Anti-proliferation effects, efficacy of cyasterone in vitro and in vivo and its mechanism.
Cyasterone was demonstrated potential inhibition effect in mouse skin carcinoma cells in published report. However, the molecular mechanisms of the cyasterone on cells remain unknown. Herein, we investigated the effects of cyasterone-induced apoptosis in A549 and MGC823 cells in vitro. MTT assay showed that cyasterone caused a significantly decreasing of the proliferation of A549 and MGC823 cells in a time-and dose-dependent manner with IC50values of 38.50±3.73μg/mL on A549 cells and 32.96±1.24μg/mL on MGC823 cells at 48h, respectively. Hoechst staining and TUNEL staining results indicated the quintessential apoptosis features in immunofluorescence image. Apoptosis and cell cycle were determined by flow cytometry. Cyasterone treatment triggered inhibition of epidermal growth factor receptor- phosphatidylinositol 3 kinase/protein kinase B (EGFR-AKT) signaling pathways and activation of P38 pathways. Furthermore, cyasterone inhibited MGC823 cells xenografted tumor growth in vivo with few changes in body weights. In conclusion, our findings provide the evidence that cyasterone inhibits growth of A549 and MGC823 cells, via regulating EGFR signaling pathway. Our results indicated that cyasterone, a natural EGFR inhibitor, maybe a promising anti-cancer agent.
Department of Traditional Chinese Medicine, HuaDong Hospital, FuDan University School of Medicine, Shanghai, 200040, PR China. Electronic address: lxg1082@gmail.com.
XinGang
X
Lu
Department of Traditional Chinese Medicine, HuaDong Hospital, FuDan University School of Medicine, Shanghai, 200040, PR China.
HongFu
H
Qiu
Department of Oncology, BaoShan Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201999, PR China.
Liu
L
Yang
Department of Traditional Chinese Medicine, PuTuo Hospital of Traditional Chinese Medicine, Shanghai, 200063, PR China.
JieYing
J
Zhang
Department of Rehabilitation, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, PR China.
ShuJie
S
Ma
Department of Traditional Chinese Medicine, RuiJin Hospital, JiaoTong University School of Medicine, Shanghai, 200025, PR China, PR China.
Lan
L
Zhen
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D045325:HCT116 Cells; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013265:Stigmasterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; C002082:cyasterone; D013265:Stigmasterol; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; C506433:CASP9 protein, human; D053453:Caspase 9
Apoptosis; Cell cycle arrest; Cyasterone; EGFR signaling pathway