14-Thienyl methylene matrine (YYJ18), the derivative from matrine, induces apoptosis of human nasopharyngeal carcinoma cells by targeting MAPK and PI3K/Akt pathways in vitro.
OBJECTIVE
Nasopharyngeal carcinoma (NPC) is a distinctive type of head and neck cancer with the highest incidence in South China. Previous studies have proved that matrine, a main alkaloid isolated from Sophora flavescens Ait, has antitumor activity against NPC. However, the effect is not so pronounced and the underlying mechanism remains largely unclear. Here we investigated whether 14-thienyl methylene matrine (YYJ18) that was derived from matrine could exert more effective suppression activity on NPC, along with the underlying mechanism.


METHODS
NPC cell lines CNE1, CNE2 and HONE1 were treated with YYJ18. Cell proliferation and apoptosis were determined by MTT assay and flow cytometry. Activation of mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways were determined by Western blotting and quantitative RT-PCR.


RESULTS
YYJ18 remarkably inhibited proliferation and induced apoptosis of all three NPC cell lines in a dose-dependent manner, especially in CNE2 cells. Furthermore, YYJ18 treatment significantly suppressed phosphorylation of p38 in CNE2 cells, but upregulated phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) and Akt. Next, alterations in downstream signaling were found, including activation of BCL2-associated X protein (Bax), caspase-3 and inactivation of B-cell CLL/lymphoma 2 (Bcl-2).


CONCLUSIONS
We demonstrate the potent inhibitory effects of 14-thienyl methylene matrine on NPC cells for the first time, which could be mediated by modulation of MAPK and PI3K/Akt pathways.
Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P.R.China.
Mao
M
Xie
Xiang
X
Yi
Renjun
R
Wang
Lisheng
L
Wang
Guangyao
G
He
Meichan
M
Zhu
Chenglin
C
Qi
Yikang
Y
Liu
Yu
Y
Ye
Songhua
S
Tan
Anzhou
A
Tang
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015394:Molecular Structure; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D054837:Quinolizidines / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000093842:Matrines
D000970:Antineoplastic Agents; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D054837:Quinolizidines; D013876:Thiophenes; C000596768:14-thienyl methylene matrine; D000093842:Matrines