Investigational New Drugs

, Volume 24, Issue 3, pp 181–187 | Cite as

Suppression of primary breast, colon, gastric and bladder cancers cell growth in vitro by CKBM, a natural product

  • Wei Zhang
  • Edgar S. L. LiuEmail author
  • Jun Fu
  • Hai-Mei Tian
  • Ying-Jye Wu
  • Shiu-Fun Pang
Preclinical Studies


CKBM is a product composed of natural ingredients and had been shown to possess certain anti-cancer effects in vitro and in vivo. The aim of the present study is to analyze the chemosensitivity in the treatment of primary colon, breast, gastric and bladder cancer cells by CKBM. A total of 77 patients with cancers of breast, colon, stomach or bladder were included in the present study. Primary cancer cells were isolated from the surgical removed tumors and treated with various dosages of CKBM for 5 days. ATP is then extracted and measured by luminescence assay. CKBM treatment inhibited primary colon, breast, gastric and bladder cancer growth dose-dependently. The IC values were smaller from tumor cells at early stages, when compared with the ones at later stages. The present study strongly indicated that CKBM exerted cytotoxic effect on primary cancer cells.

Key Words

chemosensitivity colon cancer gastric cancer breast cancer bladder cancer 


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  1. 1.
    Whitehouse PA, Knight LA, Di Nicolantonio F, Mercer SJ, Sharma S, Cree IA: Portsmouth colorectal cancer multidisciplinary team: Heterogeneity of chemosensitivity of colorectal adenocarcinoma determined by a modified ex vivo ATP-tumor chemosensitivity assay (ATP-TCA). Anticancer Drugs 14: 369–375, 2003CrossRefPubMedGoogle Scholar
  2. 2.
    Kurbacher CM, Cree IA, Bruckner HW, Brenne U, Kurbacher JA, Muller K, Ackermann T, Gilster TJ, Wilhelm LM, Engel H, Mallmann PK, Andreotti PE: Use of an ex vivo ATP luminescence assay to direct chemotherapy for recurrent ovarian cancer. Anticancer Drugs 9: 51–57, 1998PubMedGoogle Scholar
  3. 3.
    Xu GW, Sun ZT, Forrester K, Wang XW, Coursen J, Harris CC: Tissue-specific growth suppression and chemosensitivity promotion in human hepatocellular carcinoma cells by retroviral-mediated transfer of the wild-type p53 gene. Hepatology 24: 1264–1268, 1996PubMedGoogle Scholar
  4. 4.
    Shin VY, So WHL, Liu ESL, Wu YJ, Pang SF, Cho CH: Anti-tumorigenic and pro-apoptotic effects of CKBM on gastric cancer growth in nude mice. Int J Med Sci 1: 137–145, 2004PubMedGoogle Scholar
  5. 5.
    Chan JY, Cheung JY, Luk SC, Wu YJ, Pang SF, Fung KP: Anti-cancer and pro-apoptotic effects of an herbal medicine and Saccharomyces cerevisiae product (CKBM) on human hepatocellular carcinoma hep G2 cells in vitro and in vivo. Immunopharmacol Immunotoxicol (accepted)Google Scholar
  6. 6.
    Chan BP, Yuen WF, Lee WH, Wong SN, Chung TY, Wu YJ, Pang SF: Immunomodulating effects of CKBM on the cytokine production in peripheral blood mononuclear cells (PBMCs) from healthy volunteers. Immunopharmacol Immunotoxicol 26: 177–192, 2004CrossRefPubMedGoogle Scholar
  7. 7.
    Andreotti PE, Cree IA, Kurbacher CM, Hartmann DM, Linder D, Harel G, Gleiberman I, Caruso PA, Ricks SH, Untch M, Sartori C, Bruckner HW: Chemosensitivity testing of human tumors using a microplate adenosine triphosphate luminescence assay: Clinical correlation for cisplatin resistance of ovarian carcinoma. Cancer Res 55: 5276–5282, 1995PubMedGoogle Scholar
  8. 8.
    Kuzmits R, Aiginger P, Muller MM, Steurer G, Linkesch W: Assessment of the sensitivity of leukaemic cells to cytotoxic drugs by bioluminescence measurement of ATP in cultured cells. Clin Sci (Lond) 71: 81–88, 1986Google Scholar
  9. 9.
    Sevin BU, Peng ZL, Perras JP, Ganjei P, Penalver M, Averette HE: Application of an ATP-bioluminescence assay in human tumor chemosensitivity testing. Gynecol Oncol 31: 191–204, 1988CrossRefPubMedGoogle Scholar
  10. 10.
    Maehara Y, Anai H, Tamada R, Sugimachi K: The ATP assay is more sensitive than the succinate dehydrogenase inhibition test for predicting cell viability. Eur J Cancer Clin Oncol 23: 273–276, 1987CrossRefPubMedGoogle Scholar
  11. 11.
    Tokunaka K, Ohno N, Adachi Y, Miura NN, Yadomae T: Application of Candida solubilized cell wall beta-glucan in antitumor immunotherapy against P815 mastocytoma in mice. Int Immunopharmacol 2: 59–67, 2002CrossRefPubMedGoogle Scholar
  12. 12.
    Ross GD, Vetvicka V, Yan J, Xia Y, Vetvickova J: Therapeutic intervention with complement and beta-glucan in cancer. Immunopharmacology 42: 61–74, 1999.CrossRefPubMedGoogle Scholar
  13. 13.
    Liu WK, Xu SX, Che CT: Anti-proliferative effect of ginseng saponins on human prostate cancer cell line. Life Sci 67: 1297–1306, 2000CrossRefPubMedGoogle Scholar
  14. 14.
    Oh M, Choi YH, Choi S, Chung H, Kim K, Kim SI, Kim DK, Kim ND: Anti-proliferating effects of ginsenoside Rh2 on MCF-7 human breast cancer cells. Int J Oncol 14: 869–875, 1999PubMedGoogle Scholar
  15. 15.
    Hakkak R, Korourian S, Ronis MJ, Johnston JM, Badger TM: Soy protein isolate consumption protects against azoxymethane-induced colon tumors in male rats. Cancer Lett 166: 27–32, 2001CrossRefPubMedGoogle Scholar
  16. 16.
    Hikosaka A, Asamoto M, Hokaiwado N, Kato K, Kuzutani K, Kohri K, Shirai T: Inhibitory effects of soy isoflavones on rat prostate carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Carcinogenesis 25: 381–387, 2004CrossRefPubMedGoogle Scholar
  17. 17.
    Gong L, Li Y, Nedeljkovic-Kurepa A, Sarkar FH: Inactivation of NF-kappaB by genistein is mediated via Akt signaling pathway in breast cancer cells. Oncogene 22: 4702–4709, 2003CrossRefPubMedGoogle Scholar
  18. 18.
    Huynh H, Nguyen TT, Chan E, Tran E: Inhibition of ErbB-2 and ErbB-3 expression by quercetin prevents transforming growth factor alpha (TGF-alpha)- and epidermal growth factor (EGF)-induced human PC-3 prostate cancer cell proliferation. Int J Oncol 23: 821–829, 2003PubMedGoogle Scholar
  19. 19.
    Lung HL, Ip WK, Chen ZY, Mak NK, Leung KN: Comparative study of the growth-inhibitory and apoptosis-inducing activities of black tea theaflavins and green tea catechin on murine myeloid leukemia cells. Int J Mol Med 13: 465–471, 2004PubMedGoogle Scholar
  20. 20.
    Shen SC, Chen YC, Hsu FL, Lee WR: Differential apoptosis-inducing effect of quercetin and its glycosides in human promyeloleukemic HL-60 cells by alternative activation of the caspase 3 cascade. J Cell Biochem 89: 1044–1055, 2003CrossRefPubMedGoogle Scholar
  21. 21.
    Shidoji Y, Ogawa H: Natural occurrence of cancer-preventive geranylgeranoic acid in medicinal herbs. J Lipid Res 45: 1092–1103, 2004CrossRefPubMedGoogle Scholar
  22. 22.
    Yasukawa K, Ikeya Y, Mitsuhashi H, Iwasaki M, Aburada M, Nakagawa S, Takeuchi M, Takido M: Gomisin A inhibits tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin. Oncology 49: 68–71, 1992PubMedCrossRefGoogle Scholar
  23. 23.
    Chen J, Tan KP, Ward WE, Thompson LU: Exposure to flaxseed or its purified lignan during suckling inhibits chemically induced rat mammary tumorigenesis. Exp Biol Med (Maywood) 228: 951–958, 2003Google Scholar
  24. 24.
    Watanabe S, Kitade Y, Masaki T, Nishioka M, Satoh K, Nishino H: Effects of lycopene and Sho-saiko-to on hepatocarcinogenesis in a rat model of spontaneous liver cancer. Nutr Cancer 39: 96–101, 2001CrossRefPubMedGoogle Scholar
  25. 25.
    Mercer SJ, Somers SS, Knight LA, Whitehouse PA, Sharma S, Di Nicolantonio F, Glaysher S, Toh S, Cree IA: Portsmouth Upper GI Cancer Multi-Disciplinary Team: Heterogeneity of chemosensitivity of esophageal and gastric carcinoma. Anticancer Drugs 14: 397–403, 2003CrossRefPubMedGoogle Scholar
  26. 26.
    Zunino F, Perego P, Pilotti S, Pratesi G, Supino R, Arcamone F: Role of apoptotic response in cellular resistance to cytotoxic agents. Pharmacol Ther 76: 177–185, 1997CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2005

Authors and Affiliations

  • Wei Zhang
    • 1
  • Edgar S. L. Liu
    • 2
    • 3
    Email author
  • Jun Fu
    • 1
  • Hai-Mei Tian
    • 1
  • Ying-Jye Wu
    • 2
  • Shiu-Fun Pang
    • 2
  1. 1.Detection Center of Tumor Biology, Cancer Institute & HospitalChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijing
  2. 2.CK Life Sciences LimitedN.T.Hong Kong
  3. 3.CK Life Sciences LimitedN.T.Hong Kong

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