PROSTATE CANCER

1. Study of Antioxidant Vitamins, prostate specific antigen and role of insulin resistance in prostate cancer M. Prasad Naidu Ph.D. Scholar, Dept of Biochemistry Narayana Medical College,Nellore. NTR UHS.

2. Dr.M.Krishnamma M.D(Biochemistry),D.G.O Professor, Dept of Biochemistry Narayana Medical College,Nellore.

3. INTRODUCTION • Prostate cancer is the most common malignancy among men in developed and developing countries • Incidence of prostate cancer is 5per 1,00,000 in southern and eastern Asia. • Both genetic and environmental factors have been implicated in its etiology. Prostate specific antigen (PSA) & prostatic acid phosphatase (ACP) are produced in the epithelial cells. Both cell types express androgen receptors, & depend on androgen for growth.(1)

4. The prostate protects itself against electrophilic attacks from carcinogens by inducing a battery of enzymes, of which glutathione S-transferase is the most prominent.2 • The mitogenic and growth stimulatory effects of Insulin growth factor may be involved in prostate carcinogenesis.

6. Insulin suppresses the hepatic synthesis of SHBG, and crosssectional studies reported an inverse correlation between insulin and SHBG levels. • Decreased levels of SHBG result in increased levels of the bioactive free fraction of testosterone entering the prostate cells, which in turn may increase the risk of prostate cancer.

7. Insulin resistance is associated with a higher risk of prostate cancer among men and that insulin sensitivity is associated with a reduced risk of prostate cancer among men.3 •  Both genetic and environmental factors have been implicated in the etiology of prostate cancer. Antioxidants like α tocopheroland selenium may also reduce the risk. • Several molecular etiological pathways have been suggested for prostate cancer–androgen transactivation pathways, insulin like growth factor signaling pathways and chemical carcinogenic pathways.4

8. IGF-1 is known to increase the prostate cancer risk by stimulating cellular proliferation of the prostate, and IGFBP-3 is reported to prevent prostate cancer by blunting the proliferative effect of IGF-1 on prostate cells. • 1,25(OH)2 vitamin D reduces prostate cancer cell growth by multiple mechanisms, which include cell cycle arrest, the induction of apoptosis, and regulation of growth factor signaling.

9. A multidimensional model of cancer development

10. A simple model of prostate cancer development: possible interfaces of etiological path ways.

11. Objectives: • To estimate Prostatic specific antigen . • To estimate Antioxidant vitamins. • To evaluate insulin resistance by HOMA- IR.

12. Materials and method: In our study 30 prostate cancer patients aged 60-80years were taken as cases. 30 normal age matched disease free persons were taken as controls in both groups, antioxidant vitamin and Insulin resistance status was studied.

13. To estimate Antioxidant vitamins by high performance liquid chromatography. • To estimate Prostatic specific antigen by immuno enzymatic assay. • To evaluate insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR). • To estimate plasma Glucose by GOD POD. • HOMA IR= Plasma insulin mIU/LXPlasma glucose mg/dl 405

14. Results • Serum vitamin E and vitamin C values for cases was reduced (p<0.05) significantly than controls. • In the present study, the value of HOMA-IR significantly increased (p<0.05) in cases, compared to controls.

15. The results of the present study are consistent with the findings showing an association between increased insulin resistance, lowered antioxidant vitamin status and the pathogenesis of prostate cancer.

16. Free Radical chain reaction

18. Low level of antioxidant vitamin status and PSA pathogenesis of prostate cancer

19. Increased insulin resistance in prostate cancer.

20. CONCLUSION • The development of prostate cancer is a multistep process. • Hyperinsulinemia associated with insulin resistance may play a role in the pathogenesis of prostate cancer through its sympatho excitatory effect, by altering sex hormone metabolism, activating the IGF pathway, through signal transduction mechanisms and via dyslipidemia and inflammation.

21. Whether increased insulin resistance, either through lifestyle changes or genetic susceptibility, increases the risk of prostate cancer warrants further investigation, especially in prospective studies. • Elevated fasting plasma insulin and other components of the metabolic syndrome were associated with greater prostate cancer mortality. • Prostate cancer cells generate high levels a ROS and the generation of ROS increases with aggressiveness of the cells.

22. Recent work has shown that vitamin E suppresses the expression of androgen receptor in prostate cancer cells and helps to establish new therapeutic concepts for the prevention and treatment of prostate cancer. • Vitamin C has role in regeneration of tocopherol from phenoxy free radical derivative. • A decreased prostate cancer risk was observed with increasing intake of vitamin C-rich vegetables.

23. REFERENCE 1. Harrison principles of internal medicine 16th edition : volume number 1; hyperplastic and malignant diseases of the prostate ; chapter 81; pages 543 -553 2.Campbell’s Urology, 7th Edition ,Edited by Walsh, Retik ,Vaughan , Wein: Volume number 2 :Chapter 45: The molecular biology and endocrinology of the prostate and seminal vesicles. Pages 1381- 1428. 3.Hsing AW , Devesa SS. Trends amd pattern of prostate cancer ; what do they suggest ? Epidemiology review 23 : 30 – 35 , 2001 : Hormones , genes , and cancer Henderson , Ponder , Ross : Oxford university press 2003 : Prostate Cancer: Epidemiology & Molecular biology chapter 15 pages 273 -287 .

24. 4. Insulin Resistance and Prostate Cancer Risk :Ann W. Hsing, Yu-Tang Gao,Streamson Chua, Jr., Jie Deng,Frank Z. Stanczyk: Journal of the National Cancer Institute, Vol. 95, No. 1, January 1, 2003

25. Thank you