[an error occurred while processing this directive]

Journal of Chinese Integrative Medicine ›› 2007, Vol. 5 ›› Issue (3): 298-301.doi: 10.3736/jcim20070313

• Original Experimental Research • Previous Articles     Next Articles

Effects of NK-104 on apoptosis and caspase-3 activity in hepatocellular carcinoma cells

Ju-yong Wang, Zhen-ye Xu   

  1. Institute of Oncology of Traditional Chinese Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai 200032, China
  • Online:2007-05-31 Published:2007-05-15

RichHTML

1

PDF (PC)

285

Like

Objective: To study the apoptosis of human hepatocellular carcinoma cell line HepG 2 induced by pitavastatin (NK-104) and to investigate the change of caspase-3 activity.Methods: HepG 2 cells were treated with NK-104 for 48 hours and observed under a microscope by using Hoechst 33258 staining. The proliferation of the cells was detected with WST-8 method. The apoptosis peaks were examined by flow cytometry. The caspase-3 activity was detected with caspase-3 colorimetric protease assay. Results: The treatment of HepG 2 with 10 μmol/L NK-104 could inhibit the proliferation, and induce HepG 2 apoptosis and up-regulate the caspase-3 activity. Conclusion: NK-104 at 10 μmol/L induces apoptosis of HepG 2 cells. It is dependent on caspase-3 pathway in human hepatocellular carcinoma cells.

Key words: apoptosis, caspase, cancer of liver, microscopy, fluorescence

CLC Number: 

  • R735.7

Figure 1

Growth inhibition of HepG 2 cells by NK-104**P＜0.01, vs control group."

Figure 2

Nuclear morphology of the HepG 2 cells treated by NK-104 for 48 hours (Hoeschst 33258 staining, ×400)A: Control, normal nuclear structure; B: NK-104 10 μmol/L; C: NK-104 100 μmol/L; D: Cytoplasmic change; E: Nuclear fragmentation."

Figure 3

Cell cycle analysis of HepG 2 cells treated by NK-104 (Percentage of Sub G1 cells)**P＜0.01, vs control group. A: Control; B: NK-104 10 μmol/L; C: NK-104+MEV."

Figure 4

NK-104 induced activity of caspase-3**P＜0.01, vs control group. The HepG 2 cells were exposed to NK-104 (10 μmol/L) alone, or NK-104 (10 μmol/L) plus MEV (1 mmol/L) for 48 hours. The caspase-3 activity was measured with a colorimetric protease assay."

[1] Goldstein JL, Brown MS . Regulation of the mevalonate pathway[J]. Nature, 1990,34(3):425-430
[2] Bellost S, Paoletti R. Corsini A . Safe of statins: focus on clinical pharmacokinetics and drug interactions[J]. Circulation, 2004,109(SupplⅢ):50-57
[3] Chan KK, Oza AM, Siu LL . The statins as anticancer agents[J]. Clin Cancer Res, 2003,9(1):10-19
doi: 10.1007/BF02681822 pmid: 23483876
[4] Kajinami K, Takekoshi N, Saito Y . Pitavastatin: efficacy and safety profiles of a novel synthetic HMG-CoA reductase inhibitor[J]. Cardiovasc Drug Rev, 2003,21(3):199-215
doi: 10.1111/j.1527-3466.2003.tb00116.x pmid: 12931254
[5] Wang J, Tokoro T, Matsui K , et al. Pitavastatin at low dose activates endothelial nitric oxide synthase through PI3K-AkT pathway in endothelial cells[J]. Life Sci, 2005,76(19):2257-2268
[6] 陈建国, 宋新明 . 中国肝癌发病水平的估算及分析[J]. 中国肿瘤, 2005,14(1):28-31
Chen JG, Song XM . An evaluation on incident cases of liver cancer in China[J]. Zhongguo Zhong Liu, 2005,14(1):28-31
[7] Otsuki T, Sakaguchi H, Hatayama T , et al. Effects of an HMG-CoA reductase inhibitor, simvastatin, on human myeloma cells[J]. Oncol Rep, 2004,11(5):1053-1058
doi: 10.3892/or.11.5.1053 pmid: 15069546
[8] Sutter AP, Masser K, Hopfiner M , et al. Cell cycle arrest and apoptosis induction in hepatocellular carcinoma cells by HMG-CoA reductase inhibitors. Synergistic antiproliferative action with ligands of the peripheral benzodiazepine receptor[J]. J Hepatol, 2005,43(5):808-816
[9] Denoyelle C, Vasse M, Korner M , et al. Cerivastatin, an inhibitor of HMG-CoA reductase, inhibits the signaling pathways involved in the invasiveness and metastatic properties of highly invasive breast cancer cell lines: an in vitro study[J]. Carcinogenesis, 2001,22(8):1139-1148
[10] Nilsson C, Kagedal K, Johansson U , et al. Analysis of cytosolic and lysosomal pH in apoptotic cells by flow cytometry[J]. Methods Cell Sci, 2004,25(3-4):185-194
doi: 10.1007/s11022-004-8228-3 pmid: 15801164
[11] Chen YC, Shen SC, Lee WR , et al. Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production[J]. Biochem Pharmacol, 2002,64(12):1713-1724
doi: 10.1016/S0006-2952(02)01386-2
[12] 周喜乐, 郑树森, 谢海洋 . 半胱氨酸酶-3在依托利酸诱导肝癌细胞凋亡中的作用[J]. 中华实验外科杂志, 2004,21(5):551-553
Zhou XL, Zheng SS, Xie HY . Significance of caspase-3 in etodolac-induced apoptosis of SMMC7721 cell line[J]. Zhonghua Shi Yan Wai Ke Za Zhi, 2004,21(5):551-553
[13] 郑世营, 葛锦锋, 赵军 , 等. 外源性FasL基因诱导肺癌细胞Caspase-3的表达及凋亡[J]. 肿瘤防治杂志, 2004,11(3):273-277
Zheng SY, Ge JF, Zhao J , et al. Expression of caspase-3 gene in human lung adenocarcinoma cell line A-549 with Ad-FasL[J]. Zhong Liu Fang Zhi Za Zhi, 2004,11(3):273-277
[14] Li X, Darzynkiewicz Z . Cleavage of poly(ADP-ribose) polymerase measured in situ individual cells: relationship to DNA fragmentation and cell cycle position during apoptosis[J]. Exp Cell Res, 2000,255(1):125-132
[1] Avijit Paul, Kausik Bishayee, Samrat Ghosh, Avinaba Mukherjee, Sourav Sikdar, Debrup Chakraborty, Naoual Boujedaini, Anisur Rahman Khuda-Bukhsh. Chelidonine isolated from ethanolic extract of Chelidonium majus promotes apoptosis in HeLa cells through p38-p53 and PI3K/AKT signalling pathways. Journal of Chinese Integrative Medicine, 2012, 10(9): 1025-1038.
[2] Yogesh Bendale, Vineeta Bendale, Saili Paul, Soumya Sundar Bhattacharyya. Green synthesis, characterization and anticancer potential of platinum nanoparticles Bioplatin. Journal of Chinese Integrative Medicine, 2012, 10(6): 681-689.
[3] Samadder Asmita, Das Jayeeta, Das Sreemanti, Das Durba, De Arnab, Bhadra Kakali, Rahman Khuda-Bukhsh Anisur. Dihydroxy-isosteviol methyl ester of Pulsatilla nigricans extract reduces arsenic-induced DNA damage in testis cells of male mice: Its toxicity, drug-DNA interaction and signaling cascades. Journal of Chinese Integrative Medicine, 2012, 10(12): 1433-1442.
[4] Min Zhu , Mi Zhou , Ying Shi , Wen-wei Li. Effects of echinacoside on MPP+-induced mitochondrial fragmentation, mitophagy and cell apoptosis in SH-SY5Y cells. Journal of Chinese Integrative Medicine, 2012, 10(12): 1427-1432.
[5] Mukherjee Avinaba, Sikdar Sourav, Bishayee Kausik, Paul Avijit, Ghosh Samrat, Boujedaini Naoual, Rahman Khuda-Bukhsh Anisur. Ethanolic extract of Thuja occidentalis blocks proliferation of A549 cells and induces apoptosis in vitro. Journal of Chinese Integrative Medicine, 2012, 10(12): 1451-1459.
[6] Xiao-ping Huang , Xiao-dan Liu , Chang-qing Deng . Effects of the combination of active component extracts from Astragalus membranaceus and Panax notoginseng on apoptosis, reactive oxygen species and mitochondrial membrane potential of PC12 cells with oxidative injury. Journal of Chinese Integrative Medicine, 2012, 10(10): 1127-1134.
[7] Agung E. Nugroho, Adam Hermawan, Dyaningtyas D. P. Putri, E. dY Meiyanto, Lukman Hakim . Synergistic effects of ethyl acetate fraction of Ficus septica Burm. f. and doxorubicin chemotherapy on T47D human breast cancer cell line. Journal of Chinese Integrative Medicine, 2012, 10(10): 1162-1170.
[8] Hao Dai, Jun Gu, Ling-zhi Li, Li-mei Yang, Hui Liu, Jian-yu Li. Scutellarin benzyl ester partially secured the ischemic injury by its anti-apoptosis mechanism in cardiomyocytes of neonatal rats. Journal of Chinese Integrative Medicine, 2011, 9(9): 1014-1021.
[9] Yu Miao, Yue-rong Jiang, Lin Yang, Cheng-dong Xia, Lu Zhang, Cai-feng Wu, Da-zhuo Shi, Hui-jun Yin, Ke-ji Chen. Effects of Chinese herbal drug-containing serum on oxidative damage and apoptosis of umbilical vein endothelial cells induced by oxidized low-density lipoprotein. Journal of Chinese Integrative Medicine, 2011, 9(5): 539-545.
[10] Zhao-hui Chu, Xiao-hua Liang, Xin-li Zhou, Ruo-fan Huang, Qiong Zhan, Jing-wei Jiang. Effects of deguelin on proliferation and apoptosis of MCF-7 breast cancer cells by phosphatidylinositol 3-kinase/Akt signaling pathway. Journal of Chinese Integrative Medicine, 2011, 9(5): 533-538.
[11] Bo Yang, Xue-chun Lu, Feng Zhang, Yang Liu, Hong-li Zhu. Inhibitory effects of traditional Chinese herbal medicine Tanreqing injection on proliferation of leukemia cells in vitro and the potential mechanisms. Journal of Chinese Integrative Medicine, 2011, 9(4): 414-422.
[12] Khuda-Bukhsh AR, Bhattacharyya SS, Paul S, Boujedaini N. Polymeric nanoparticle encapsulation of a naturally occurring plant scopoletin and its effects on human melanoma cell A375. Journal of Chinese Integrative Medicine, 2010, 8(9): 853-862.
[13] Bing Hu, Hong-mei An, Ke-ping Shen, Qin Du. Effects of Tenglong Buzhong Decoction on proliferation and apoptosis of human colon carcinoma cell line LS174T. Journal of Chinese Integrative Medicine, 2010, 8(6): 575-580.
[14] Qing-hua Peng , Xiao-lei Yao, Quan-long Wu, Han-yu Tan, Jing-rong Zhang. Effects of eye drops of Buddleja officinalis Maxim. extract on lacrimal gland cell apoptosis in castrated rats with dry eye. Journal of Chinese Integrative Medicine, 2010, 8(3): 244-249.
[15] Xue-ying Wang, Jie Wang, Ge Yang, Yong-mei Liu. Effects of Xuesaitong Soft Capsule on hemodynamics and cardiocyte apoptosis of rats after myocardial infarction. Journal of Chinese Integrative Medicine, 2010, 8(3): 269-274.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[2] Hai-feng Wei, Bai-liu Ya, Ling Zhao, Cui-fei Ye, Li Zhang, Lin Li. Evaluation of tongue manifestation of blood stasis syndrome and its relationship with blood rheological disorder in a rat model of transient brain ischemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 73-76
[3] Xi Lin, Jian-ping Liu. Herbal medicines for viral myocarditis. Journal of Chinese Integrative Medicine, 2008, 6(1): 76
[4] Xi Lin, Jian-ping Liu. Tai chi for treating rheumatoid arthritis. Journal of Chinese Integrative Medicine, 2008, 6(1): 82
[5] Liang-ping Hu, Hui Gao. Discrimination of errors in statistical analysis of medical papers published in the first issue of 2006 in Journal of Chinese Integrative Medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 98-106
[6] Yan-bo Zhu , Qi Wang, Cheng-yu Wu, Guo-ming Pang, Jian-xiong Zhao, Shi-lin Shen, Zhong-yuan Xia , Xue Yan . Logistic regression analysis on relationships between traditional Chinese medicine constitutional types and overweight or obesity. Journal of Chinese Integrative Medicine, 2010, 8(11): 1023-1035
[7] Wei Xu, Meng Shi, Jian-gang Liu, Cheng-long Wang . Collagen protein expressions in ischemic myocardium of rats with acute myocardial infarction and effects of qi-tonifying, yin-tonifying and blood-activating herbs and detoxifying and blood-activating herbs. Journal of Chinese Integrative Medicine, 2010, 8(11): 1041-1047
[8] Tao Wang , Feng Qin. Effects of Chinese herbal medicine Xiaoyao Powder on monoamine neurotransmitters in hippocampus of rats with postpartum depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1075-1079
[9] Ying Xu , Chang-chun Zeng , Xiu-yu Cai , Rong-ping Guo , Guang Nie , Ying Jin. Chromaticity and optical spectrum colorimetry of the tongue color in different syndromes of primary hepatic carcinoma. Journal of Chinese Integrative Medicine, 2012, 10(11): 1263-1271
[10] Xiang-ying Mao , Qin Bian , Zi-yin Shen. Analysis of the osteogenetic effects exerted on mesenchymal stem cell strain C3H10T1/2 by icariin via MAPK signaling pathway in vitro. Journal of Chinese Integrative Medicine, 2012, 10(11): 1272-1278
[an error occurred while processing this directive]