Inhibition of pancreatic cancer growth by the dietary isoprenoids farnesol and geraniol


Fruits and vegetables have protective effects against many human cancers, including pancreatic cancer. Isoprenoids are one class of phytochemicals which have antitumor activity, but little is known about their effects on cancer of the pancreas. We tested the hypothesis that isoprenoids would inhibit the growth of pancreatic tumor cells. Significant (60–90%) inhibition of the anchorage-independent growth of human MIA PaCa2 pancreatic tumor cells was attained with 25 μM farnesol, 25 μM geranylgeraniol, 100 μM perillyl amine, 100 μM geraniol, or 300 μM perillyl alcohol. We then tested the relative in vivo antitumor activities of dietary farnesol, geraniol, and perilyl alcohol against transplanted PC-1 hamster pancreatic adenocarcinomas. Syrian Golden hamsters fed geraniol or farnesol at 20 g/kg diet exhibited complete inhibition of PC-1 pancreatic tumor growth. Both farnesol and geraniol were more potent than perillyl alcohol, which inhibited tumor growth by 50% at 40 g/kg diet. Neither body weights nor plasma cholesterol levels of animals consuming isoprenoid diets were significantly different from those of pair-fed controls. Thus, farnesol, geraniol, and perillyl alcohol suppress pancreatic tumor growth without significantly affecting blood cholesterol levels. These dietary isoprenoids warrant further investigation for pancreatic cancer prevention and treatment.

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  1. 1.

    Steinmetz, K.A., and Potter, J.D. (1991) Vegetables, Fruit, and Cancer. I. Epidemiology, Cancer Causes and Control 2, 325–357.

    PubMed  CAS  Article  Google Scholar 

  2. 2.

    Block, G., Patterson, B., and Subar, A. (1992) Fruit, Vegetables, and Cancer Prevention: A Review of the Epidemiological Evidence, Nutr. Cancer 18 1–29.

    PubMed  CAS  Article  Google Scholar 

  3. 3.

    Ji, B.T., Chow, W.H., Gridley, G., McLaughlin, J.K., Dai, Q., Wacholder, S., Hatch, M.C., Gao, Y.T., and Fraumeni, J.F. (1995) Dietary Factors and the Risk of Pancreatic Cancer: A Case-Control Study in Shanghai, China, Cancer Epidemiology, Biomarkers & Prevention 4, 885–893.

    CAS  Google Scholar 

  4. 4.

    McGarvey, D.J., and Croteau, R. (1995) Terpenoid Metabolism, Plant Cell 7, 1015–1026.

    PubMed  CAS  Article  Google Scholar 

  5. 5.

    Bansal, V.S., and Vaidya, S. (1994) Characterization of Two Distinct Allyl Pyrophosphatase Activities from Rat Liver Microsomes, Arch. Biochem. Biophys. 315, 393–399.

    PubMed  CAS  Article  Google Scholar 

  6. 6.

    Case, G.L., He, L., Mo, H., and Elson, C.E. (1995) Induction of Geranyl Pyrophosphate Pyrophosphatase Activity by Cholesterol-Suppressive Isoprenoids, Lipids 30, 357–359.

    PubMed  CAS  Google Scholar 

  7. 7.

    Goldstein, J.L., and Brown, M.S. (1990) Regulation of the Mevalonate Pathway, Nature 343, 425–430.

    PubMed  CAS  Article  Google Scholar 

  8. 8.

    Elson, C.E., and Yu, S.G. (1994) The Chemoprevention of Cancer by Mevalonate-Derived Constituents of Fruits and Vegetables, J. Nutr. 124, 607–614.

    PubMed  CAS  Google Scholar 

  9. 9.

    Elegbede, J.A., Elson, C.E., Qureshi, A., Tanner, M.A., and Gould, M.N. (1984) Inhibition of DMBA-Induced Mammary Cancer by the Monoterpene d-Limonene, Carcinogenesis 5, 661–665.

    PubMed  CAS  Google Scholar 

  10. 10.

    Elson, C.E., Maltzman, T.H., Boston, J.L., Tanner, M.A., and Gould, M.N. (1988) Anticarcinogenic Activity of d-Limonene During the Initiation and Promotion-Progression Stages of DMBA-Induced Rat Mammary Carcinogenesis, Carcinogenesis 9, 331–332.

    PubMed  CAS  Google Scholar 

  11. 11.

    Maltzman, T.H., Hurt, L.M., Elson, C.E., Tanner, M.A., and Gould, M.N. (1989) The Prevention of Nitrosomethylurea-Induced Mammary Tumors by d-Limonene and Orange Oil, Carcinogenesis 10, 781–785.

    PubMed  CAS  Google Scholar 

  12. 12.

    Wattenberg, L.W., and Coccia, J.B. (1991) Inhibition of 4-(methylnitrosoamino)-1-butanone Carcinogenesis in Mice by d-Limonene and Orange Oil, Carcinogenesis 12, 115–117.

    PubMed  CAS  Google Scholar 

  13. 13.

    Haag, J.D., Lindstrom, M.J., and Gould, M.N. (1992) Limonene-Induced Regression of Mammary Carcinomas, Cancer Res. 52, 4021–4026.

    PubMed  CAS  Google Scholar 

  14. 14.

    Crowell, P.L., and Gould, M.N. (1994) Chemoprevention and Therapy of Cancer by d-Limonene, CRC Crit. Rev. Oncogenesis 5, 1–22.

    CAS  Google Scholar 

  15. 15.

    Mills, J.J., Chari, R.S., Boyer, I.J., Gould, M.N., and Jirtle, R.L. (1995) Induction of Apoptosis in Liver Tumors by the Monoterpene Perillyl Alcohol, Cancer Res. 55, 979–983.

    PubMed  CAS  Google Scholar 

  16. 16.

    Haag, J.D., and Gould, M.N. (1994) Mammary Carcinoma Regression Induced by Perillyl Alcohol, A Hydroxylated Analog of Limonene, Cancer Chemother. Pharmacol. 34, 477–483.

    PubMed  CAS  Google Scholar 

  17. 17.

    Stark, M.J., Burke, Y.D., McKinzie, J.H., Ayoubi, A.S., and Crowell, P.L. (1995) Chemotherapy of Pancreatic Cancer with the Monoterpene Perillyl Alcohol, Cancer Lett. 96, 15–21.

    PubMed  CAS  Article  Google Scholar 

  18. 18.

    Shoff, S.M., Grummer, M., Yatvin, M.B., and Elson, C.E. (1991) Concentration-Dependent Increase of Murine P388 and B16 Population Doubling Time by the Acyclic Monoterpene Geraniol, Cancer Res. 51, 37–42.

    PubMed  CAS  Google Scholar 

  19. 19.

    Yu, S.G., Hildebrandt, L.A., and Elson, C.E. (1995) Geraniol, An Inhibitor of Mevalonate Biosynthesis, Suppresses the Growth of Hepatomas and Melanomas Transplanted to Rats and Mice, J. Nutr. 125, 2763–2767.

    PubMed  CAS  Google Scholar 

  20. 20.

    Adany, I., Yazlovitskaya, E.M., Haug, J.S., Voziyan, P.A., and Melnykovych, G. (1994) Differences in Sensitivity to Farnesol Toxicity Between Neoplastically- and Nonneoplastically-Derived Cells in Culture, Cancer Lett. 79, 175–179.

    PubMed  CAS  Article  Google Scholar 

  21. 21.

    Haug, J.S., Goldner, C.M., Yazlovitskaya, E.M., Voziyan, P.A., and Melnykovych, G. (1994) Directed Cell Killing (Apoptosis) in Human Lymphoblastoid Cells Incubated in the Presence of Farnesol: Effect of Phosphatidylcholine, Biochim. Biophys. Acta 1223, 133–140.

    PubMed  CAS  Article  Google Scholar 

  22. 22.

    Voziyan, P.A., Haug, J.S., and Melnykovych, G. (1995) Mechanism of Farnesol Cytotoxicity: Further Evidence for the Role of PKC-Dependent Signal Transduction in Farnesol-Induced Apoptotic Cell Death, Biochem. Biophys. Res. Comm. 212, 479–486.

    PubMed  CAS  Article  Google Scholar 

  23. 23.

    American Cancer Society (1996) Cancer Facts and Figures-1996, American Cancer Society, New York, New York, USA.

    Google Scholar 

  24. 24.

    Egami, H., Takiyama, Y., Cano, M., Houser, W.H., and Pour, P.M. (1989) Establishment of Hamster Pancreatic Ductal Carcinoma Cell Line (PC-1) Producing Blood Group-Related Antigens, Carcinogenesis 10, 861–869.

    PubMed  CAS  Google Scholar 

  25. 25.

    Egami, H., Tomioka, T., Terpero, M., Kay, D., and Pour, D.M. (1991) Development of an Intrapancreatic Transplantable Model of Pancreatic Duct Adenocarcinoma in Syrian Golden Hamsters, Am. J. Pathol. 138, 557–561.

    PubMed  CAS  Google Scholar 

  26. 26.

    Phillips, L.R., Malspeis, L., and Supko, J.G. (1995) Pharmacokinetics of Active Drug Metabolites After Oral Administration of Perillyl Alcohol, An Investigational Antineoplastic Agent, to the Dog, Drug Metab. Dispos, 23, 676–680.

    PubMed  CAS  Google Scholar 

  27. 27.

    Fliesler, S.J., and Keller, R.K. (1995) Metabolism of [3H]-Farnesol to Cholesterol and Cholesterogenic Intermediates in the Living Rat Eye, Biochem. Biophys. Res. Comm. 210, 695–702.

    PubMed  CAS  Article  Google Scholar 

  28. 28.

    Chadha, A., and Madyastha, K.M. (1984) Metabolism of Geraniol and Linalool in the Rat and Effects on Liver and Lung Microsomal Enzymes, Xenobiotica 14, 365–374.

    PubMed  CAS  Article  Google Scholar 

  29. 29.

    Clegg, R.J., Middleton, B., Bell, D., and White, D.A. (1980) Inhibition of Hepatic Cholesterol Synthesis and (S)-3-Hydroxy-3-Methylglutaryl-CoA Reductase by Mono and Bicyclic Monoterpenes Administered in vivo, Biochem. Pharmacol. 29, 2125–2127.

    PubMed  CAS  Article  Google Scholar 

  30. 30.

    Clegg, R.J., Middleton, B., Bell, D., and White, D.A. (1982) The Mechanism of Cyclic Monoterpene Inhibition of Hepatic 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase in vivo in the Rat, J. Biol. Chem. 257, 2294–2299.

    PubMed  CAS  Google Scholar 

  31. 31.

    Qureshi, A.A., Mangels, W.R., Din, Z.A., and Elson, C.E. (1988) Inhibition of Hepatic Mevalonate Biosynthesis by the Monoterpene, d-Limonene, J. Agric. Food Chem. 36, 1220–1224.

    CAS  Article  Google Scholar 

  32. 32.

    Ren, Z., and Gould, M.N. (1994) Inhibition of Ubiquinone and Cholesterol Synthesis by the Monoterpene Perillyl Alcohol, Cancer Lett. 76, 185–190.

    PubMed  CAS  Article  Google Scholar 

  33. 33.

    Correll, C.C., Ng, L., and Edwards, P.A. (1994) Identification of Farnesol as the Nonsterol Derivative of Mevalonic Acid Required for the Accelerated Degradation of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase, J. Biol. Chem. 269, 17390–17393.

    PubMed  CAS  Google Scholar 

  34. 34.

    Meigs, T.E., Roseman, D.A., and Simone, R.D. (1996) Regulation of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Degradation by the Nonsterol Mevalonate Metabolite Farnesol in vivo, J. Biol. Chem. 271, 7916–7922.

    PubMed  CAS  Article  Google Scholar 

  35. 35.

    Forman, B.M., Goode, E., Chen, J., Oro, A.E., Bradley, D.J., Perlmann, T., Noonan, D.J., Burka, L.T., McMorris, T., Lamph, W.W., Evans, R.M., and Weinberger, C. (1995), Identification of a Nuclear Receptor That Is Activated by Farnesol Metabolites, Cell 81, 687–693.

    PubMed  CAS  Article  Google Scholar 

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Correspondence to Pamela L. Crowell.

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Burke, Y.D., Stark, M.J., Roach, S.L. et al. Inhibition of pancreatic cancer growth by the dietary isoprenoids farnesol and geraniol. Lipids 32, 151 (1997).

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  • Pancreatic Cancer
  • Isoprenoids
  • Pancreatic Tumor
  • Monoterpene
  • Geraniol