosis; Cyclooxygenase-2; Gastric cancer; Harmine alcaloid; Invasion; Proliferation