In vitro and in vivo anti-tumoral effect of curcumin against melanoma cells
Johann Odot
Laboratoire de Biologie Cellulaire et Moléculaire, EA 3306 U.F.R Sciences, Reims, France
Search for more papers by this authorCorresponding Author
Philippe Albert
Laboratoire de Biologie Cellulaire et Moléculaire, EA 3306 U.F.R Sciences, Reims, France
Fax: +33-03-26-91-32-82
Laboratoire de Biologie Cellulaire et Moléculaire, UFR des Sciences, BP 1039, 51687 Reims Cedex 2, FranceSearch for more papers by this authorAnnie Carlier
Laboratoire de Biologie Cellulaire et Moléculaire, EA 3306 U.F.R Sciences, Reims, France
Search for more papers by this authorMichel Tarpin
Laboratoire de Biologie Cellulaire et Moléculaire, EA 3306 U.F.R Sciences, Reims, France
Search for more papers by this authorJérôme Devy
Laboratoire de Biochimie et Biologie Moléculaire, EA 3306, U.F.R. Pharmacie, IFR 53 Biomolécules, Reims, France
Search for more papers by this authorClaudie Madoulet
Laboratoire de Biochimie et Biologie Moléculaire, EA 3306, U.F.R. Pharmacie, IFR 53 Biomolécules, Reims, France
Search for more papers by this authorJohann Odot
Laboratoire de Biologie Cellulaire et Moléculaire, EA 3306 U.F.R Sciences, Reims, France
Search for more papers by this authorCorresponding Author
Philippe Albert
Laboratoire de Biologie Cellulaire et Moléculaire, EA 3306 U.F.R Sciences, Reims, France
Fax: +33-03-26-91-32-82
Laboratoire de Biologie Cellulaire et Moléculaire, UFR des Sciences, BP 1039, 51687 Reims Cedex 2, FranceSearch for more papers by this authorAnnie Carlier
Laboratoire de Biologie Cellulaire et Moléculaire, EA 3306 U.F.R Sciences, Reims, France
Search for more papers by this authorMichel Tarpin
Laboratoire de Biologie Cellulaire et Moléculaire, EA 3306 U.F.R Sciences, Reims, France
Search for more papers by this authorJérôme Devy
Laboratoire de Biochimie et Biologie Moléculaire, EA 3306, U.F.R. Pharmacie, IFR 53 Biomolécules, Reims, France
Search for more papers by this authorClaudie Madoulet
Laboratoire de Biochimie et Biologie Moléculaire, EA 3306, U.F.R. Pharmacie, IFR 53 Biomolécules, Reims, France
Search for more papers by this authorAbstract
Curcumin, the active ingredient from the spice turmeric (Curcuma longa Linn), is known to be an anti-oxidant and an anti-inflammatory agent. It has been demonstrated recently to possess anti-angiogenic effects and pro-apoptotic activities against Ehrlich ascites tumor cells. In the current study, curcumin was found to be cytotoxic in vitro for B16-R melanoma cells resistant to doxorubicin either cultivated as monolayers or grown in three-dimensional (3-D) cultures (spheroids). We have demonstrated that the cytotoxic effect observed in the 2 culture types can be related to the induction of programmed cell death. In our in vivo studies, we examined the effectiveness of a prophylactic immune preparation of soluble proteins from B16-R cells, or a treatment with curcumin as soon as tumoral appearance, alone or in combination, on the murine melanoma B16-R. The combination treatment resulted in substantial inhibition of growth of B16-R melanoma, whereas each treatment by itself showed little effect. Moreover, animals receiving the combination therapy exhibited an enhancement of their humoral anti-soluble B16-R protein immune response and a significant increase in their median survival time (>82.8% vs. 48.6% and 45.7% respectively for the immunized group and the curcumin-treated group). Our study shows that curcumin may provide a valuable tool for the development of a therapeutic combination against the melanoma. © 2004 Wiley-Liss, Inc.
REFERENCES
- 1 Colin M, Madoulet C, Warren L, Jardillier JC. Alterations of vinblastine influx in multidrug resistant lymphoblastic leukemic CEM cells. Anticancer Res 1996; 16: 407–12.
- 2 Colin M, Madoulet C, Bobichon H, Kaplan F, Warren L, Jardillier JC. Evidence for reduced drug influx in multidrug CEM cells by a fluorescent dye. Int J Oncol 1997; 11: 377–82.
- 3 Endicott JA, Ling V. The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu Rev Biochem 1989; 58: 137–71.
- 4 Gottesman MM, Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem 1993; 62: 385–427.
- 5 Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, Mulligan RC. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 1993; 90: 3539–43.
- 6 Soiffer R, Lynch T, Mihm M, Jung K, Rhuda C, Schmollinger JC, Hodi FS, Liebster L, Lam P, Mentzer S, Singer S, Tanabe KK, et al. Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma. Proc Natl Acad Sci USA 1998; 95: 13141–6.
- 7 Van Elsas A, Hurwitz AA, Allison JP. Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J Exp Med 1999; 190: 355–66.
- 8 Van Elsas A, Sutmuller RPM, Hurwitz AA, Ziskin J, Villasenor J, Medema JP, Overmijk WW, Restifo NP, Melief CJM, Offringa R, Allison JP. Elucidating the autoimmune and antitumor effector mechanisms of a treatment base on cytotoxic T lymphocyte antigen-4 blockade in combination with a B16 melanoma vaccine: comparison of prophylaxis and therapy. J Exp Med 2001; 194: 481–9.
- 9 Berd D, Sato T, Mastrangelo MJ. Effect of the dose and composition of an autologous hapten-modified melanoma vaccine on the development of delayed-type hypersensitivity responses. Cancer Immunol Immunother 2002; 51: 320–6.
- 10 Vaishampayan U, Abrams J, Darrah D, Jones V, Mitchell MS. Active immunotherapy of metastatic melanoma with allogeneic melanoma lysates and interferon α. Clin Cancer Res 2002; 8: 3696–701.
- 11 Asavaroengchai W, Kotera Y, Mulé JJ. Tumor lysate-pulsed dendritic cells can elicit an effective antitumor immune response during early lymphoid recovery. Proc Natl Acad Sci USA 2002; 99: 931–6.
- 12 Fields RC, Schimizu K, Mulé JJ. Murine dendritic cells pulsed with whole tumor lysates mediate potent antitumor immune responses in vitro and in vivo. Proc Natl Acad Sci USA 1998; 95: 9482–7.
- 13 Tanaka M, Kaneda Y, Fujii S, Amano T, Hashimoto K, Huang SKS, Hoon DSB. Induction of a systemic immune response by a polyvalent melanoma-associated antigen DNA vaccine for prevention and treatment of malignant melanoma. Mol Therapy 2002; 5: 291–9.
- 14 Tang D, DeVit M, Johnston A. Genetic immunization is a simple method for eliciting an immune response. Nature 1992; 356: 152–3.
- 15 Gurunathan S, Klinman DM, Seder RA. DNA vaccines: immunology, application and optimization. Annu Rev Immunol 2000; 18: 927–74.
- 16
Marchand M,
Van Baren N,
Weynants P.
Tumor regression observed in patients with metastatic melanoma treated with an antigenic peptide encodes by gene MAGE-3 and presented by HLA-A1.
Int J Cancer
1999;
80:
219–30.
10.1002/(SICI)1097-0215(19990118)80:2<219::AID-IJC10>3.0.CO;2-S CAS PubMed Web of Science® Google Scholar
- 17 Cormier JN, Salgaller ML, Prevette T. Enhancement of cellular immunity in melanoma patients immunized with a peptide from MART-1/Melan A. Cancer J Sci Am 1997; 3: 37–44.
- 18
Jager E,
Maeurer M,
Hohn H.
Clonal expression of Melan A-specific cytotoxic T lymphocytes in a melanoma patient responding to continued immunization with melanoma-associated peptides.
Int J Cancer
2000;
86:
538–547
10.1002/(SICI)1097-0215(20000515)86:4<538::AID-IJC16>3.0.CO;2-G CAS PubMed Web of Science® Google Scholar
- 19 Govindaraja VS. Turmeric: chemistry, technology, and quality. Crit Rev Food Sci Nutr 1980; 12: 199.
- 20 Nandkarni KM. Curcuma longa. Bombay: Popular Prakashan, 1976.
- 21 Amon HP, Wahl MA. Pharmacology of Curcuma longa. Plant Med 1991; 57: 1–7.
- 22 Gururaj AE, Belakavadi M, Venkatesh DA, Marmé D, Salimath BP. Molecular mechanisms of anti-angiogenic effect of curcumin. Biochem Biophys Res Com 2002; 297: 934–42.
- 23 Lu YP, Chang RL, Lou YR, Huang MT, Newmark HL, Reuhl K, Conney AH. Effect of curcumin on 12-o-tetradecanoyl-phorbol-13-acetate- and ultraviolet B light-induced expression of c-jun and c-fos in JB6 cells and in mouse epidermis. Carcinogenesis 1994; 15: 2363–70.
- 24 Singh S, Aggarwal BB. Activation of transcription factor NF-κB is suppresses by curcumin. J Biol Chem 1995; 270: 24995–5000.
- 25 Rao CV, Simi B, Reddy BS. Inhibition by dietary curcumin of azoxymethanol-induced ornithine decarboxylase, tyrosine protein kinase, arachidonic acid metabolism and aberrant crypt foci formation in the rat colon. Carcinogenesis 1993; 14: 2219–25.
- 26 Huang MT, Ma W, Lu YP, Chang RL, Fisher C, Manchand PS, Newmark HL, Conney AH. Effects of curcumin, demethoxycurcumin, bis demethoxycurcumin, and tetrahydrocurcumin on 12-0-tetradecanoylphorbol-13acetate-induced tumor promotion. Carcinogenesis 1995; 16: 2493–7.
- 27 Huang MT, Deschner EE, Newmark HL, Wang ZY, Ferraro TA, Conney AH. Effect of dietary curcumin and ascorbyl palmitate on azoxymethanol-induced colonic epithelial cell proliferation and focal areas of dysplasia. Cancer Lett 1992; 64: 117–21.
- 28 Kelloff GJ, Crowell JA, Hawk ET, Steele VE, Lubet RA, Bonne CW, Covey JM, Doody LA, Omenn GS, Greenwald P, Hong WK, Parkinson DR, et al. Strategy and planning for chemopreventive drug development: clinical development plans II. J Cell Biochem 1996; 26: 54–71.
- 29 Pal S, Choudhuri T, Chattopadhyay S, Bhattacharya A, Datta GK, Das T, Sa G. Mechanisms of curcumin-induced apoptosis of Ehrlich's ascites carcinoma cells. Biochem Biophys Res Com 2001; 288: 658–65.
- 30 Mariani M, Supino R. Morphological alterations induced by doxorubicin in B16 melanoma cells. Cancer Lett 1990; 51: 209–12.
- 31 Sambrook J, Fritsch EF, Maniatis T. Molecular cloning: a laboratory manual, 2nd ed. New York: Cold Spring Harbor, 1989. 458–9.
- 32 Jiang MC, Yang-Yen HF, Yen JJ, Lin JK. Curcumin induces apoptosis in immortalized NIH3T3 and malignant cancer cell lines. Cancer 1996; 26: 111–20.
- 33 Rao CV, Rivenson A, Simi B, Reddy BS. Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound. Cancer Res 1995; 55: 259–66.
- 34 Sutherland RM. Cell and environment interaction in tumor micro regions: the multicell spheroid model. Science 1988; 240: 177–84.
- 35 Hanif R, Qiao L, Shiff SJ, Rigas B. Curcumin, a natural plant phenolic food additive, inhibits cell proliferation and induces cell cycle changes in colon adenocarcinoma cell lines by a prostaglandin-independent pathway. J Lab Clin Med 1997; 130: 576–84.
- 36 Ramachandran C, You W. Differential sensitivity of human mammary epithelial and breast carcinoma cell line to curcumin. Breast Cancer Res Treat 1999; 54: 269–78.
- 37 Kuo M, Huang TS, Lin JK. Curcumin, an antioxidant and anti-tumor promoter, induces apoptosis in human leukemia cells. Biochim Biophys Acta 1996; 1317: 95–100.
- 38 Sikora E, Bielak-Zmijewska A, Piwocka K, Skierski J, Radziszewska E. Inhibition of proliferation and apoptosis of human and rat T lymphocytes by curcumin, a curry pigment. Biochem Pharmacol 1997; 54: 899–907.
- 39 Somasundaram S, Edmund NA, Moore DT, Small GW, Shi YY, Orlowski RZ. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res 2002; 62: 3868–75.
- 40 Samaha HS, Kellof Gj, Steele V, Rao CV, Reddy BS. Modulation of apoptosis by sulindac, curcumin, phenylethyl-3-methylcaffeate, and 6-phenylhexyl isothiocyanate: apoptotic index as a biomarker in colon cancer chemoprevention and promotion. Cancer Res 1997; 57: 1301–5.
- 41 Bush JA, Cheung KJJ Jr, Li G. Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53. Exp Cell Res 2001; 271: 305–14.
- 42 Limtrakul P, Lipigorngoson S, Namwong O, Apisariyakul A, Dunn FW. Inhibitory effect of dietary curcumin on skin carcinogenesis in mice. Cancer Lett 1997; 116: 197–203.
- 43 Menon LG, Kuttan R, Kuttan G. Inhibition of lung metastasis in mice induced by B16F10 melanoma cells by polyphenolic compounds. Cancer Lett 1995; 95: 221–5.
- 44 Menon LG, Kuttan R, Kuttan G. Anti-metastatic activity of curcumin and catechin. Cancer Lett 1999; 95: 159–65.
- 45 Caltagirone S, Rossi C, Poggi A, Ranelletti FO, Giorgio Natali P, Brunetti M, Aiello FB, Piantelli M. Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. Int J Cancer 2000; 87: 595–600.
- 46 Bille N, Larsen JC, Hansen EV, Wurtzen G. Subchronic oral toxicity of turmeric oleoresin in pigs. Food Chem Toxicol 1985; 23: 967–73.
- 47 Cheng AL, Hsu CH, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, YU HS, Jee SH et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 2001; 21: 2895–900.
- 48 Scheffer SR, Nave H, Korangy F, Scholte K, Pabst R, Jaffee EM, Manns MP, Greten TF. Apoptotic, but not necrotic tumor cell vaccines induce a potent immune response in vivo. Int J Cancer 2003; 103: 205–11.
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