Progesterone augments epirubicin-induced apoptosis in HA22T/VGH cells by increasing oxidative stress and upregulating Fas/FasL

被引:20
作者
Chang, Wen-Tsan [1 ,2 ,3 ]
Hsieh, Bau-Shan [4 ]
Cheng, Hsiao-Ling [4 ]
Lee, King-Teh [1 ,2 ,3 ]
Chang, Kee-Lung [1 ,3 ,4 ]
机构
[1] Kaohsiung Med Univ Hosp, Coll Med, Grad Inst Med, Kaohsiung, Taiwan
[2] Kaohsiung Med Univ Hosp, Dept Surg, Div Hepatobiliary & Pancreat Surg, Kaohsiung, Taiwan
[3] Kaohsiung Med Univ, Coll Med, Sch Med, Kaohsiung 80708, Taiwan
[4] Kaohsiung Med Univ, Coll Med, Sch Med, Dept Biochem, Kaohsiung 80708, Taiwan
关键词
Hepatocellular carcinoma; Progesterone; Epirubicin; Apoptosis; Oxidative stress; HA22T/VGH cells; ADVANCED HEPATOCELLULAR-CARCINOMA; RANDOMIZED PHASE-III; REACTIVE OXYGEN; IN-VITRO; MEDROXYPROGESTERONE ACETATE; NEUROBLASTOMA-CELLS; HEPG2; CELLS; CANCER; CHEMOTHERAPY; DOXORUBICIN;
D O I
10.1016/j.jss.2014.01.063
中图分类号
R61 [外科手术学];
学科分类号
100210 [外科学];
摘要
Background: Although epirubicin, an anthracycline drug, is widely used to treat hepatocellular carcinoma, its therapeutic efficacy is disappointing. Thus, the efficacy of epirubicin may be improved when combined with other drugs. This study investigated the therapeutic potential of combination of progesterone and epirubicin in the treatment of the human hepatoma cell line HA22T/VGH and the possible mechanisms through which this combination might induce apoptosis. Materials and methods: HA22T/VGH cells were treated without or with 25 mu M progesterone and/or 0.5 mu M epirubicin and analyzed for oxidative stress, redox status, Fas/FasL expression, caspase activity, and apoptosis. Results: HA22T/VGH cells treated with epirubicin increased the production of reactive oxygen species and nitric oxide, the expression of Fas, FasL, and Fas-associated death domain, and the activities of caspase-8 and caspase-3. Epirubicin treatment also decreased glutathione resulting in the induction of apoptosis. Treatment with progesterone alone increased nitric oxide production, but it did not affect the other parameters. However, when HA22T/VGH cells were treated with progesterone and epirubicin, the effects of epirubicin were enhanced. Conclusions: Our observations suggest that progesterone enhances the efficacy of epirubicin. The increased efficacy is potentially attributed to progesterone's enhancement of epirubicin-induced oxidative stress, thereby reducing redox status. In addition, progesterone sequentially upregulates Fas/FasL to induce the caspase-8 and caspase-3 pathways, thereby resulting in increased apoptosis. The combination had a greater effect on the induction of HA22T/VGH cell apoptosis and could potentially serve as a more effective treatment for hepatocellular carcinoma than epirubicin alone. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:432 / 441
页数:10
相关论文
共 42 条
[1]
The Fas/Fas ligand system and cancer [J].
Abrahams, VM ;
Kamsteeg, M ;
Mor, G .
MOLECULAR BIOTECHNOLOGY, 2003, 25 (01) :19-30
[2]
Medroxyprogesterone and tamoxifen augment anti-proliferative efficacy and reduce mitochondria-toxicity of epirubicin in FM3A tumor cells in vitro [J].
Altinoz, Meric A. ;
Bilir, Ayhan ;
Gedikoglu, Gunduz ;
Ozcan, Emin ;
Oktem, Gulperi ;
Muslumanoglu, Mahmut .
CELL BIOLOGY INTERNATIONAL, 2007, 31 (05) :473-481
[3]
Chemotherapy-induced apoptosis of S-type neuroblastoma cells requires caspase-9 and is augmented by CD95/Fas stimulation [J].
Bian, X ;
Giordano, TD ;
Lin, HJ ;
Solomon, G ;
Castle, VP ;
Opipari, AW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (06) :4663-4669
[4]
Management of Hepatocellular Carcinoma: An Update [J].
Bruix, Jordi ;
Sherman, Morris .
HEPATOLOGY, 2011, 53 (03) :1020-1022
[5]
Use of a colorimetric assay to measure differences in cytotoxicity of Mycobacterium tuberculosis strains [J].
Castro-Garza, Jorge ;
Barrios-Garcia, Hugo B. ;
Cruz-Vega, Delia Elva ;
Said-Fernandez, Salvador ;
Carranza-Rosales, Pilar ;
Molina-Torres, Carmen A. ;
Vera-Cabrera, Lucio .
JOURNAL OF MEDICAL MICROBIOLOGY, 2007, 56 (06) :733-737
[6]
Hepatic resection can provide long-term survival of patients with non-early-stage hepatocellular carcinoma: Extending the Indication for resection? [J].
Chang, Wen-Tsan ;
Kao, Wei-Yu ;
Chau, Gar-Yang ;
Su, Chien-Wei ;
Lei, Hao-Jan ;
Wu, Jaw-Ching ;
Hsia, Cheng-Yuan ;
Lui, Wing-Yiu ;
King, Kuang-Liang ;
Lee, Shou-Dong .
SURGERY, 2012, 152 (05) :809-820
[7]
Chang WT, 2010, HEPATO-GASTROENTEROL, V57, P107
[8]
Arecoline induces HA22T/VGH hepatoma cells to undergo anoikis - involvement of STAT3 and RhoA activation [J].
Cheng, Hsiao-Ling ;
Su, Shu-Jem ;
Huang, Li-Wen ;
Hsieh, Bau-Shan ;
Hu, Yu-Chen ;
Hung, Thu-Ching ;
Chang, Kee-Lung .
MOLECULAR CANCER, 2010, 9
[9]
Effects of estradiol and progesterone on tumor necrosis factor alpha-induced apoptosis in human hepatoma HuH-7 cells [J].
Cheng, Xinliang ;
Shimizu, Ichiro ;
Yuan, Ying ;
Wei, Mei ;
Shen, Mi ;
Huang, Huiwei ;
Urata, Mari ;
Sannomiya, Katsutaka ;
Fukuno, Hiroshi ;
Hashimoto-Tamaoki, Tomoko ;
Ito, Susumu .
LIFE SCIENCES, 2006, 79 (21) :1988-1994
[10]
Modulatory effects of progesterone on inducible nitric oxide synthase expression in vivo and in vitro [J].
Coughlan, T ;
Gibson, C ;
Murphy, S .
JOURNAL OF NEUROCHEMISTRY, 2005, 93 (04) :932-942