Search JIM Advanced Search

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

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] Cai-lian Fana, Wan-jun Caib, Meng-nan Ye, Miao Chen, Yi Dai. Qili Qiangxin, a compound herbal medicine formula, alleviates hypoxia-reoxygenation-induced apoptotic and autophagic cell death via suppression of ROS/AMPK/mTOR pathway in vitro. Journal of Integrative Medicine, 2022, 20(4): 365-375.
[2] Hong-xiao Li, Ling Shi, Shang-jie Liang Chen-chen Fang, Qian-qian Xu, Ge Lu, Qian Wang, Jie Cheng, Jie Shen, Mei-hong Shen. Moxibustion alleviates decreased ovarian reserve in rats by restoring the PI3K/AKT signaling pathway. Journal of Integrative Medicine, 2022, 20(2): 163-172.
[3] Mohamed S. Othman, Sofian T. Obeidat, Amal H. Al-Bagawi, Mohamed A. Fareid, Alaa Fehaid, Ahmed E. Abdel Moneim. Green-synthetized selenium nanoparticles using berberine as a promising anticancer agent#br#
#br#
. Journal of Integrative Medicine, 2022, 20(1): 65-72.
[4] Hyongjun Jeon, Hee-Young Kim, Chang-Hwan Bae, Yukyung Lee, Sungtae Koo, Seungtae Kim. Korean red ginseng decreases 1-methyl-4-phenylpyridinium-induced mitophagy in SH-SY5Y cells. Journal of Integrative Medicine, 2021, 19(6): 537-544.
[5] Porwornwisit Tritripmongkol, Tullayakorn Plengsuriyakarn, Mayuri Tarasuk, Kesara Na-Bangchang. In vitro cytotoxic and toxicological activities of ethanolic extract of Kaempferia galanga Linn. and its active component, ethyl-p-methoxycinnamate, against cholangiocarcinoma. Journal of Integrative Medicine, 2020, 18(4): 326-333.
[6] Varuni Colamba Pathiranage, Ira Thabrew, Sameera R. Samarakoon, Kamani H. Tennekoon, Umapriyatharshini Rajagopalan, Meran K. Ediriweera. Evaluation of anticancer effects of a pharmaceutically viable extract of a traditional polyherbal mixture against non-small-cell lung cancer cells. Journal of Integrative Medicine, 2020, 18(3): 242-252.
[7] Maged Mohamed Maher Abou-Hashem, Dina Mohamed Abo-elmatty, Noha Mostafa Mesbah, Ahmed Mohamed Abd EL-Mawgoud. Induction of sub-G0 arrest and apoptosis by seed extract of Moringa peregrina (Forssk.) Fiori in cervical and prostate cancer cell lines. Journal of Integrative Medicine, 2019, 17(6): 410-422.
[8] Supakanya Kumkarnjana, Rutt Suttisri, Ubonthip Nimmannit, Apirada Sucontphunt, Mattaka Khongkow, Thongchai Koobkokkruad, Nontima Vardhanabhuti. Flavonoids kaempferide and 4,2′-dihydroxy-4′,5′,6′-trimethoxychalcone inhibit mitotic clonal expansion and induce apoptosis during the early phase of adipogenesis in 3T3-L1 cells. Journal of Integrative Medicine, 2019, 17(4): 288-295.
[9] Shriniwas S. Basaiyye, Sanjay Kashyap, Kannan Krishnamurthi, Saravanadevi Sivanesan. Induction of apoptosis in leukemic cells by the alkaloid extract of garden cress (Lepidium sativum L.). Journal of Integrative Medicine, 2019, 17(3): 221-228.
[10] Carlos R. Oliveira, Daniel G. Spindola, Daniel M. Garcia, Adolfo Erustes, Alexandre Bechara, Caroline Palmeira-dos-Santos, Soraya S. Smaili, Gustavo J.S. Pereira, André Hinsberger, Ezequiel P. Viriato, Maria Cristina Marcucci, Alexandra C.H.F. Sawaya, Samantha L. Tomaz, Elaine G. Rodrigues, Claudia Bincoletto. Medicinal properties of Angelica archangelica root extract: Cytotoxicity in breast cancer cells and its protective effects against in vivo tumor development. Journal of Integrative Medicine, 2019, 17(2): 132-140.
[11] Bruno José Martins Da Silva, Sandro Wilson Gomes Pereira, Ana Paula Drummond Rodrigues, José Luiz Martins Do Nascimento, Edilene Oliveira Silva. In vitro antileishmanial effects of Physalis angulata root extract on Leishmania infantum. Journal of Integrative Medicine, 2018, 16(6): 404-410.
[12] Eric Wei Chiang Chan, Siu Kuin Wong, Hung Tuck Chan . Casticin from Vitex species: A short review on its anticancer and anti-inflammatory properties. Journal of Integrative Medicine, 2018, 16(3): 147-152.
[13] Jeremiah Olorunjuwon Olugbami, Robert Damoiseaux, Bryan France, Michael A. Gbadegesin, Adam Z. Stieg, Shivani Sharma, Oyeronke A. Odunola, James K. Gimzewski. Atomic force microscopy correlates antimetastatic potentials of HepG2 cell line with its redox/energy status: Effects of curcumin and Khaya senegalensis. Journal of Integrative Medicine, 2017, 15(3): 214-230.
[14] Jesmin Mondal, Asmita Samadder, Anisur Rahman Khuda-Bukhsh. Psorinum 6× triggers apoptosis signals in human lung cancer cells. Journal of Integrative Medicine, 2016, 14(2): 143-153.
[15] Qing-qing Zang, Lu Zhang, Ning Gao, Cheng Huang. Ophiopogonin D inhibits cell proliferation, causes cell cycle arrest at G2/M, and induces apoptosis in human breast carcinoma MCF-7 cells. Journal of Integrative Medicine, 2016, 14(1): 51-59.
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