Vitamin C enhances anticancer activity in methotrexate-treated Hep3B hepatocellular carcinoma cells

被引:32
作者
Yiang, Giou-Teng [1 ,2 ]
Chou, Pei-Lun [3 ,4 ]
Hung, Yu-Ting [5 ]
Chen, Jen-Ni [6 ]
Chang, Wei-Jung [7 ,8 ]
Yu, Yung-Luen [7 ,8 ,9 ]
Wei, Chyou-Wei [5 ]
机构
[1] Buddhist Tzu Chi Med Fdn, Taipei Tzu Chi Hosp, Dept Emergency Med, New Taipei 231, Taiwan
[2] Tzu Chi Univ, Sch Med, Dept Emergency Med, Hualien 970, Taiwan
[3] St Marys Hosp Luodong, Dept Internal Med, Div Allergy Immunol Rheumatol, Yilan 265, Taiwan
[4] Taipei Med Univ, Coll Med, Sch Med, Dept Internal Med, Taipei 110, Taiwan
[5] Hungkuang Univ, Master Program Biomed Nutr, Dept Nutr, Taichung 433, Taiwan
[6] Natl Chung Hsing Univ, Dept Food Sci & Biotechnol, Taichung 402, Taiwan
[7] China Med Univ, Grad Inst Canc Biol, Taichung 404, Taiwan
[8] China Med Univ, Ctr Mol Med, Taichung 404, Taiwan
[9] Asia Univ, Dept Biotechnol, Taichung 413, Taiwan
关键词
methotrexate; vitamin C; apoptosis; hepatocellular carcinoma; GREEN TEA EXTRACT; RANA-CATESBEIANA RIBONUCLEASE; INDUCED OXIDATIVE STRESS; BREAST-CANCER CELLS; ASCORBIC-ACID; N-ACETYLCYSTEINE; DOWN-REGULATION; INDUCED APOPTOSIS; HEPATOMA-CELLS; COMBINATION THERAPY;
D O I
10.3892/or.2014.3289
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Methotrexate (MTX) has been widely used for rheumatoid arthritis therapy for a long time. MTX is also used as an anticancer drug for various tumors. However, many studies have shown that high-dose MTX treatment for cancer therapy may cause liver and renal damage. Alhough the mechanisms involved in MTX-induced liver and renal damage require further research, many studies have indicated that MTX-induced cytotoxicity is associated with increases in oxidative stress and caspase activation. In order to reduce MTX-induced side-effects and increase anticancer efficiency, currently, combination treatments of low-dose MTX and other anticancer drugs are considered and applied for various tumor treatments. The present study showed that MTX induces increases in H2O2 levels and caspase-9/-3 activation leading to cell death in hepatocellular carcinoma Hep3B cells. Importantly, this study is the first to demonstrate that vitamin C can efficiently aid low-dose MTX in inducing cell death in Hep3B cells. Therefore, the present study provides a possible powerful therapeutic method for tumors using a combined treatment of vitamin C and low-dose MTX.
引用
收藏
页码:1057 / 1063
页数:7
相关论文
共 72 条
[1]   CONTROLLED SYNTHESIS OF HBSAG IN A DIFFERENTIATED HUMAN-LIVER CARCINOMA-DERIVED CELL-LINE [J].
ADEN, DP ;
FOGEL, A ;
PLOTKIN, S ;
DAMJANOV, I ;
KNOWLES, BB .
NATURE, 1979, 282 (5739) :615-616
[2]   Induction of Cell Death in Renal Cell Carcinoma With Combination of D-Fraction and Vitamin C [J].
Alexander, Bobby ;
Fishman, Andrew I. ;
Eshghi, Majid ;
Choudhury, Muhammad ;
Konno, Sensuke .
INTEGRATIVE CANCER THERAPIES, 2013, 12 (05) :442-448
[3]   Caspase-8 cleaves its substrates from the plasma membrane upon CD95-induced apoptosis [J].
Beaudouin, J. ;
Liesche, C. ;
Aschenbrenner, S. ;
Hoerner, M. ;
Eils, R. .
CELL DEATH AND DIFFERENTIATION, 2013, 20 (04) :599-610
[4]  
Çaglar Y, 2013, HISTOL HISTOPATHOL, V28, P865, DOI 10.14670/HH-28.865
[5]   Caffeic acid phenethyl ester (CAPE) prevents methotrexate-induced hepatorenal oxidative injury in rats [J].
Cakir, Tugrul ;
Ozkan, Erkan ;
Dulundu, Ender ;
Topaloglu, Umit ;
Sehirli, Ahmet Ozer ;
Ercan, Feriha ;
Sener, Emre ;
Sener, Goksel .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 2011, 63 (12) :1566-1571
[6]   The effects of n-acetylcysteine on methotrexate-induced oxidative renal damage in rats [J].
Cetinkaya, Ali ;
Kurutas, Ergul Belge ;
Bulbuloglu, Ertan ;
Kantarceken, Bulent .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2007, 22 (01) :284-285
[7]  
Cetinkaya A, 2006, MED SCI MONITOR, V12, pBR274
[8]   Downregulation of xIAP expression by small interfering RNA inhibits cellular viability and increases chemosensitivity to methotrexate in human hepatoma cell line HepG2 [J].
Chen, Jun ;
Xiao, Xin-Qiang ;
Deng, Chun-Ming ;
Su, Xian-Shi ;
Li, Gui-Yuan .
JOURNAL OF CHEMOTHERAPY, 2006, 18 (05) :525-531
[9]   Depression by a Green Tea Extract of Alcohol-Induced Oxidative Stress and Lipogenesis in Rat Liver [J].
Chen, Kuo-Hsin ;
Li, Ping-Chia ;
Lin, Wei-Hsiang ;
Chien, Chiang-Ting ;
Low, Boon-Hua .
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 2011, 75 (09) :1668-1676
[10]   Methotrexate induces apoptosis of human choriocarcinoma cell line JAR via a mitochondrial pathway [J].
Chen, Ya-Xia ;
Lv, Wei-Guo ;
Chen, Huai-Zeng ;
Ye, Feng ;
Xie, Xing .
EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY, 2009, 143 (02) :107-111