Cucurbitacin B inhibits growth and induces apoptosis through the JAK2/STAT3 and MAPK pathways in SH‑SY5Y human neuroblastoma cells.
Cucurbitacin B (CuB) is a tetracyclic triterpene that is contained in extracts from cucurbitaceous plants and has been demonstrated to have anticancer and anti‑inﬂammatory activities. The purpose of the present study was to determine whether CuB exhibits anticancer effects on SH‑SY5Y human neuroblastoma cells and to analyze the underlying molecular mechanism. The results demonstrated that CuB not only induced cell cycle arrest at the G2/M phase, but also induced apoptosis as characterized by positive Annexin V staining, downregulation of phospho‑Janus kinase 2 (p‑JAK2), phospho‑signal transducer and activator of transcription 3 (p‑STAT3), phospho‑extracellular signal‑regulated kinases and the activation of c‑Jun N‑terminal kinase and p38 mitogen activated protein kinase (MAPK). CuB also altered the expression of gene products that mediated cell proliferation (Cyclin B1 and cyclin‑dependent kinase 1), cell survival (B‑cell lymphoma 2, Bcl2‑associated X protein) and increased the expression of p53 and p21. These results provide the evidence that JAK2/STAT3 and MAPKs have crucial roles in CuB‑induced growth inhibition and apoptosis in SH‑SY5Y human neuroblastoma cells.
The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Key Laboratory of Molecular Biophysics of Chinese Ministry of Education, College of Life Science and Technology, Huazhong University of Science & Technology (HUST), Wuhan, Hubei 430074, P.R. China.
Qian
Q
Zheng
The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Key Laboratory of Molecular Biophysics of Chinese Ministry of Education, College of Life Science and Technology, Huazhong University of Science & Technology (HUST), Wuhan, Hubei 430074, P.R. China.
Yunyi
Y
Liu
The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Key Laboratory of Molecular Biophysics of Chinese Ministry of Education, College of Life Science and Technology, Huazhong University of Science & Technology (HUST), Wuhan, Hubei 430074, P.R. China.
Weiwei
W
Liu
The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Key Laboratory of Molecular Biophysics of Chinese Ministry of Education, College of Life Science and Technology, Huazhong University of Science & Technology (HUST), Wuhan, Hubei 430074, P.R. China.
Fengyun
F
Ma
The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Key Laboratory of Molecular Biophysics of Chinese Ministry of Education, College of Life Science and Technology, Huazhong University of Science & Technology (HUST), Wuhan, Hubei 430074, P.R. China.
Yi
Y
Zhou
The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Key Laboratory of Molecular Biophysics of Chinese Ministry of Education, College of Life Science and Technology, Huazhong University of Science & Technology (HUST), Wuhan, Hubei 430074, P.R. China.
Mingjie
M
Chen
The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Key Laboratory of Molecular Biophysics of Chinese Ministry of Education, College of Life Science and Technology, Huazhong University of Science & Technology (HUST), Wuhan, Hubei 430074, P.R. China.
Junli
J
Chang
The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Key Laboratory of Molecular Biophysics of Chinese Ministry of Education, College of Life Science and Technology, Huazhong University of Science & Technology (HUST), Wuhan, Hubei 430074, P.R. China.
Yuesheng
Y
Wang
The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Key Laboratory of Molecular Biophysics of Chinese Ministry of Education, College of Life Science and Technology, Huazhong University of Science & Technology (HUST), Wuhan, Hubei 430074, P.R. China.
Guangxiao
G
Yang
The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Key Laboratory of Molecular Biophysics of Chinese Ministry of Education, College of Life Science and Technology, Huazhong University of Science & Technology (HUST), Wuhan, Hubei 430074, P.R. China.
Guangyuan
G
He
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D014315:Triterpenes; D051028:bcl-2-Associated X Protein; C041246:cucurbitacin B; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D048049:Extracellular Signal-Regulated MAP Kinases