Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-19T08:42:48.639Z Has data issue: false hasContentIssue false
  • English
  • Français

Energy-modulating vitamins – a new combinatorial therapy prevents cancer cachexia in rat mammary carcinoma

Published online by Cambridge University Press:  08 March 2007

Selvanathan Saravana Perumal ,
Palanivelu Shanthi  and
Panchanadham Sachdanandam
Selvanathan Saravana Perumal
Affiliation:
Department of Medical Biochemistry, University of Madras, Taramani Campus, Chennai 600 113, India
Palanivelu Shanthi
Affiliation:
Department of Pathology, Dr AL Mudaliar Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India
Panchanadham Sachdanandam*
Affiliation:
Department of Medical Biochemistry, University of Madras, Taramani Campus, Chennai 600 113, India
*
*Corresponding author: Dr P. Sachdanandam, fax +91 44 24926709, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Mitochondria are the major intracellular organelles producing ATP molecules via the electron transport chain. Cancer cells have a deviant energy metabolism, and a high rate of glycolysis is related to a high degree of dedifferentiation and proliferation. The overall net ATP production is diminished with cancer, which ultimately leads to cancer cachexia. The present study was designed to investigate the altered energy metabolism in cancer cells and to enhance ATP production in the normal host cell metabolism by enhancing the activities of mitochondrial enzymes, using energy-modulating vitamins, and thus prevent cancer cachexia. Female Sprague–Dawley rats were selected for the experimental study. Mammary carcinoma was induced by the oral administration of 7,12-dimethylbenz[a]anthracene (25 mg/kg body weight), and treatment was started by the oral administration of the energy-modulating vitamins riboflavin (45 mg/kg body weight per d), niacin (100 mg/kg body weight per d) and coenzyme Q10 (40 mg/kg body weight per d) for 28 d. Mitochondria were isolated from the mammary gland and liver of all four groups, and the Krebs cycle and oxidative phosphorylation enzymes were assayed. In mammary carcinoma-bearing animals, the activities of the Krebs cycle and oxidative phosphorylation enzymes were significantly decreased. These activities were restored to a greater extent in animals treated with energy-modulating vitamins. From these experimental results, one may hypothesize that the combination therapy of energy-modulating vitamins could be of major therapeutic value in breast cancer.

Keywords

Breast cancerEnergy-modulating vitaminsMitochondrial enzymesCancer cachexia
Type
Research Article
Information
British Journal of Nutrition , Volume 93 , Issue 6 , June 2005 , pp. 901 - 909
Copyright
Copyright © The Nutrition Society 2005

References

Baggetto, LG (1992) Deviant energetic metabolism of glycolytic cancer cells. Biochimie 74, 959–974.CrossRefGoogle ScholarPubMed
Baggetto, LG (1993) Role of mitochondria in carcinogenesis. Eur J Cancer 29, 156–159.CrossRefGoogle Scholar
Bayoumi, RA & Rosalki, SB (1976) Evaluation of methods of coenzyme activation of erythrocyte enzymes for detection of deficiency of vitamins B1, B2 and B6. Clin Chem 22, 327–335.Google Scholar
Bradlow, HL & Sepkovic, DW (2002) Diet and breast cancer. Ann NY Acad Sci 963, 247–267.Google Scholar
Burton, K (1956) A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 62, 315–323.CrossRefGoogle ScholarPubMed
Cervantes-Laurean, D, McElvaney, NG & Moss, J (1999) Niacin. In Modern Nutrition in Health and Disease, pp. 401–411 [Shils, ME, Olson, JA, Shike, M and Ross, AC, editors]. Baltimore, MD: Williams Wilkins.Google Scholar
Coper, H & Neubert, D (1964) Effect of NAD and other NAD analogues on the formation of NADPH and its transphosphorylation to ATP. Biochim Biophys Acta 82, 167–170.Google Scholar
Damle, SR, Talavdekar, RV & Panse, TB (1971) The studies on glycolytic enzymes in relation to cancer. II. Comparative study of phosphohexose-isomerase, aldolase, isocitric dehydrogenase, serum glutamic oxaloacetic and pyruvic transaminase, and alkaline phosphatase in liver. Ind J Cancer 8, 21–29.Google ScholarPubMed
DeWys, WD, Begg, C & Lavin, PT (1980) Prognostic effect of weight loss prior to chemotherapy in cancer patients. Am J Med 69, 491–497.CrossRefGoogle ScholarPubMed
Diamond, WJ, Cowden, WL & Goldberg, B (1997) An alternative medicine definitive guide to cancer. Tiburon Califormia: Future Medicine Publishing.Google Scholar
Dietzen, DJ & Davis, EJ (1993) Oxidation of pyruvate, malate, citrate, and cytosolic reducing equivalents by AS-30D hepatoma mitochondria. Arch Biochem Biophys 305, 91–102.Google Scholar
Dreizen, SMcCredie, KBKeating, MJ & Andersson, BS (1990) Nutritional deficiencies in patients receiving cancer chemotherapy. Postgrad Med 87, 163–167.CrossRefGoogle ScholarPubMed
Ernster, L (1977) Facts and ideas about the function of coenzyme Q10 in the mitochondria. In Biomedical and Clinical Aspects of Coenzyme Q, pp. 15–18 [Folkers, K and Yamamura, Y, editors]. Amsterdam: Elsevier.Google Scholar
Folkers, K, Brown, R, Judy, WV & Morita, M (1993) Survival of cancer patients on therapy with coenzyme Q10. Biochem Biophys Res Commun 192, 241–245.Google Scholar
Folkers, K, Osterborg, A, Nylander, M, Morita, M & Mellstedt, H (1997) Activities of vitamin Q10 in animal models and a serious deficiency in patients with cancer. Biochem Biophys Res Commun 234, 296–299.CrossRefGoogle Scholar
Golshani-Hebroni, SG & Bessman, SP (1997) Hexokinase binding to mitochondria: a basis for proliferative energy metabolism. J Bioenerg Biomemb 29, 331–338.CrossRefGoogle ScholarPubMed
Greenhouse, WV & Lehninger, AL (1977) Magnitude of malate-aspartate reduced nicotinamide adenine dinucleotide shuttle activity in intact respiring tumor cells. Cancer Res 37, 4173–4181.Google Scholar
Hennipman, A, Van Oirschot, BS, Smit, J, Rijsken, G & Stacil, GE (1988) Heterogenicity of glycolytic enzyme activity and isozyme composition of pyruvate kinase in breast cancer. Tumour Biol 9, 178–189.Google Scholar
Inculet, RI, Norton, JA, Nichoalds, GE, Maher, MM, White, DE & Brennan, MF (1987) Water-soluble vitamins in cancer patients on parenteral nutrition: a prospective study. JPEN J Parenter Enteral Nutr 11, 243–249.CrossRefGoogle ScholarPubMed
Jacobson, E (1993) Niacin deficiency and cancer in women. J Am Coll Nutr 12, 412–416.CrossRefGoogle ScholarPubMed
Jacobson, EL & Jacobson, MK (1993) A biomarker for the assessment of niacin nutriture as a potential preventive factor in carcinogenesis. J Int Med 233, 59–62.Google Scholar
Jacobson, EL, Shieh, WM & Huang, AC (1999) Mapping the role of NAD metabolism in prevention and treatment of carcinogenesis. Mol Cell Biochem 193, 69–74.CrossRefGoogle ScholarPubMed
Johnson, D & Lardy, H (1967) Isolation of liver or kidney mitochondria. Methods Enzymol 10, 94–96.CrossRefGoogle Scholar
Jolliet, P, Simon, N, Barre, J, Boukef, JY, Paniel, BJ & Tillement, JP (1998) Plasma co-enzyme Q10 concentration in breast cancer: prognosis and therapeutic consequence. Int J Clin Pharm Ther 36, 506–509.Google Scholar
Kensler, CJ, Sugiura, K, Young, NF, Halter, CR & Rhoads, CP (1941) Partial protection of rats by riboflavin with casein against liver cancer caused by dimethylaminoazobenzene. Science 93, 308–310.CrossRefGoogle ScholarPubMed
King, J (1965) Transferases. In Practical clinical enzymology, p. 263 [Van Nostrand, D, editor]. London NJ: Nostrand Company Ltd.Google Scholar
Koroshetz, WJ, Jenkins, BG, Rosen, BR & Beal, MF (1997) Energy metabolism defects in Huntington's disease and effects of coenzyme Q10. Ann Neurol 41, 160–165.Google Scholar
Le Bricon, T, Gugins, S, Cynober, L & Baracos, VE (1995) Negative impact of cancer chemotherapy on protein metabolism in healthy and tumor-bearing rats. Metabolism 44, 1340–1348.Google Scholar
Li, D, Zhang, W, Sahin, AA & Hittelman, WN (1999) DNA adducts in normal tissue adjacent to breast cancer: a review. Cancer Detect Prev 23, 454–462.CrossRefGoogle ScholarPubMed
Lin, CC, Lu, YP, Lou, YR, Ho, CT, Newmark, HMacDonald, CSingletary, KW & Huang, MT (2001) Inhibition by dietary dibenzoylmethane of mammary gland proliferation, formation of DMBA-DNA adducts in mammary glands, and mammary tumorigenesis in Sencar mice. Cancer Lett 168, 125–132.CrossRefGoogle ScholarPubMed
Lockwood, K, Moesgaard, S & Folkers, K (1994) Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10. Biochem Biophys Res Comm 199, 1504–1508.CrossRefGoogle ScholarPubMed
Lockwood, K, Moesgaard, S, Yamamoto, T & Folkers, K (1995) Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Commun 212, 172–177.CrossRefGoogle Scholar
Lowry, OH, Rosebrough, NJ, Farr, AL & Randall, RJ (1951) Protein measurement with folin-phenol reagent. J Biol Chem 193, 265–275.CrossRefGoogle ScholarPubMed
McCormick, DB (1999) Riboflavin. In Modern Nutrition in Health and Disease, pp. 391–399 [Shils, ME, Olson, JA, Shike, M and Ross, AC, editors]. Baltimore: Williams & Wilkins.Google Scholar
Mehler, AH, Kornberg, A, Grisolia, S & Ochoa, S (1948) The enzymatic mechanisms of oxidation reduction between malate or isocitrate and pyruvate. J Biol Chem 174, 961–977.Google Scholar
Minakami, S, Ringer, RL & Singer, TP (1962) Studies on respiratory chain linked dihydrodiphosphopyridine nucleotide dehydrogenase. J Biol Chem 237, 569–576.Google Scholar
Morita, M & Folkers, K (1993) A new method to determine the level of coenzyme Q10 in one drop of human blood for biomedical research. Biochem Biophys Res Commun 191, 950–995.Google Scholar
Mulligan, HD & Tisdale, MJ (1991) Metabolic substrate utilization by tumour and host tissues in cancer cachexia. Biochem J 277, 321–326.Google Scholar
Ogilvie, GK & Vail, DM (1996) Metabolic alterations and nutritional therapy for the veterinary cancer patient. In Clinical Veterinary Oncology, [Withrow, SJ and MacEwen, EG, editors]. Philadelphia: WB Saunders.Google Scholar
Pain, VM, Randall, DP & Garlick, PJ (1984) Protein synthesis in liver and skeletal muscle of mice bearing ascites tumour. Cancer Res 44, 1054–1057.Google Scholar
Palani, V, Senthilkumaran, RK & Govindasamy, S (1999) Biochemical evaluation of antitumour effect of Muthu Marunthu (a herbal formulation) on experimental fibrosarcoma in rats. Toxicol Pathol 12, 162–166.Google Scholar
Pangrekar, J, Krishnaswamy, K & Jagadeesan, V (1993) Effects of riboflavin deficiency and riboflavin administration on carcinogen-DNA binding. Chem Toxicol 31, 745–750.Google Scholar
Parlo, RA & Coleman, PS (1984) Enhanced rate of citrate export from cholesterol-rich hepatoma mitochondria. The truncated krebs cycle and other metabolic ramification of mitochondrial membrane cholesterol. J Biol Chem 259, 9997–10003.Google Scholar
Parry, DM & Pedersen, PL (1983) Intracellular localization and properties of particulate hexokinase in the Novikoof ascites tumour: evidence for an outer mitochondrial membrane location. J Biol Chem 258, 10904–10912.CrossRefGoogle Scholar
Pederson, PL (1978) Tumor mitochondria and the bioenergetics of cancer cells. Prog Exp Tumor Res 22, 190–274.Google Scholar
Powers, HJ (1999) Current knowledge concerning optimal nutrition status of riboflavin, niacin and pyridoxin. Proc Nutr Soc 58, 435–440.Google Scholar
Rajeswari, N, Ahuja, YR, Malini, U, Chandrashekar, S, Balakrishna, N, Rao, KV & Khar, A (2000) Risk assessment in first degree female relatives of breast cancer patients using the alkaline Comet assay. Carcinogenesis 21, 557–561.CrossRefGoogle ScholarPubMed
Rawal, UM, Patel, US, Rao, GN & Desai, RR (1977) Clinical and biochemical studies on cataractous human lens III. Quantitative study of protein, RNA and DNA. Arogya J Health Sci 3, 69–72.Google Scholar
Reed, LJ & Mukherjee, BB (1969) α-Ketoglutarate dehydrogenase complex from Escherichia coli. Methods Enzymol 13, 55–61.Google Scholar
Sarter, B (2000) Coenzyme Q 10 and cardiovascular disease: a review. J Cardiovasc Nurs 16, 9–20.CrossRefGoogle Scholar
Schneider, WC (1957) Determination of nucleic acids in tissues by pentose analysis. Meth Enzymol 3, 680–684.Google Scholar
Schwartz, MK (1992) Enzymes as prognostic markers and therapeutic indicators in patients with cancer. Clin Chim Acta 206, 77–82.Google Scholar
Senior, AE, McGowan, SE & Hilf, R (1975) A comparative study of inner membrane enzymes and transport systems in mitochondria from R3230AC mammary tumor and normal rat mammary gland. Cancer Res 35, 2061–2067.Google Scholar
Shang, Zhang J, Xu, Y, Sattler, LG & Pilot, CH (1991) DNA damage and repair in γ-glutamyl transpeptidase-positive and negative hepatocytes in primary culture from carcinogen treated rats. Proc Soc Exp Biol Med 196, 47–53.Google Scholar
Shibata, K, Kawada, T & Iwai, K (1987) High performance liquid chromatographic determination of nicotinamide in rat tissue samples and blood after extraction with diethylether. J Chromatogr 422, 257–262.CrossRefGoogle Scholar
Shike, M & Brennan, MF (1993) Supportive care of the cancer patient: nutritional support. In Cancer: Principles and Practice of Oncology, pp. 2029–2044 [DeVita, VT, Hellman, S and Rosenberg, SA, editors]. Philadelphia: JB Lippincott.Google Scholar
Singh, KK (2000) Mitochondrion: me and the mitochondrial journal. Mitochondrion 1, 1–2.Google Scholar
Slater, EC & Bonner, WD (1952) Effect fluoride on succinate oxidase system. Biochem J 52, 185–196.Google Scholar
Sujatha, V, Muthumanickam, V, Rani, G & Sachdanandam, P (1999) Effect of Semecarpus anacardium Linn. nut extract on glucose metabolizing enzymes in experimentally induced mammary carcinoma in rats. J Pharm Pharmacol 51, 241.Google Scholar
Tayek, JA (1992) A review of cancer cachexia and abnormal glucose metabolism in humans with cancer. J Am Coll Nutr 11, 45–56.CrossRefGoogle ScholarPubMed
Tchen, TT & van Milligan, H (1960) The stereospecificity of the succinate dehydrogenase reaction. J Am Chem Soc 82, 4115–4116.CrossRefGoogle Scholar
Tisdale, MJ (1997) Biology of cachexia. J Natl Cancer Inst 89, 1763–1773.CrossRefGoogle ScholarPubMed
Tzagoloff, A (1982) Oxidative pathways in mitochondria. In Mitochondria, pp. 39–60 [Siekevitz, P, editor]. New York: Plenum Press.Google Scholar
Wahrendorf, J, Munoz, N & Lu, JB (1988) Blood, retinol and zinc riboflavin status in relation to precancerous lesions of the esophagus: findings from a vitamin intervention trial in the People's Republic of China. Cancer Res 48, 2280–2283.Google Scholar
Waterhouse, C (1974) Lactate metabolism in patients with cancer cachexia. Cancer 33, 66–71.Google Scholar
Wharton, DC & Tzagoloff, A (1967) Cytochrome oxidase from beef heart mitochondria. Methods Enzymol 10, 245–250.Google Scholar
Williamson, J & Copper, R (1980) Regulation of the citric acid cycle in mammalian systems. FEBS Lett 117, 73–85.Google Scholar