The molecular mechanisms of Tanshinone IIA on the apoptosis and arrest of human esophageal carcinoma cells.
OBJECTIVE
To explore the possible mechanisms of Tanshinone IIA (TanIIA) on esophageal carcinoma cell lines.


METHODS
Two human esophageal carcinoma cell lines (EC-1 cells and ECa-109 cells) were treated with different concentrations of TanIIA. Cell proliferation was measured by CCK-8, colony-forming efficiency was calculated, cell cycle and apoptosis were measured, and changes in cell cycle- and apoptosis-related gene expression were measured by Western blotting.


RESULTS
The CCK-8 and colony formation assay indicated that TanIIA inhibited the cell proliferation of human esophageal cancer cells (IC50 below 1 μg/mL) at 48 h. Hoechst 33258 and flow cytometry showed that TanIIA induced apoptosis in both esophageal cancer cell lines. Flow cytometry showed that TanIIA arrested cell cycle in S phase and G2/M phase. Western blotting analysis showed that Akt1 and its phosphorylation were inhibited, the Bax/Bcl-2 ratio increased, and both caspase-9 and caspase-3 were activated after treatment with 1.3 μg/mL TanIIA at 48 h. Meanwhile, p53 and p21 protein levels increased, whereas cyclin B1, CDC2, and CDC2 phosphorylation were inhibited.


CONCLUSIONS
TanIIA inhibits the growth of esophageal cancer cells and induces apoptosis in a time-dependent and concentration-dependent manner, possibly by affecting cell cycle- and apoptosis-related signaling pathways.
Cancer Research Institute, Zhejiang Cancer Hospital, No. 38 Guangji Road, Hangzhou, Zhejiang 310022, China ; Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, Zhejiang 310022, China.
Jiang-Feng
JF
Wang
Cancer Research Institute, Zhejiang Cancer Hospital, No. 38 Guangji Road, Hangzhou, Zhejiang 310022, China ; Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, Zhejiang 310022, China.
Jian-Guo
JG
Feng
Cancer Research Institute, Zhejiang Cancer Hospital, No. 38 Guangji Road, Hangzhou, Zhejiang 310022, China ; Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, Zhejiang 310022, China.
Jing
J
Han
Cancer Research Institute, Zhejiang Cancer Hospital, No. 38 Guangji Road, Hangzhou, Zhejiang 310022, China ; Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, Zhejiang 310022, China.
Bei-Bei
BB
Zhang
Cancer Research Institute, Zhejiang Cancer Hospital, No. 38 Guangji Road, Hangzhou, Zhejiang 310022, China ; Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, Zhejiang 310022, China.
Wei-Min
WM
Mao
D045784:Abietanes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D009363:Neoplasm Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D045784:Abietanes; D009363:Neoplasm Proteins; C021751:tanshinone