FULL COMMUNICATION Dietary Lutein Modulates Growth and Survival Genes in Prostate Cancer Cells Mohamed M. Rafi, 1 Saravanan Kanakasabai, 2 Sarita V. Gokarn, 1 Eric G. Krueger, 2 and John J. Bright 2,3 1 Department of Food Science, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA. 2 Neuroscience Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, Indiana, USA. 3 Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA. ABSTRACT Lutein is a carotenoid pigment present in fruits and vegetables that has anti-inflammatory and antitumor properties. In this study, we examined the effect of lutein on proliferation and survival-associated genes in prostate cancer (PC-3) cells. We found that in vitro culture of PC-3 cells with lutein induced mild decrease in proliferation that improved in combination treatment with peroxisome proliferator-activated receptor gamma (PPARc) agonists and other chemotherapeutic agents. Flow cytometry analyses showed that lutein improved drug-induced cell cycle arrest and apoptosis in prostate cancer. Gene array and quantitative reverse transcription-polymerase chain reaction analyses showed that lutein altered the expression of growth and apoptosis-associated biomarker genes in PC-3 cells. These findings highlight that lutein modulates the ex- pression of growth and survival-associated genes in prostate cancer cells. KEY WORDS:  cancer prevention  carotenoids  lutein  PC-3 cells  prostate cancer INTRODUCTION D ietary nutrients are important regulators of in- flammation and cancer. Lutein is a lipophilic oxycar- otenoid yellow pigment present in green leafy vegetables, fruits such as kiwi and orange, and egg yolk. 1 Lutein and its metabolites can be found in many tissues, including the prostate, colon, and lungs with the highest concentration in the liver. 2 Moreover, lutein and zeaxanthin are the two carot- enoids detected in the macula, retina, and lens region of the eye. 3 Lutein is not synthesized by the human body, but can be consumed mainly through dietary nutrients. Earlier studies have suggested that lutein is capable of preventing cancer and other eye, skin, and heart diseases in human and animals. 4–6 Prostate cancer is a commonly diagnosed cancer and the second leading cause of cancer-related death among men in the United States. 7 The National Cancer Institute estimated about 241,740 new cases and 28,170 deaths due to prostate cancer among American men in 2012. 7 Although there are no definite causes of prostate cancer, the risk factors include tobacco use, car- cinogens, radiation, poor nutritional status and diet, hormones, immune conditions, genetic factors, and age. 8 Current treatment for prostate cancer includes surgery, radiation, hormone and chemotherapy, which yield poor prognosis and toxic side effects. Doxorubicin and Taxol are two chemotherapeutic agents commonly used in treating prostate cancer. 9,10 Temozolomide (TMZ) is an alkylating agent that induces O6-methylguanine formation leading to apoptosis and has been commonly used to treat patients with malignant glioma. 11 However, the influence of lutein on the therapeutic efficacy of TMZ in prostate cancer is not known. Peroxisome proliferator-activated receptor gamma (PPARc) is a nuclear receptor transcription factor that regulates cell growth, differentiation, and homeostasis. 12 PPARc agonists modulate lipid metabolism and glucose homeostasis and have been used as prescription drugs for type 2 diabetes. We and others have shown earlier that PPARc agonists induce growth arrest and apoptosis in different types of tumors. 13–15 Other studies have also demonstrated that PPARc agonists induce growth arrest by modulating the expression and ac- tivation of PPARc in prostate cancer. 15–17 However, the influence of lutein on the inhibition of prostate cancer by these therapeutic agents is not known. In this study, we examined the antitumor effect of lutein in combination with chemotherapeutic agents and PPARc agonists in prostate cancer. We found that lutein induces antitumor effect by modulating growth and survival-asso- ciated genes in PC-3 cells, suggesting its significance in the treatment of prostate cancer. Manuscript received 9 January 2014. Revision accepted 18 June 2014 Address correspondence to: John J. Bright, PhD, Neuroscience Research Laboratory, Methodist Research Institute, Indiana University Health, 1800 N Capitol Avenue, Noyes E-504C, Indianapolis, IN 46202, USA, E-mail: jbright1@iuhealth.org JOURNAL OF MEDICINAL FOOD J Med Food 00 (0) 2014, 1–9 # Mary Ann Liebert, Inc., and Korean Society of Food Science and Nutrition DOI: 10.1089/jmf.2014.0003 1