© 2006 American Association for Cancer Research
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Combined Inhibitory Effects of Curcumin and Phenethyl Isothiocyanate on the Growth of Human PC-3 Prostate Xenografts in Immunodeficient Mice
1 Center for Cancer Prevention Research, 2 Department of Pharmaceutics, and 3 Susan Lehman Cullman Laboratory of Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey
Requests for reprints: Ah-Ng Tony Kong, Department of Pharmaceutics, Rutgers, The State University of New Jersey, 160 Freilinghuysen Road, Piscataway, NJ 08854-8020. Phone: 732-445-3831; Fax: 732-445-3134; E-mail: kongt@rci.rutgers.edu .
Earlier studies using prostate cancer cells in culture showed that phenethyl isothiocyanate (PEITC) and curcumin have significant chemopreventive and possibly chemotherapeutic effects. However, their in vivo effects are still lacking. Hence, this study was undertaken to determine the possible in vivo efficacy of prostate cancer-prevention as well as cancer-therapeutic treatment by PEITC and curcumin alone or in combination. We evaluated the effects on tumor growth in vivo, using NCr immunodeficient (nu/nu) mice bearing s.c. xenografts of PC-3 human prostate cancer cells. Molecular biomarkers representing proliferation and apoptosis were determined. Continued i.p. injection of curcumin or PEITC (6 and 5 µmol; thrice a week for 28 days), beginning a day before tumor implantation significantly retarded the growth of PC-3 xenografts. Combination of i.p. administration of PEITC (2.5 µmol) and curcumin (3 µmol) showed stronger growth-inhibitory effects. Next, we evaluated the cancer-therapeutic potential of curcumin and PEITC in mice with well-established tumors, and the results showed that PEITC or curcumin alone had little effect, whereas combination of curcumin and PEITC significantly reduced the growth of PC-3 xenografts. Immunohistochemistry staining and Western blot analysis revealed that the inhibition of Akt and nuclear factor-
B signaling pathways could contribute to the inhibition of cell proliferation and induction of apoptosis. Taken together, our results show that PEITC and curcumin alone or in combination possess significant cancer-preventive activities in the PC-3 prostate tumor xenografts. Furthermore, we found that combination of PEITC and curcumin could be effective in the cancer-therapeutic treatment of prostate cancers. (Cancer Res 2006; 66(2): 613-21)
Curry and Cauliflower Could Halt Prostate Cancer
The discovery was announced in the Jan. 15 issue of the journal Cancer Research by Kong and his colleagues at Rutgers' Ernest Mario School of Pharmacy.
Prostate cancer is the second leading cause of cancer death in men in the United States, with a half-million new cases appearing each year. The incidence and mortality of prostate cancer have not decreased in past decades despite tremendous efforts and resources devoted to treatment. This is because advanced prostate cancer cells are barely responsive even to high concentrations of chemotherapeutic agents or radiotherapy.
The authors noted that in contrast to the high incidence of prostate cancer in the United States, the incidence of this disease is very low in India. This has been attributed to the dietary consumption of large amounts of plant-based foods rich in phytochemicals - nonnutritive plant chemicals that have protective or disease-preventive properties.
Consequently, scientists have been investigating intervention options based on compounds found in edible and medicinal plants. They have had some success, and a majority of patients with prostate cancer are now combining the conventional therapies with these compounds as alternative, supplementary or complementary medications.
For Kong's study, researchers used mice bred so that their immune systems would not reject foreign biological material and injected the mice with cells from human prostate cancer cell lines to grow tumors against which the compounds could be tested.
"Despite convincing data from laboratory cell cultures, we knew little about how PEITC and curcumin would perform in live animals, especially on prostate cancer," Kong said. "So we undertook this study to evaluate how effective PEITC and curcumin might be - individually and in combination - to prevent and possibly treat prostate cancer."
The researchers injected the mice with curcumin or PEITC, alone or in combination, three times a week for four weeks, beginning a day before the introduction of the prostate cancer cells. They found the injections significantly retarded the growth of cancerous tumors. Using PEITC and curcumin in tandem produced even stronger effects.
The group went on to evaluate the therapeutic potential of curcumin and PEITC in mice with well-established tumors, and the results showed that PEITC or curcumin alone had little effect, whereas the combination of curcumin and PEITC significantly reduced tumor growth.
The paper, "Combined Inhibitory Effects of Curcumin and Phenethyl Isothiocyanate on the Growth of Human PC-3 Prostate Xenografts in Immunodeficient Mice," is available at cancerres.aacrjournals.org.
The authors are Tin Oo Khor, Young-Sam Keum, Wen Lin, Jung-Hwan Kim, Rong Hu, Guoxiang Shen, Changjiang Xu, Avanthika Gopalakrishnan, Bandaru Reddy, Xi Zheng, Allan H. Conney and Ah-Ng Tony Kong, all from Rutgers. Source: Rutgers, the State University of New Jersey