Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2010, Vol. 8 ›› Issue (11): 1048-1052.doi: 10.3736/jcim20101108

• Original Expreimental Research • Previous Articles     Next Articles

Senescence-inducing effects of Chinese herbal medicine Tenglong Buzhong Decoction on human colon carcinoma LS-174-T cells and the mechanism

Bing Hu a,b,Hong-mei Anc,Ke-ping Shena, Qin Dua   

  1. a 5th Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
    b E-institute of Internal Medicine of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    c Department of Science and Technology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
  • Received:2010-02-23 Accepted:2010-07-13 Online:2010-11-20 Published:2010-11-15
  • Contact: Bing Hu E-mail:beearhu@hotmail.com

Objective

Cell senescence is an important anti-cancer mechanism and may contribute to cancer therapeutic outcome. The present study observed the effects of Tenglong Buzhong Decoction (TLBZD), a Chinese herbal formula, on senescence in human colon carcinoma LS-174-T cells.

Methods

LS-174-T cells were treated with TLBZD, and morphology change was observed under a microscope. Cell senescence was identified by senescence-associated β-galactosidase (SA-β-gal) staining, and cell cycle was analyzed by flow cytometry. Expressions of p53, p21 WAF1/CIP1, p16 and RB and RB phosphorylation were detected by Western blot.

Results

After being treated with TLBZD, LS-174-T cells became enlarged and flattened by morphology; SA-β-gal staining was positive and cell cycle was arrested in G0/G1. In addition, up-regulations of p21 WAF1/CIP1 and p16, as well as inhibition of RB phosphorylation were detected in response to TLBZD treatment. Expressions of p53 and RB were unchanged after TLBZD treatment.

Conclusion

TLBZD is effective in inducing cell senescence in human colon carcinoma LS-174-T cells, which may relate to up-regulations of p21 WAF1/CIP1 and p16 and inhibition of RB phosphorylation.

Key words: Colonic neoplasms, Chinese herbal drugs, Cell senescence, Signal transduction

Figure 1

Effects of TLBZD on activities of SA-β-gal in LS-174-T cells and CRL-1790 cells (Light microscopy, ×200) A and B: LS-174-T cells; C and D: CRL-1790 cells; A and C: ddH2O; B and D: TLBZD."

Figure 2

Effects of TLBZD on cell cycle in LS-174-T cells"

Table 1

Effects of TLBZD on cell cycle in LS-174-T cells"

Figure 3

Effects of TLBZD on expressions of senescence-related genes in LS-174-T cells"

[1] Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ . Cancer statistics, 2009[J]. CA Cancer J Clin, 2009,59(4):225-249
doi: 10.3322/caac.20006
[2] Yance DR Jr, Sagar SM . Targeting angiogenesis with integrative cancer therapies[J]. Integr Cancer Ther, 2006,5(1):9-29
doi: 10.1177/1534735405285562
[3] Sagar SM, Yance D, Wong RK . Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer — Part 1[J]. Curr Oncol, 2006,13(1):14-26
[4] Chiantore MV, Vannucchi S, Mangino G, Percario ZA, Affabris E, Fiorucci G, Romeo G . Senescence and cell death pathways and their role in cancer therapeutic outcome[J]. Curr Med Chem, 2009,16(3):287-300
doi: 10.2174/092986709787002691
[5] Gewirtz DA, Holt SE, Elmore LW . Accelerated senescence: an emerging role in tumor cell response to chemotherapy and radiation[J]. Biochem Pharmacol, 2008,76(8):947-957
doi: 10.1016/j.bcp.2008.06.024 pmid: 18657518
[6] Hsu YL, Kuo PL, Tzeng TF, Sung SC, Yen MH, Lin LT, Lin CC . Huang-lian-jie-du-tang, a traditional Chinese medicine prescription, induces cell-cycle arrest and apoptosis in human liver cancer cells in vitro and in vivo[J]. J Gastroenterol Hepatol, 2008,23(7 Pt 2):e290-e299
doi: 10.1111/jgh.2008.23.issue-7pt2
[7] Kao ST, Yeh CC, Hsieh CC, Yang MD, Lee MR, Liu HS, Lin JG . The Chinese medicine Bu-Zhong-Yi-Qi-Tang inhibited proliferation of hepatoma cell lines by inducing apoptosis via G0/G1 arrest[J]. Life Sci, 2001,69(13):1485-1496
doi: 10.1016/S0024-3205(01)01226-7
[8] Du P, Lu JF . Effect of Zuogui Pill extracts of water extracting-alcohol precipitation on rat ovarian granulosa cell growth in vitro[J]. Zhong Yao Yao Li Yu Lin Chuang, 2007,23(1):9-10
杜萍, 卢金福 . 左归丸水提醇沉液对体外培养大鼠卵巢颗粒细胞生长的影响[J]. 中药药理与临床, 2007,23(1):9-10
[9] Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, Peacocke M, Campisi S . A biomarker that identifies senescent human cells in culture and in aging skin in vivo[J]. Proc Natl Acad Sci U S A, 1995,92(20):9363-9367
doi: 10.1073/pnas.92.20.9363 pmid: 7568133
[10] Hu B, An HM, Shen KP . Cellular senescence and carcinogenesis[J]. Sheng Ming Ke Xue, 2008,20(3):447-449
doi: 10.3760/cma.j.issn.1673-422X.2010.10.001
胡兵, 安红梅, 沈克平 . 细胞衰老与肿瘤发生[J]. 生命科学, 2008,20(3):447-449
doi: 10.3760/cma.j.issn.1673-422X.2010.10.001
[11] Chen Z, Trotman LC, Shaffer D, Lin HK, Dotan ZA, Niki M, Koutcher JA, Scher HI, Ludwig T, Gerald W, Cordon-Cardo C, Pandolfi PP . Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis[J]. Nature, 2005,436(7051):725-730
doi: 10.1038/nature03918 pmid: 16079851
[12] Michaloglou C, Vredeveld LC, Soengas MS, Denoyelle C, Kuilman T, van der Horst CM, Majoor DM, Shay JW, Mooi WJ, Peeper DS. BRAFE600-associated senescence-like cell cycle arrest of human naevi[J]. Nature, 2005,436(7051):720-724
doi: 10.1038/nature03890 pmid: 16079850
[13] Collado M, Gil J, Efeyan A, Guerra C, Schuhmacher AJ, Barradas M, Bengur a A,Zaballos A,Flores JM,Barbacid M,Beach D,Serrano M. Tumour biology: senescence in premalignant tumours[J]. Nature, 2005,436(7051):642
doi: 10.1038/436642a
[14] Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, Schlegelberger B, Stein H , Dörken B, Jenuwein T, Schmitt CA. Oncogene-induced senescence as an initial barrier in lymphoma development[J]. Nature, 2005,436(7051):660-665
doi: 10.1038/nature03841 pmid: 16079837
[15] Han Z, Wei W, Dunaway S, Darnowski JW, Calabresi P, Sedivy J, Hendrickson EA, Balan KV, Pantazis P, Wyche JH . Role of p21 in apoptosis and senescence of human colon cancer cells treated with camptothecin[J]. J Biol Chem, 2002,277(19):17154-17160
doi: 10.1074/jbc.M112401200
[16] Thaler S, Hähnel PS, Schad A, Dammann R, Schuler M . RASSF1A mediates p21Cip1/Waf1-dependent cell cycle arrest and senescence through modulation of the Raf-MEK-ERK pathway and inhibition of Akt[J]. Cancer Res, 2009,69(5):1748-1757
doi: 10.1158/0008-5472.CAN-08-1377
[17] Aliouat-Denis CM, Dendouga N, Van den Wyngaert I, Goehlmann H, Steller U, van de Weyer I, Van Slycken N, Andries L,Kass S,Luyten W,Janicot M,Vialard JE. p53-independent regulation of p21WAF1/CIP1 expression and senescence by Chk2[J]. Mol Cancer Res, 2005,3(11):627-634
doi: 10.1158/1541-7786.MCR-05-0121 pmid: 16317088
[18] Kang JY, Kim JJ, Jang SY, Bae YS . The p53-p21Cip1/Waf1 pathway is necessary for cellular senescence induced by the inhibition of protein kinase CKII in human colon cancer cells[J]. Mol Cells, 2009,28(5):489-494
doi: 10.1007/s10059-009-0141-9
[19] Papazoglu C , Mills AA.p53: at the crossroad between cancer and ageing[J]. J Pathol, 2007,211(2):124-133
doi: 10.1002/path.2086 pmid: 17200941
[20] Varna M, Lehmann-Che J, Turpin E, Marangoni E, El-Bouchtaoui M, Jeanne M, Grigoriu C, Ratajczak P, Leboeuf C, Plassa LF, Ferreira I, Poupon MF , Janin A, de Thé H, Bertheau P.p53 dependent cell-cycle arrest triggered by chemotherapy in xenografted breast tumors[J]. Int J Cancer, 2009,124(4):991-997
doi: 10.1002/ijc.24049 pmid: 19048622
[21] Dimri GP . What has senescence got to do with cancer[J]. Cancer Cell, 2005,7(6):505-512
doi: 10.1016/j.ccr.2005.05.025 pmid: 1769521
[1] Paul Avijit, Das Sreemanti, Das Jayeeta, Samadder Asmita, Bishayee Kausik, Sadhukhan Ratan, Anisur Rahman Khuda-Bukhsh. Diarylheptanoid-myricanone isolated from ethanolic extract of Myrica cerifera shows anticancer effects on HeLa and PC3 cell lines: Signalling pathway and drug-DNA interaction. Journal of Chinese Integrative Medicine, 2013, 11(6): 405-415.
[2] Yong Zhang, Xiao-wen Sun, Jian-hua Xu, Hai Lu, Zhong-ze Fan, Jue Sun, Xiao-xiao Zhang. Effects of medicated serum prepared with Chinese herbal medicine Changweiqing on pharmacokinetics of oxaliplatin in colon cancer cells. Journal of Chinese Integrative Medicine, 2012, 10(8): 901-910.
[3] Gang Guo, Jian-hua Xu, Jian-hong Han, Fang Liang, Yong Zhang, Qiang Zhang, Jue Sun, Zhong-ze Fan . Chinese herbal decoction Shiquan Dabu Tang inhibits tumor growth and angiogenesis of metastasis after primary tumor surgical removal in mice. Journal of Chinese Integrative Medicine, 2012, 10(4): 436-447.
[4] Jin-bin Han, Yong-qiang Hua, Lian-yu Chen, Lu-ming Liu . Advances in Smoothened-targeting therapies for pancreatic cancer: Implication for drug discovery from herbal medicines. Journal of Chinese Integrative Medicine, 2012, 10(3): 256-263.
[5] Yang Chen, Jian-hua Huang, You Ning, Zi-yin Shen. Icariin and its pharmaceutical efficacy: Research progress of molecular mechanism. Journal of Chinese Integrative Medicine, 2011, 9(11): 1179-1184.
[6] Shou-fu Wang, Hui-jian Zhang, Jian-sheng Li, Jin-li Qin, Su-yun Li, Hai-bin Yu, Feng Wang, Ya Li, Si-hua Liu. Effects of Chinese herbal medicine Dusuqing Granule on toll-like receptor 4 signaling in multiple organ injury induced by bacterial pneumonia in aged rats. Journal of Chinese Integrative Medicine, 2011, 9(1): 84-90.
[7] Ming-hui Yang, Min Li, Yong-qi Dou, Yi Liu, Xiao-dong Luo, Jian-zong Chen, Heng-jun Shi. Effects of Bushen Huoxue Granule on motor function in patients with Parkinson’s disease: A multicenter, randomized, double-blind and placebo-controlled trial. Journal of Chinese Integrative Medicine, 2010, 8(3): 231-237.
[8] Ya-bing Zhou, Jian-er Yu, Jie Wu, Li Bai, Li-li Huo, Xin-guang Zhang, Li-qing Li . Effects of Chinese herbal medicine Bushen Gubiao Recipe on toll-like receptor 4 and CD4 +CD25 +foxp3 +regulatory T cells in mice with recurrent respiratory tract infections. Journal of Chinese Integrative Medicine, 2010, 8(11): 1053-1059.
[9] 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.
[10] Li Yan, Xian-chuan Chen, Jian Guo, Li-li Qi, Yi-ming Qian, Xiong-gen Zhou. Prevention of hospital-acquired pneumonia with Yupingfeng Powder in patients with acute cerebral vascular diseases: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2010, 8(1): 25-29.
[11] Wen-jun Wang, Da-jin Li, Jun Li, Wen-jiang Zhou. An in vitro study on neuroprotective effects of serum containing Gengnianchun decoction and its main monomers against amyloid beta protein-induced cellular toxicity. Journal of Chinese Integrative Medicine, 2010, 8(1): 67-73.
[12] Xin-yue Zhi . Traditional Chinese medicine diagnosis and treatment of type 2 diabetes in Tianjin urban population. Journal of Chinese Integrative Medicine, 2009, 7(9): 823-826.
[13] Deng-hao Liu, Zheng Wang, Zhang-yan Qin. Clinical effects of Shugan Jianpi Recipe on postadolescent acne in women. Journal of Chinese Integrative Medicine, 2009, 7(7): 671-673.
[14] Xin-jun Liu, Shi-bing Su. Study of combination methods for formula composition of Chinese herbal medicines and their components. Journal of Chinese Integrative Medicine, 2009, 7(7): 601-606.
[15] Xian-jun Tong, Xiao-yu Xiang, Zun-hua Cheng, Li Chen, Xian-chuan Chen, Jing-xian Chen. Color Doppler ultrasound evaluation of a Chinese herbal formula in treating lower limb arteriosclerosis: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2009, 7(6): 518-521.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] Jin-rong Fu. Establishment of multivariate diagnosis and treatment system of modern gynecology of traditional Chinese medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 22-24
[2] Hao Li, Ming-jiang Yao, Wen-ming Zhao, Jie Guan, Lin-lin Cai, Ling Cui. A randomized, controlled, double-blind trial of Huannao Yicong capsule in senile patients with mild cognitive impairment. Journal of Chinese Integrative Medicine, 2008, 6(1): 25-31
[3] Zhi-chun Jin. Problems in establishing clinical guideline for integrated traditional Chinese and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 5-8
[4] SUN Ming-yu, ZUO Jian, DUAN Ji-feng, HAN Jun, FAN Shi-ming, ZHANG Wei, ZHU Li-fang, YAO Ming-hui. Antitumor activities of kushen flavonoids in vivo and in vitro. Journal of Chinese Integrative Medicine, 2008, 6(1): 51-59
[5] Min Cheng, Qiong Feng, Shu-wen Qian, Hui Gao, Cui-qing Zhu. Preliminary assay of p-amyloid binding elements in heart-beneficial recipe. Journal of Chinese Integrative Medicine, 2008, 6(1): 68-72
[6] Ning-qun Wang, Liang-duo Jiang, Zong-xing Li. Research progress in asthma-related quality of life. Journal of Chinese Integrative Medicine, 2008, 6(1): 93-97
[7] Jing-yuan Mao, Chang-xiao Liu, Heng-he Wang, Guang-li Wei , Zhen-peng Zhang, Jie Xing, Wang Xian liang , Ying-fei Bi . Effects of Shenmai Injection on serum concentration and pharmacokinetics of digoxin in dogs with heart failure. Journal of Chinese Integrative Medicine, 2010, 8(11): 1070-1074
[8] Zhi-mei Wang, Bin Zhang. A study on translation of ellipses in Huangdi Neijing from perspective of hermeneutic theory. Journal of Chinese Integrative Medicine, 2010, 8(11): 1097-1100
[9] Gui Yu, Jie Wang. Thinking on building the network cardiovasology of Chinese medicine. Journal of Chinese Integrative Medicine, 2012, 10(11): 1206-1210
[10] Pedro Saganha João, Doenitz Christoph, Greten Tobias, Efferth Thomas, J. Greten Henry. Qigong therapy for physiotherapists suffering from burnout: a preliminary study. Journal of Chinese Integrative Medicine, 2012, 10(11): 1233-1239