title: Dracorhodin perchlorate induces G1/G0phase arrest and mitochondria-mediated apoptosis in SK-MES-1 human lung squamous carcinoma cells.
abstract: Dracorhodin perchlorate (DP) has recently been revealed to induce apoptosis in various types of cancer. However, the antitumor potential and molecular mechanisms of DP in human lung cancer have not been previously reported. Therefore, the present study aimed to investigate the effects of DP on cell viability, the cell cycle and apoptosis, using an MTT assay, flow cytometry and western blot studies. DP was identified to induce cellular and DNA morphological changes, and decreased the viability of SK-MES-1 human lung squamous carcinoma cells. DP significantly inhibited the growth of SK-MES-1 cells by inducing apoptosis and G1/G0cell cycle arrest in a dose-dependent manner via activation of p53 (P<0.05). Furthermore, DP promoted the significant upregulation of B cell lymphoma-2 (Bcl-2)-activated X protein and significant downregulation of Bcl-2 (P<0.05), inducing dissipation of the mitochondrial membrane potential (MMP). In addition, caspase-3 was activated by DP via the cleavage of its substrate, proteolytic cleavage of poly(ADP-ribose) polymerase. DP also induced caspase-independent apoptosis by significantly increasing the protein expression of the apoptosis-inducing factor (P<0.05), which is localized in mitochondria under the physiological conditions and released into the cytoplasm when MMP is dissipated. Furthermore, the present study demonstrated that DP significantly increased the generation of reactive oxygen species (P<0.05). In conclusion, the current study revealed that DP is able to induce cell cycle arrest and apoptosis in SK-MES-1 cells via activation of the mitochondrial pathway, indicating that DP may be a potential leading compound for the development of future lung cancer therapeutic regimes.
authors.affiliation: Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Guangxin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Peiyan
authors.initials: P
authors.lastname: Hua
authors.affiliation: Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Ranji
authors.initials: R
authors.lastname: Cui
authors.affiliation: Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Xingyi
authors.initials: X
authors.lastname: Zhang
keywords: SK-MES-1 cells; apoptosis; dracorhodin perchlorate