Herbal extract “Songyou Yin” inhibits tumor growth and prolongs survival in nude mice bearing human hepatocellular carcinoma xenograft with high metastatic potential | springermedizin.de

Springer Medizin

nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.09.2009 | Original Paper

Herbal extract “Songyou Yin” inhibits tumor growth and prolongs survival in nude mice bearing human hepatocellular carcinoma xenograft with high metastatic potential

verfasst von: Xiu-Yan Huang, Lu Wang, Zi-Li Huang, Qi Zheng, Qi-Song Li, Zhao-You Tang

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 9/2009

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Chinese herbs have become a focus of interest in cancer treatment. This study evaluates the effect of the herbal compound extract “Songyou Yin” (containing Salvia miltiorrhiza Bge.-danshen and other four herbs) on hepatocellular carcinoma (HCC).

Methods

Human HCC cell line MHCC97H with high-metastatic potential was employed for in vitro study. In vivo study was conducted in nude mice bearing HCC orthotopic xenograft with MHCC97H.

Results

In vitro, “Songyou Yin” caused dramatic attenuation of tumor proliferation by induction of apoptosis that was associated with caspase-3 activation, and inhibit invasiveness of MHCC97H via reducing matrix metalloproteinase-2 (MMP2) activity. In vivo, “Songyou Yin” minimized cancer-related body weight loss of mice bearing tumors without distinct toxicity, and inhibited tumor growth with stepwise increased dosage of “Songyou Yin” and accorded with the expression of proliferating cell nuclear antigen. Moreover, “Songyou Yin” inhibited tumor growth was associated with an increased TUNEL-positive apoptosis as well as a decreased microvessel density and vascular endothelial growth factor (VEGF) abundance, and inhibited tumor invasion via down-regulation of MMP2. The lung metastatic extent was decreased (p < 0.01, compared with control). The life span of nude mice bearing xenografts was 75.0 ± 3.9 days in “Songyou Yin” group, whereas it was 52.0 ± 2.3 days in the control (p < 0.001).

Conclusions

Nontoxic herbal compound extract “Songyou Yin” inhibited tumor growth and prolonged survival, via inducing apoptosis and down-regulation of MMP2 and VEGF, which indicated its potential use in patients with advanced HCC.

Anzeige

Bonham M, Arnold H, Montgomery B, Nelson PS (2002) Molecular effects of the herbal compound PC-SPES: identification of activity pathways in prostate carcinoma. Cancer Res 62:3920–3924PubMed

Carmeliet P (2005) Angiogenesis in life, disease, medicine. Nature 438:932–936. doi:10.1038/nature04478 PubMedCrossRef

Chang JY, Chang CY, Kuo CC, Chen LT, Wein YS, Kuo YH (2004) Salvinal, a novel microtubule inhibitor isolated from Salvia miltiorrhizae bunge (Danshen), with antimitotic activity in multidrug-sensitive and -resistant human tumor cells. Mol Pharmacol 65:77–84. doi:10.1124/mol.65.1.77 PubMedCrossRef

Cheng YL, Chang WL, Lee SC, Liu YG, Chen CJ, Lin SZ, Tsai NM, Yu DS, Yen CY, Harn HJ (2004) Acetone extract of Angelica sinensis inhibits proliferation of human cancer cells via inducing cell cycle arrest and apoptosis. Life Sci 75:1579–1594. doi:10.1016/j.lfs.2004.03.009 PubMedCrossRef

Guba M, von Breitenbuch P, Steinbauer M, Koehl G, Flegel S, Hornung M, Bruns CJ, Zuelke C, Farkas S, Anthuber M, Jauch KW, Geissler EK (2002) Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med 8:128–135. doi:10.1038/nm0202-128 PubMedCrossRef

Ho PK, Hawkins CJ (2005) Mammalian initiator apoptotic caspases. FEBS J 272:5436–5453. doi:10.1111/j.1742-4658.2005.04966.x PubMedCrossRef

Hong JH, Ahn KS, Bae E, Jeon SS, Choi HY (2006) The effects of curcumin on the invasiveness of prostate cancer in vitro and in vivo. Prostate Cancer Prostatic Dis 9:147–152. doi:10.1038/sj.pcan.4500856 PubMedCrossRef

Jiang C, Wang Z, Ganther H, Lu J (2001) Caspases as key executors of methyl selenium-induced apoptosis (anoikis) of DU-145 prostate cancer cells. Cancer Res 61:3062–3070PubMed

Jiang C, Lee HJ, Li GX, Guo J, Malewicz B, Zhao Y, Lee EO, Lee JH, Kim MS, Kim SH, Lu J (2006) Potent antiandrogen and androgen receptor activities of an angelica gigas—containing herbal formulation: identification of decursin as a novel and active compound with implications for prevention and treatment of prostate cancer. Cancer Res 66:453–463. doi:10.1158/0008-5472.CAN-05-1865 PubMedCrossRef

Kao ST, Yeh CC, Hsieh CC, Yang MD, Lee MR, Liu HS, Lin JG (2001) The Chinese medicine Bu-Zhong-Yi-Qi-Tang inhibited proliferation of hepatoma cell lines by inducing apoptosis via G0/G1 arrest. Life Sci 69:1485–1496. doi:10.1016/S0024-3205(01)01226-7 PubMedCrossRef

Kunnumakkara AB, Guha S, Krishnan S, Diagaradjane P, Gelovani J, Aggarwal BB (2007) Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res 67:3853–3861. doi:10.1158/0008-5472.CAN-06-4257 PubMedCrossRef

Lee SM, Li ML, Tse YC, Leung SC, Lee MM, Tsui SK, Fung KP, Lee CY, Way MM (2002) Paeoniae Radix, a Chinese herbal extract, inhibits hepatoma cell growth by inducing apoptosis in a p53 independent pathway. Life Sci 71:2267–2277. doi:10.1016/S0024-3205(02)01962-8 PubMedCrossRef

Lee HJ, Lee EO, Rhee YH, Ahn KS, Li GX, Jiang G, Lu J, Kim SH (2006) An oriental herbal cocktail, ka-mi-kae-kyuk-tang, exerts anti-cancer activities by targeting angiogenesis, apoptosis and metastasis. Carcinogenesis 27:2455–2463. doi:10.1093/carcin/bgl104 PubMedCrossRef

Li Y, Tang ZY, Ye SL, Liu YK, Chen J, Xue Q, Chen J, Gao DM, Bao WH (2001) Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol 7:630–636PubMed

Li M, Zhang Z, Hill DL, Wang H, Zhang R (2007) Curcumin, a dietary component, has anticancer, chemosensitization, and radiosensitization effects by down-regulating the MDM2 oncogene through the PI3 K/mTOR/ETS2 pathway. Cancer Res 67:1988–1996. doi:10.1158/0008-5472.CAN-06-3066 PubMedCrossRef

Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108PubMedCrossRef

Singh RP, Agarwal R (2006) Mechanisms of action of novel agents for prostate cancer chemoprevention. Endocr Relat Cancer 13:751–778. doi:10.1677/erc.1.01126 PubMedCrossRef

Siwik DA, Chang DL, Colucci WS (2000) Interleukin-1beta and tumor necrosis factor-alpha decrease collagen synthesis and increase matrix metalloproteinase activity in cardiac fibroblasts in vitro. Circ Res 86:1259–1265PubMed

Skehan P, Storeng R, Scudiero D, Monks A, McManhon J, Vistica D, Warren JT, Bokesch H, Kenney S, Boyd MR (1990) New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst 82:1107–1112. doi:10.1093/jnci/82.13.1107 PubMedCrossRef

Steeg PS (2006) Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12:895–904. doi:10.1038/nm1469 PubMedCrossRef

Sun FX, Tang ZY, Liu KD, Ye SL, Xue Q, Gao DM, Ma ZC (1996) Establishment of a metastatic model of human hepatocellular carcinoma in nude mice via orthotopic implantation of histologically intact tissues. Int J Cancer 66:239–243. doi:10.1002/(SICI)1097-0215(19960410)66:2<239::AID-IJC17>3.0.CO;2-7 PubMedCrossRef

Sung HJ, Choi SM, Yoon Y, An KS (1999) Tanshinone IIA, an ingredient of Salvia miltiorrhiza BUNGE, induces apoptosis in human leukemia cell lines through the activation of caspase-3. Exp Mol Med 31:174–178PubMed

Taichman RS, Loberg RD, Mehra R, Pienta KJ (2007) The evolving biology and treatment of prostate cancer. J Clin Invest 117:2351–2361. doi:10.1172/JCI31791 PubMedCrossRef

Tamvakopoulos C, Dimas K, Sofianos ZD, Hatziantoniou S, Han Z, Liu ZL, Wyche JH, Pantazis P (2007) Metabolism and anticancer activity of the curcumin analogue, dimethoxycurcumin. Clin Cancer Res 13:1269–1277. doi:10.1158/1078-0432.CCR-06-1839 PubMedCrossRef

Tang ZY, Ye SL, Liu YK, Qin LX, Sun HC, Ye QH, Wang L, Zhou J, Qiu SJ, Li Y, Ji JN, Liu H, Xia JL, Wu ZQ, Fan J, Ma ZC, Zhou XD, Lin ZY, Liu KD (2004) A decade’s studies on metastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol 130:187–196. doi:10.1007/s00432-003-0511-1 PubMedCrossRef

Tian J, Tang ZY, Ye SL, Liu YK, Lin ZY, Chen J, Xue Q (1999) New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. Br J Cancer 81:814–821. doi:10.1038/sj.bjc.6690769 PubMedCrossRef

Tsai NM, Lin SZ, Lee CC, Chen SP, Su HC, Chang WL, Harn HJ (2005) The antitumor effects of Angelica sinensis on malignant brain tumor in vitro and in vivo. Clin Cancer Res 11:3475–3484. doi:10.1158/1078-0432.CCR-04-1827 PubMedCrossRef

Wang L, Tang ZY, Qin LX, Wu XF, Sun HC, Xue Q, Ye SL (2000) High-dose and long-term therapy with interferon-alfa inhibits tumor growth and recurrence in nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential. Hepatology 32:43–48. doi:10.1053/jhep.2000.8525 PubMedCrossRef

Wang X, Wei Y, Yuan S, Liu G, Lu Y, Zhang J, Wang W (2005) Potential anticancer activity of tanshinone IIA against human breast cancer. Int J Cancer 116:799–807. doi:10.1002/ijc.20880 PubMedCrossRef

Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma. N Engl J Med 324:1–8PubMed

Yano H, Mizoguchi A, Fukuda K, Haramaki M, Ogasawara S, Momosaki S, Kojiro M (1994) The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1phase. Cancer Res 54:448–454PubMed

Ye QH, Qin LX, Forgues M, He P, Kim JW, Peng AC, Simon R, Li Y, Robles AI, Chen Y, Ma ZC, Wu ZQ, Ye SL, Liu YK, Tang ZY, Wang XW (2003) Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med 9:416–423. doi:10.1038/nm843 PubMedCrossRef

Yim D, Singh RP, Agarwal C, Lee S, Chi H, Agarwal R (2005) A novel anticancer agent, decursin, induces G1 arrest and apoptosis in human prostate carcinoma cells. Cancer Res 65:1035–1044. doi:10.1158/0008-5472.CAN-04-1740 PubMedCrossRef

Yuan SL, Huang RM, Wang XJ, Song Y, Huang GQ (1998) Reversing effect of tanshinone on malignant phenotypes of human hepatocarcinoma cell line. World J Gastroenterol 4:317–319PubMed

Yuan SL, Wei YQ, Wang XJ, Xiao F, Li SF, Zhang J (2004) Growth inhibition and apoptosis induction of tanshinone II-A on human hepatocellular carcinoma cells. World J Gastroenterol 10:2024–2028PubMed

Yue PY, Wong DY, Wu PK, Leung PY, Mak NK, Yeung HW, Liu L, Cai Z, Jiang ZH, Fan TP, Wong RN (2006) The angiosuppressive effects of 20(R)-ginsenoside Rg3. Biochem Pharmacol 72:437–445. doi:10.1016/j.bcp.2006.04.034 PubMedCrossRef

Zhang T, Sun HC, Xu Y, Zhang KZ, Wang L, Qin LX, Wu WZ, Liu YK, Ye SL, Tang ZY (2005) Overexpression of platelet-derived growth factor receptor-α in endothelial cells of hepatocellular carcinoma associated with high metastatic potential. Clin Cancer Res 11:8557–8563. doi:10.1158/1078-0432.CCR-05-0944 PubMedCrossRef

Zhang YH, Gu JF, Zhao LL, He LF, Qian WB, Wang JH, Wang YG, Qian QJ, Qian C, Wu J, Liu XY (2006) Complete elimination of colorectal tumor xenograft by combined manganese superoxide dismutase with tumor necrosis factor-related apoptosis-inducing ligand gene virotherapy. Cancer Res 66:4291–4298. doi:10.1158/0008-5472.CAN-05-1834 PubMedCrossRef

Zhou J, Tang ZY, Fan J, Wu ZQ, Ji Y, Xiao YS, Li XM, Sun QM, Liu YK, Ye SL (2003) Capecitabine inhibits postoperative recurrence and metastasis after liver cancer resection in nude mice with relation to the expression of platelet-derived endothelial cell growth factor. Clin Cancer Res 9:6030–6037PubMed

Titel: Herbal extract “Songyou Yin” inhibits tumor growth and prolongs survival in nude mice bearing human hepatocellular carcinoma xenograft with high metastatic potential
verfasst von: Xiu-Yan Huang
Lu Wang
Zi-Li Huang
Qi Zheng
Qi-Song Li
Zhao-You Tang
Publikationsdatum: 01.09.2009
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 9/2009
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-009-0566-8

Anzeige

Neu im Fachgebiet Onkologie

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Erhöhte Mortalität bei postpartalem Brustkrebs

07.05.2024 Mammakarzinom Nachrichten

Auch für Trägerinnen von BRCA-Varianten gilt: Erkranken sie fünf bis zehn Jahre nach der letzten Schwangerschaft an Brustkrebs, ist das Sterberisiko besonders hoch.

Hypertherme Chemotherapie bietet Chance auf Blasenerhalt

07.05.2024 Harnblasenkarzinom Nachrichten

Eine hypertherme intravesikale Chemotherapie mit Mitomycin kann für Patienten mit hochriskantem nicht muskelinvasivem Blasenkrebs eine Alternative zur radikalen Zystektomie darstellen. Kölner Urologen berichten über ihre Erfahrungen.

Ein Drittel der jungen Ärztinnen und Ärzte erwägt abzuwandern

07.05.2024 Klinik aktuell Nachrichten

Extreme Arbeitsverdichtung und kaum Supervision: Dr. Andrea Martini, Sprecherin des Bündnisses Junge Ärztinnen und Ärzte (BJÄ) über den Frust des ärztlichen Nachwuchses und die Vorteile des Rucksack-Modells.