Matrine-Induced Apoptosis of Human Nasopharyngeal Carcinoma Cells via In Vitro Vascular Endothelial Growth Factor-A/Extracellular Signal-Regulated Kinase1/2 Pathway Inactivation

M. Xie; G. He; R. Wang; S. Shi; J. Chen; Y. Ye; L. Xie; X. Yi; A. Tang

doi:10.1055/s-0034-1367077

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2014; 46(08): 556-560
DOI: 10.1055/s-0034-1367077

Endocrine Research

Matrine-Induced Apoptosis of Human Nasopharyngeal Carcinoma Cells via In Vitro Vascular Endothelial Growth Factor-A/Extracellular Signal-Regulated Kinase1/2 Pathway Inactivation

M. Xie

¹Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, P. R. China

,

G. He

¹Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, P. R. China

,

R. Wang

²Department of Otolaryngology-Head & Neck Surgery, First people’s Hospital of Yibin, Yibin, P. R. China

,

S. Shi

¹Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, P. R. China

,

J. Chen

³Department of Physiology, Guilin Medical University, Guilin, P. R. China

,

Y. Ye

⁴Department of Emergency, First Affiliated Hospital of Guangxi Medical University, Nanning, P. R. China

,

L. Xie

¹Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, P. R. China

,

X. Yi

¹Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, P. R. China

,

A. Tang

¹Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, P. R. China

› Author Affiliations

Abstract

Matrine, a main active extract from Sophora flavescens Ait, has been demonstrated to exert anticancer effects on various cancer cell lines, such as malignant melanoma, breast cancer, and lung cancer. However, it is currently unclear whether matrine could also elicit an inhibitory effect on growth of nasopharyngeal carcinoma (NPC), let alone the possible molecular mechanisms. Therefore, in a previous study, we investigated matrine-induced proliferation inhibition and apoptosis in NPC cells. It was shown that proliferation of human NPC cells (CNE1 and CNE2) was significantly diminished by matrine in a dose- and time-dependent manner, and apoptosis was induced in both 2 NPC cells, particularly in CNE2 cells. Moreover, the increased apoptosis rate in matrine-treated CNE2 cells confirmed the proapoptotic activity of matrine. We further found that matrine treatment dose- and time-dependently reduced the levels of vascular endothelial growth factor-A (VEGF-A), and inactivated extracellular signal-regulated kinase1/2 (ERK1/2), followed by increased expression of downstream target caspase-3. Overall, we conclude that matrine could induce apoptosis of human NPC cells via VEGF-A/ERK1/2 pathway, which supports the potential use of matrine in clinically treating NPC.

Key words

matrine - nasopharyngeal carcinoma - MAPK - VEGF-A - ERK1/2

Full Text

References

References
1 Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral oncology 2009; 45: 309-316
2 Brennan B. Nasopharyngeal carcinoma. Orphanet J Rare Dis 2006; 1: 23
3 Xu T, Tang J, Gu M, Liu L, Wei W, Yang H. Recurrent nasopharyngeal carcinoma: a clinical dilemma and challenge. Curr Oncol 2013; 20: e406-e419
4 Hsu WL, Pan WH, Chien YC, Yu KJ, Cheng YJ, Chen JY, Liu MY, Hsu MM, Lou PJ, Chen IH, Yang CS, Hildesheim A, Chen CJ. Lowered risk of nasopharyngeal carcinoma and intake of plant vitamin, fresh fish, green tea and coffee: a case-control study in Taiwan. PLoS One 2012; 7: e41779
5 Agulnik M, Epstein JB. Nasopharyngeal carcinoma. Current management, future directions and dental implications. Oral Oncol 2008; 44: 617-627
6 Huang TT, Liu FG, Wei CF, Lu CC, Lin HC, Ojcius DM, Lai HC. Activation of Multiple Apoptotic Pathways in Human Nasopharyngeal Carcinoma Cells by the Prenylated Isoflavone, Osajin. Plos One 2011; 6: e18308
7 Tian J, Duan YX, Bei CY, Chen J. Calycosin induces apoptosis by upregulation of RASD1 in human breast cancer cells MCF-7. Horm Metab Res 2013; 45: 593-598
8 Liu YH, Liu YF, Guo XX. Current studies on anti-endotoxic chemical components of traditional Chinese medicine in China. Acta Pharmacol Sin 2001; 22: 1071-1077
9 Zhang B, Liu ZY, Li YY, Luo Y, Liu ML, Dong HY, Liu Y, Zhao PT, Jin FG, Li ZC. Antiinflammatory effects of matrine in LPS-induced acute lung injury in mice. Eur J Pharm Sci 2011; 44: 573-579
10 Chen Y, Zhu J. Anti-HBV effect of individual traditional Chinese herbal medicine in vitro and in vivo: an analytic review. J Viral Hepat 2013; 20: 445-452
11 Gao HY, Li GY, Lou MM, Li XY, Wei XY, Wang JH. Hepatoprotective effect of Matrine salvianolic acid B salt on Carbon Tetrachloride-Induced Hepatic Fibrosis. J Inflam 2012; 9: 16
12 Li XL, Chu WM, Liu JL, Xue XR, Lu YJ, Shan HL, Yang BF, Yang BF. Antiarrhythmic properties of long-term treatment with matrine in arrhythmic rat induced by coronary ligation. Biol Pharm Bull 2009; 32: 1521-1526
13 Li T, Wong VK, Yi XQ, Wong YF, Zhou H, Liu L. Matrine Induces Cell Anergy in Human Jurkat T Cells through Modulation of Mitogen-Activated Protein Kinases and Nuclear Factor of Activated T-Cells Signaling with Concomitant Up-Regulation of Anergy-Associated Genes Expression. Biol Pharm Bull 2010; 33: 40-46
14 Zhang Y, Zhang H, Yu P, Liu Q, Liu K, Duan H, Luan G, Yagasaki K, Zhang G. Effects of matrine against the growth of human lung cancer and hepatoma cells as well as lung cancer cell migration. Cytotechnology 2009; 59: 191-200
15 Hu MJ, Zeng H, Wu YL, Zhang YP, Zhang S, Qiao MM, Fu H. Synergistic effects of matrine and 5-fluorouracil on tumor growth of the implanted gastric cancer in nude mice. Chin J Dig Dis 2005; 6: 68-71
16 Yu P, Liu Q, Yaqasaki K, Wu E, Zhang G. Matrine suppresses breast cancer cell proliferation and invasion via VEGF-Akt-NF-kappaB signaling. Cytotechnology 2009; 59: 219-229
17 Dai ZJ, Gao J, Ji ZZ, Wang XJ, Ren HT, Liu XX, Wu WY, Kang HF, Guan HT. Matrine induces apoptosis in gastric carcinoma cells via alteration of Fas/FasL and activation of caspase-3. J Ethnopharmacol 2009; 123: 91-96
18 Yu P, Liu Q, Liu K, Yagasaki K, Wu E, Zhang G. Matrine suppresses breast cancer cell proliferation and invasion via VEGF-Akt-NF-kappaB signaling. Cytotechnology 2009; 59: 219-229
19 Zhang P, Wang Z, Chong T, Ji Z. Matrine inhibits proliferation and induces apoptosis of the androgen independent prostate cancer cell line PC-3. Mol Med Rep 2012; 5: 783-787
20 Liu XY, Fang H, Yang ZG, Wang XY, Ruan LM, Fang DR, Ding YG, Wang YN, Zhang Y, Jiang XL, Chen HC. Matrine inhibits invasiveness and metastasis of human malignant melanoma cell line A375 in vitro. Int J Dermatol 2008; 47: 448-456
21 Liang CZ, Zhang JK, Shi Z, Liu B, Shen CQ, Tao HM. Matrine induces caspase-dependent apoptosis in human osteosarcoma cells in vitro and in vivo through the upregulation of Bax and Fas/FasL and downregulation of Bcl-2. Cancer Chemother Pharmacol 2012; 69: 317-331
22 Zhang S, Zhang Y, Zhuang Y, Wang J, Ye J, Zhang S, Wu J, Yu K, Han Y. Matrine induces apoptosis in human acute myeloid leukemia cells via the mitochondrial pathway and Akt inactivation. Plos One 2012; 7: e46853
23 Pan J, Kong L, Lin S, Chen G, Chen Q, Lu JJ. The clinical significance of coexpression of cyclooxygenases-2, vascular endothelial growth factors, and epidermal growth factor receptor in nasopharyngeal carcinoma. Laryngoscope 2008; 118: 1970-1975
24 Tian Y, Xie Q, Tian Y, Liu Y, Huang Z, Fan C, Hou B, Sun D, Yao K, Chen T. Radioactive (125)I Seed Inhibits the Cell Growth, Migration, and Invasion of Nasopharyngeal Carcinoma by Triggering DNA Damage and Inactivating VEGF-A/ERK Signaling. Plos One 2013; 8: e74038
25 Tulalamba W, Janvilisri T. Nasopharyngeal carcinoma signaling pathway: an update on molecular biomarkers. Int J Cell Biol 2012; 2012: 594681
26 Fan Y, Chen H, Qiao B, Luo L, Ma H, Li H, Jiang J, Niu D, Yin Z. Opposing effects of ERK and p38 MAP kinases on HeLa cell apoptosis induced by dipyrithione. Mol Cells 2007; 23: 30-38
27 Hanahan D, Weinberg RA. Hallmarks of cancer. The next generation. Cell 2011; 144: 646-674
28 Liu B, Peng XC, Zheng XL, Wang J, Qin YW. MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo. Lung Cancer 2009; 66: 169-175
29 Chen CH, Lai JM, Chou TY, Chen CY, Su LJ, Lee YC, Cheng TS, Hong YR, Chou CK, Whang-Peng J, Wu YC, Huang CY. VEGFA upregulates FLJ10540 and modulates migration and invasion of lung cancer via PI3K/AKT pathway. Plos One 2009; 4: e5052
30 Plati J, Bucur O, Khosravi-Far R. Apoptotic cell signaling in cancer progression and therapy. Integr Biol (Camb) 2011; 3: 279-296
31 Hensley P, Mishra M, Kyprianou N. Targeting caspases in cancer therapeutics. Biol Chem 2013; 394: 831-843