Synergistic effect of vitamin E and selenium in human prostate cancer cell lines.

Vitamin E and selenium are the two most popular dietary supplements used to prevent prostate cancer. The hypothesis that these antioxidants reduce prostate risk is being tested in the selenium and vitamin E chemoprevention trial (SELECT). We hypothesize that selenium potentiates vitamin E-induced inhibition of prostate cancer cell growth in vitro. Prostate cancer cell populations growing asynchronously were treated with a combination of vitamin E and selenium and processed for flow cytometric analysis. Prostate cancer cells treated with a combination of the antioxidants revealed that selenium potentiates vitamin E-induced inhibition of LNCaP cells in vitro. This was demonstrated by a reduction in the percentage of cells in the S phase. This crucial finding confirms our previous observations that antioxidant molecules act via distinct mechanistic pathways. These independent biological effects can be exploited in order to augment the anticancer properties of individual agents. These data also validate the two factorial design of the SELECT trial, permitting pairwise comparisons between agents in combination and alone.

Antioxidant dietary supplements: Rationale and current status as chemopreventive agents for prostate cancer.

Epidemiologic data suggest that the environment is responsible for most prostate cancers (PCA). One major mechanism by which the environment can influence carcinogenesis is oxidative damage. This refers to the generation of reactive oxygen species (ROS) that then damage important biomolecules, including DNA, protein, and lipids. Experimental observations suggest that oxidative damage is associated with PCA. These include: a) the association of PCA and dietary fat consumption (a major substrate for oxidative stress), b) oxidative biomarker data (suggesting increased oxidative stress among patients with PCA), c) ubiquitous defects in the glutathione-s-transferase pi pathway (a major endogenous antioxidant mechanism), and d) evidence that androgens (an important promoter of PCA growth) work in part via generation of ROS. Perhaps the best indirect evidence for oxidative stress comes from randomized double-blind prevention trials of antioxidants. Vitamin E and selenium have both been shown to reduce prostate cancer incidence. Although PCA prevention was not the primary endpoint of these studies, the statistical likelihood that both would prove beneficial by chance alone is 1 in 400. These data suggest that antioxidants may be beneficial in preventing PCA. Further research including randomized trials is warranted.

Nutritional aspects of prostate cancer: a review.

OBJECTIVES: The primary prevention of prostate cancer through nutritional modification is becoming a focus of attention as important relationships between diet and cancer are becoming evident. Relevant research is reviewed, along with recent data implicating various vitamin supplements and food products in the prevention and treatment of prostate cancer. METHODS: The epidemiology of prostate cancer, and current knowledge of prevention, screening, and progression of neoplasia is discussed. The current understanding of diet and its importance in primary and secondary prevention is explored. Literature searches were performed on MedLine using relevant keywords to find studies relating to prevention and treatment of prostate cancer using dietary methods. Of these, 104 published manuscripts were used. The search was limited from the year 1975 to the present. RESULTS: Incidence rates for prostate cancer vary according to diet and lifestyle. Several double-blind placebo-controlled clinical trials have shown that supplementation with selenium reduces cancer incidence. Inhibitory effects on the growth of in vitro prostate cancer cell lines have been observed with the administration of soy isoflavones, lycopenes from tomatoes, and vitamin D. Other compounds, such as calcium and fatty acids, have been linked to higher incidences of prostate cancer. CONCLUSIONS: Evidence exists that diet may play an important role in the primary prevention of prostate cancer. Further research is necessary to define the role that nutrition plays in the prevention or promotion of prostate cancer.

Cigarette smoking patterns in patients after treatment of bladder cancer.

BACKGROUND: Assessment of smoking status and identification of those most likely to continue smoking are important in the management of patients who have bladder cancer, because continued smoking following diagnosis and treatment increases the likelihood of treatment-related complications, recurrence, second primary malignancies, and morbidity and mortality. METHODS: Patients (n = 224) receiving follow-up care of previously treated bladder cancers completed a brief written survey assessing their post-diagnosis smoking patterns. RESULTS: Despite the risks of continued smoking, 69% of the patients who had been active smokers at the time of diagnosis (n = 84) reported smoking at some point following the diagnosis and 45% reported smoking at the time of assessment. Patients diagnosed at earlier stages were more likely to continue smoking. Patients diagnosed at later stages were 2.80 times more likely to be continuous abstainers than those diagnosed sooner (95% CI, 1.08-7.25). CONCLUSIONS: The findings underscore the need to assess smoking status and provide smoking-cessation advice and counseling within routine comprehensive care of bladder cancer patients.

Prevalence and patterns of the use of complementary therapies among prostate cancer patients: an epidemiological analysis.

PURPOSE: We determine the prevalence and patterns of the use of complementary therapies among patients with and those at high risk for prostate cancer. MATERIALS AND METHODS: A cross-sectional survey was performed of men presenting to 2 urban tertiary urology clinics for prostate cancer evaluation or followup, and those attending a prostate cancer support group. All men diagnosed with and those at high risk (positive family history or abnormal prostate specific antigen) for prostate cancer were eligible for study. A 9-item self-administered, anonymous questionnaire about complementary therapies was administered. RESULTS: Of 357 patients who received the survey 155 from the urology clinics and 113 from the support group responded, for a total response rate of 75%. Of the patients presenting to urology clinics and the support group 27.4 and 38.9% with and 25.8 and 80% at high risk for prostate cancer, respectively, used some form of complementary therapy. The use significantly differed according to disease status (p = 0.001), and was highest among men who were clinically disease-free after radical therapy. Of the patients 24% did not inform the urologist of using alternative therapy. CONCLUSIONS: The prevalence of the use of complementary therapy among patients with or at increased risk for prostate cancer was high and dependent on the disease state. Urologists should be aware of this pattern of use, and consider the potential effects when assessing patients for and with prostate cancer.

Vitamin E inhibits the high-fat diet promoted growth of established human prostate LNCaP tumors in nude mice.

PURPOSE: Prostate cancer has become an important public health problem in the Western world. It is currently the most common diagnosed cancer and the second leading cause of cancer deaths among North American men. Prostate cancer possesses a unique descriptive epidemiology which suggests that environmental factors (such as dietary fat consumption) play a pivotal role in tumor progression. Data from our institution have demonstrated that diets high in fat content can accelerate the growth of human LNCaP prostate cancer cells. One of the hypothesized mechanisms of dietary fat induced growth is oxidative stress. Our purpose was to determine the effect of supplemental Vitamin E, a potent intracellular antioxidant, on the high-fat promoted growth of transplanted LNCaP cells in the athymic mouse. MATERIALS AND METHODS: Tumors were induced by subcutaneous injection of 10(6) LNCaP cells. Mice were fed a control diet consisting of 40.5% of total calories from dietary fat. Once tumors were formed, PSA values were obtained and animals were randomized into 4 groups of 12. The animals were then assigned to one of 4 dietary plans. Group 1 received the control diet of 40.5%-kcal fat. Group 2 received the 40.5%-kcal fat diet plus supplemental Vitamin E. Group 3 received a diet of 21.2%-kcal fat. Group 4 received the 21.2%-kcal fat diet plus supplemental Vitamin E. Food intake, animal weights, and tumor volumes were recorded weekly. Survival analyses with time to a target volume of 0.523 cm.3 (defined as failure) were used to compare tumor growth among the 4 groups. Two-sided tests (log rank test) with alpha set at 0.05 were used to determine significance. RESULTS: Tumor growth rates were highest in the animals fed a 40.5%-kcal fat diet (p <0.05 group 1). Tumors in animals fed 40.5%-kcal fat plus Vitamin E, 21.2%-kcal fat, and 21.2%-kcal fat plus Vitamin E, experienced statistically indistinguishable growth rates. No significant differences were noted in total ingested calories, animal weight gain or initial PSA levels. CONCLUSIONS: These data suggest that the mechanism of dietary fat induced growth of human prostate cancer cells is mediated by oxidative stress. It also raises the possibility of a therapeutic benefit of vitamin E in preventing prostate cancer.

Diet, androgens, oxidative stress and prostate cancer susceptibility.

Prostate cancer is the most common human malignancy and the second leading cause of cancer deaths among men in Western nations. Descriptive epidemiologic data suggest that androgens and/or environmental exposures, such as diet (in particular, dietary fat), play an important role in prostatic carcinogenesis. One plausible link between diet and prostate cancer is oxidative stress. This process refers to the generation of reactive oxygen species, which can then trigger a host of pro-carcinogenic processes. Recent studies also indicate that androgens increase oxidative stress within human prostate cancer cell lines. Recent data from our institution indicate that oxidative stress is higher within the benign epithelium of prostate cancer patients than men without the disease. This confirms our hypothesis and suggests that antioxidants such as lycopene, vitamin E, and selenium may play an important role in preventing disease progression. Large-scale clinical trials with some of these agents are currently in the design phase.

Cancer of the prostate: a nutritional disease?

UNLABELLED: In summary, epidemiologic and laboratory evidence increasingly demonstrate that nutritional factors, especially reduced fat intake, soy proteins, vitamin E derivatives, and selenium, may have a protective effect against prostate cancer. The experimental observation that low-fat diets and soy protein extracts may influence the progression of established tumors, rather than inhibiting etiologic factors, is particularly intriguing because it may serve to help explain the paradox whereby the incidence of clinical prostate cancer shows wide geographic variation, yet the evidence persists that the incidence of microfocal tumors is essentially the same worldwide. These observations, plus the likelihood that nutrition trials are likely to have little in the way of toxicity that would preclude their completion, argue that such trials should be performed. It is estimated that 30% to 50% of human malignancies may be related to dietary factors, and although the feasibility of trials involving low-fat diets has been proved in ongoing trials for colon and breast cancer, no similar study exists for prostate malignancy. Critics of epidemiologic research argue that data derived from case-control studies are subject to recall bias and are thus artifactual. Indeed, many researchers now believe that the breast cancer-dietary fat hypothesis has been discredited. The major difference between the prostate cancer and breast cancer literature is the remarkable consistency of the cohort studies. In these studies, exposure is determined prospectively and is therefore free from recall bias. In this sense they more closely resemble a clinical trial. The majority of cohort studies involving dietary fat and breast cancer have been negative. We believe that these data justify large-scale trials in the area of prevention of prostate cancer. One such proposed study already submitted for National Institutes of Health funding from a consortium of centers is the Prostate Interventional Nutrition Study (PINS), modeled after the Women's Interventional Nutrition Study, which investigates the effect of low-fat diets in women receiving therapy for node-positive breast cancer. The PINS study will be limited to men who have detectable serum PSA levels but no other clinical evidence of disease after radical prostatectomy. All subjects will receive nutritional guidance, with randomization between a control arm receiving the currently recommended 30% fat diet and an interventional arm in which a 15% fat diet is supplemented with soy protein, vitamin E, and selenium. The end points for evaluation will be compared with progression based on changes in PSA and the time of onset of clinical, as opposed to biochemical, disease. Single-institution trials involving groups thought to be at high risk of developing clinical cancer--including men with persistently elevated PSA levels, two negative prostate biopsies, high-grade prostatic intraepithelial neoplasia on biopsy, and a strong family history of prostate cancer--are being initiated at MSKCC and other institutions. CONCLUSIONS: We have reviewed the evidence that nutritional factors play a role in the progression rate of prostate cancer and may help to explain the geographic variation in the incidence observed. However, without well-controlled prospective trials, the attractive hypothesis that nutrition plays a role in tumor progression remains simply an attractive hypothesis. To date, no definite proof of a preventive effect has been shown in a study that will withstand rigid scientific scrutiny. The opportunity exists, however, for the urologic community, working together with experts in the area of nutrition, not only to advance our understanding of prostate tumorigenesis, but to rebut those critics of modern medical technology who claim that we have ignored the total or holistic approach to healing. (ABSTRACT TRUNCATED)