title: Oridonin promotes G2/M arrest in A549 cells by facilitating ATM activation.
abstract: Previous studies have demonstrated that oridonin, a tetracyclic diterpenoid compound extracted from Rabdosia rubescens, inhibits proliferation and induces apoptosis in several tumor cell lines. However, the mechanism by which oridonin inhibits the cell cycle remains poorly understood. In the present study, possible mechanisms by which oridonin affects cell cycle progression were explored in A549 lung cancer cells. Flow cytometry analysis indicated that oridonin inhibited the proliferation of A549 cells by inducing G2/M cell cycle arrest in a dose‑dependent manner. Western blot analysis revealed that in oridonin treated cells, phosphorylated (p‑)ATM serine/threonine kinase (S1981), p‑checkpoint kinase 2 (CHK2) (T68), p‑p53, and phosphorylated H2A histone family member X protein levels were visibly increased, indicating that oridonin promoted G2/M arrest in A549 cells through the ATM‑p53‑CHK2 pathway. This data suggests that oridonin promotes G2/M arrest in A549 cells by facilitating ATM activation, which is likely a common mechanism in other tumor cell types when using this drug for cancer treatment.
authors.affiliation: Department of Respiratory Medicine, Clinical College of Anhui Medical University Affiliated Shenzhen Second People's Hospital, Shenzhen, Guangdong 518035, P.R. China.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Gastrointestinal Surgery, Clinical College of Anhui Medical University Affiliated Shenzhen Second People's Hospital, Shenzhen, Guangdong 518035, P.R. China.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: School of Medicine, Tongji University, Shanghai 200092, P.R. China.
authors.forename: Yongzhao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Thoracic Surgery, Clinical College of Anhui Medical University Affiliated Shenzhen Second People's Hospital, Shenzhen, Guangdong 518035, P.R. China.
authors.forename: Da
authors.initials: D
authors.lastname: Yao
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Maoqing
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Gengyun
authors.initials: G
authors.lastname: Sun
mesh_terms: D000072283:A549 Cells; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D037602:Isodon / Q000737:chemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D045786:Diterpenes, Kaurane; C011959:oridonin; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins