期刊论文详细信息
BMC Complementary and Alternative Medicine
Fermented So-Cheong-Ryong-Tang (FCY) induces apoptosis via the activation of caspases and the regulation of MAPK signaling pathways in cancer cells
Jin Yeul Ma2  Choong Je Ma1  Taesoo Kim2  Young Pil Jung2  Aeyung Kim2  Nam-Hui Yim2 
[1] Department of Biomaterials Engineering, Division of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, South Korea;KM-Application Center, Korea Institute of Oriental Medicine, 1672, Yuseongdaero, Yuseong, Daejeon 305-811, Republic of Korea
关键词: Xenograft assay;    Mitogen-activated protein kinases (MAPKs);    Caspase activity;    Apoptosis;    Fermentation;    Socheongryong-tang (CY);   
Others  :  1232985
DOI  :  10.1186/s12906-015-0821-2
 received in 2015-05-11, accepted in 2015-08-13,  发布年份 2015
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【 摘 要 】

Background

So-Cheong-Ryong-Tang (CY), a traditional herbal formula, mainly has been shown to possess allergic rhinitis and asthma for hundreds of years in Asian countries. Although this medicine has been attracted Asian scientists with investigating mechanisms of action against inflammatory-related diseases, there is a little available information on the anti-cancer effect of CY, especially on the fermented form (FCY). In this study, we explored the chemopreventive/chemotherapeutic efficacy of FCY against cancer cells and proved the efficacy of FCY through performing in vivo xenograft assay.

Methods

CY was fermented with bacteria and lyophilized. For analysis of the constituents of CY and FCY, high performance liquid chromatography (HPLC)-DAD system was performed. To detect the anti-cancer effect of FCY, cell viability assay, caspase activity assay, cell cycle analysis, and Western blot analysis were performed in AGS human gastric cancer cells. The inhibitory effects of tumor growth by CY and FCY were evaluated in athymic nude mice inoculated with HCT116 human colon cancer cells.

Results

As a result of analyzing the 11components present in CY and FCY, the contents of ephedrine HCl, glycyrrhizin, gingerol, schisandrin, and gomisin A were respectively increased by fermentation in FCY. The treatment of CY or FCY inhibited the viability of AGS cells, interestingly, the inhibition of cancer cell growth was enhanced by fermentation of CY. FCY induced the apoptosis through activating the caspase-3, −8, and −9. Additionally, FCY regulated the activation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK), p38, and c-Jun NH2-terminal kinase (JNK). In vivo xenografts, administration of FCY significantly inhibited the tumor formation, and improved the anti-tumor effect compared to that of CY in athymic nude mice.

Conclusions

FCY indicated significant anti-cancer effects, and its efficacy against tumor formation was improved than that of CY, therefore, FCY might be used for applications of traditional medicine against cancer in modern complementary and alternative therapeutics.

【 授权许可】

   
2015 Yim et al.

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【 参考文献 】
  • [1]Lee HJ, Lee EO, Rhee YH, Ahn KS, Li GX, Jiang C et al.. An oriental herbal cocktail, ka-mi-kae-kyuk-tang, exerts anti-cancer activities by targeting angiogenesis, apoptosis and metastasis. Carcinogenesis. 2006; 27:2455-63.
  • [2]Zhang Z, Wang Y, Yao R, Li J, Yan Y, La Regina M et al.. Cancer chemopreventive activity of a mixture of Chinese herbs (antitumor B) in mouse lung tumor models. Oncogene. 2004; 23:3841-50.
  • [3]Richardson MA, Straus SE. Complementary and alternative medicine: opportunities and challenges for cancer management and research. Semin Oncol. 2002; 29:531-45.
  • [4]Buchanan DR, White JD, O’Mara AM, Kelaghan JW, Smith WB, Minasian LM. Research-design issues in cancer-symptom-management trials using complementary and alternative medicine: lessons from the National Cancer Institute Community Clinical Oncology Program experience. J Clin Oncol. 2005; 23:6682-9.
  • [5]Zha Q, Lin S, Zhang C, Chang C, Xue H, Lu C et al.. Xiaoqinglong granules as add-on therapy for asthma: latent class analysis of symptom predictors of response. Evid Based Complement Alternat Med. 2013; 2013:759476.
  • [6]Tanaka A, Ohashi Y, Kakinoki Y, Washio Y, Yamada K, Nakai Y et al.. The herbal medicine shoseiryu-to inhibits allergen-induced synthesis of tumour necrosis factor alpha by peripheral blood mononuclear cells in patients with perennial allergic rhinitis. Acta Otolaryngol Suppl. 1998; 538:118-25.
  • [7]Hwang MW, Lee HJ, Song HJ, Kim BJ. Involvement of MAPKs and PLC pathways in modulation of pacemaking activity by So-Cheong-Ryong-Tang in interstitial cells of Cajal from murine small intestine. ScientificWorldJournal. 2013; 2013:536350.
  • [8]Zhang C, Feng L, Li M, Dong C, Zhang W. Effects of Xiaoqinglong decoction on gene expression profiles in a rat chronic obstructive pulmonary disease model. Biosci Trends. 2012; 6:262-9.
  • [9]Park C, Hong SH, Kim GY, Choi YH. So-Cheong-Ryong-Tang induces apoptosis through activation of the intrinsic and extrinsic apoptosis pathways, and inhibition of the PI3K/Akt signaling pathway in non-small-cell lung cancer A549 cells. BMC Complement Altern Med. 2015; 15:113. BioMed Central Full Text
  • [10]Lee JS, Oh SY, Seo S, Kim T, Ma JY. Protective effect of Socheongryong-Tang on hydrogen peroxide-induced hepatotoxicity. Korea J Herbology. 2011; 26:133-7.
  • [11]Nam NH, Lee CW, Hong DH, Kim HM, Bae KH, Ahn BZ. Antiinvasive, antiangiogenic and antitumour activity of Ephedra sinica extract. Phytother Res. 2003; 17:70-6.
  • [12]Tang SH, He RR, Huang T, Wang CZ, Cao YF, Zhang Y et al.. The protective effect of Schisandra lignans on stress-evoked hepatic metastases of P815 tumor cells in restraint mice. J Ethnopharmacol. 2011; 134:141-6.
  • [13]Kwon HK, Hwang JS, So JS, Lee CG, Sahoo A, Ryu JH et al.. Cinnamon extract induces tumor cell death through inhibition of NFkappaB and AP1. BMC Cancer. 2010; 10:392. BioMed Central Full Text
  • [14]Dong S, Inoue A, Zhu Y, Tanji M, Kiyama R. Activation of rapid signaling pathways and the subsequent transcriptional regulation for the proliferation of breast cancer MCF-7 cells by the treatment with an extract of Glycyrrhiza glabra root. Food Chem Toxicol. 2007; 45:2470-8.
  • [15]Li GL, Jiang W, Xia Q, Chen SH, Ge XR, Gui SQ et al.. HPV E6 down-regulation and apoptosis induction of human cervical cancer cells by a novel lipid-soluble extract (PE) from Pinellia pedatisecta Schott in vitro. J Ethnopharmacol. 2010; 132:56-64.
  • [16]Elkady AI, Abuzinadah OA, Baeshen NA, Rahmy TR. Differential control of growth, apoptotic activity, and gene expression in human breast cancer cells by extracts derived from medicinal herbs Zingiber officinale. J Biomed Biotechnol. 2012; 2012:614356.
  • [17]Kundoor V, Zhang X, Bommareddy A, Khalifa S, Fahmy H, Dwivedi C. Chemopreventive effects of sarcotriol on ultraviolet B-induced skin tumor development in SKH-1 hairless mice. Mar Drugs. 2007; 5:197-207.
  • [18]Sarfaraz S, Adhami VM, Syed DN, Afaq F, Mukhtar H. Cannabinoids for cancer treatment: progress and promise. Cancer Res. 2008; 68:339-42.
  • [19]Fan M, Chambers TC. Role of mitogen-activated protein kinases in the response of tumor cells to chemotherapy. Drug Resist Updat. 2001; 4:253-67.
  • [20]Dent P, Grant S. Pharmacologic interruption of the mitogen-activated extracellular-regulated kinase/mitogen-activated protein kinase signal transduction pathway: potential role in promoting cytotoxic drug action. Clin Cancer Res. 2001; 7:775-83.
  • [21]Oh YC, Cho WK, Oh JH, Im GY, Jeong YH, Yang MC et al.. Fermentation by Lactobacillus enhances anti-inflammatory effect of Oyaksungisan on LPS-stimulated RAW 264.7 mouse macrophage cells. BMC Complement Altern Med. 2012; 12:17. BioMed Central Full Text
  • [22]Shim KS, Kim T, Ha H, Lee KJ, Cho CW, Kim HS et al.. Lactobacillus fermentation enhances the inhibitory effect of Hwangryun-haedok-tang in an ovariectomy-induced bone loss. BMC Complement Altern Med. 2013; 13:106. BioMed Central Full Text
  • [23]Oh YC, Cho WK, Jeong YH, Im GY, Yang MC, Ma JY. Fermentation improves anti-inflammatory effect of sipjeondaebotang on LPS-stimulated RAW 264.7 cells. Am J Chin Med. 2012; 40:813-31.
  • [24]Weon JB, Yang HJ, Lee B, Ma JY, Ma CJ. Simultaneous quantification of eleven chemical components in traditional herbal medicinal formula socheongryongtang by HPLC-DAD and LC-MS. J Liq Chromatogr Relat Technol. 2012; 35:2243-54.
  • [25]Shimada T, Kondoh M, Motonaga C, Kitamura Y, Cheng L, Shi H et al.. Enhancement of anti-allergic effects mediated by the Kampo medicine Shoseiryuto (Xiao-Qing-Long-Tang in Chinese) with lysed Enterococcus faecalis FK-23 in mice. Asian Pac J Allergy Immunol. 2010; 28:59-66.
  • [26]Yim NH, Jung YP, Kim A, Ma CJ, Cho WK, Ma JY. Oyaksungisan, a traditional herbal formula, inhibits cell proliferation by induction of autophagy via JNK activation in human colon cancer cells. Evid Based Complement Alternat Med. 2013; 2013:231874.
  • [27]Corson TW, Crews CM. Molecular understanding and modern application of traditional medicines: triumphs and trials. Cell. 2007; 130:769-74.
  • [28]Xue T, Roy R. Studying traditional Chinese medicine. Science. 2003; 300(5620):740-1.
  • [29]Ko E, Rho S, Cho C, Choi H, Ko S, Lee Y et al.. So-Cheong-Ryong-Tang, tradititional Korean medicine, suppresses Th2 lineage development. Biol Pharm Bull. 2004; 27:739-43.
  • [30]Saraste A, Pulkki K. Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res. 2000; 45:528-37.
  • [31]Sheikh MS, Huang Y. Death receptors as targets of cancer therapeutics. Curr Cancer Drug Targets. 2004; 4:97-104.
  • [32]Vermeulen K, Van Bockstaele DR, Berneman ZN. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 2003; 36:131-49.
  • [33]Bartek J, Lukas J. Mammalian G1- and S-phase checkpoints in response to DNA damage. Curr Opin Cell Biol. 2001; 13:738-47.
  • [34]Lobrich M, Jeggo PA. The impact of a negligent G2/M checkpoint on genomic instability and cancer induction. Nat Rev Cancer. 2007; 7:861-9.
  • [35]Murphy LO, Blenis J. MAPK signal specificity: the right place at the right time. Trends Biochem Sci. 2006; 31:268-75.
  • [36]Scalbert A, Williamson G. Dietary intake and bioavailability of polyphenols. J Nutr. 2000; 130:2073S-85.
  • [37]Izumi T, Piskula MK, Osawa S, Obata A, Tobe K, Saito M et al.. Soy isoflavone aglycones are absorbed faster and in higher amounts than their glucosides in humans. J Nutr. 2000; 130:1695-9.
  • [38]Schubert SY, Lansky EP, Neeman I. Antioxidant and eicosanoid enzyme inhibition properties of pomegranate seed oil and fermented juice flavonoids. J Ethnopharmacol. 1999; 66:11-7.
  • [39]Hibasami H, Iwase H, Yoshioka K, Takahashi H. Glycyrrhizin induces apoptosis in human stomach cancer KATO III and human promyelotic leukemia HL-60 cells. Int J Mol Med. 2005; 16:233-6.
  • [40]Kim SJ, Min HY, Lee EJ, Kim YS, Bae K, Kang SS et al.. Growth inhibition and cell cycle arrest in the G0/G1 by schizandrin, a dibenzocyclooctadiene lignan isolated from Schisandra chinensis, on T47D human breast cancer cells. Phytother Res. 2010; 24:193-7.
  • [41]Waiwut P, Shin MS, Yokoyama S, Saiki I, Sakurai H. Gomisin A enhances tumor necrosis factor-alpha-induced G1 cell cycle arrest via signal transducer and activator of transcription 1-mediated phosphorylation of retinoblastoma protein. Biol Pharm Bull. 2012; 35:1997-2003.
  • [42]Chakraborty D, Bishayee K, Ghosh S, Biswas R, Mandal SK, Khuda-Bukhsh AR. [6]-Gingerol induces caspase 3 dependent apoptosis and autophagy in cancer cells: drug-DNA interaction and expression of certain signal genes in HeLa cells. Eur J Pharmacol. 2012; 694:20-9.
  • [43]Lin CB, Lin CC, Tsay GJ. 6-gingerol inhibits growth of colon cancer cell LoVo via induction of G2/M arrest. Evid Based Complement Alternat Med. 2012; 2012:326096.
  • [44]Jeong CH, Bode AM, Pugliese A, Cho YY, Kim HG, Shim JH et al.. [6]-Gingerol suppresses colon cancer growth by targeting leukotriene A4 hydrolase. Cancer Res. 2009; 69:5584-91.
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