Free radicals in Cancer

Role of free radicals in Cancer

1. FREE RADICALS IN CANCER SARJAK CHAKRAVARTI Roll no.:17MPH209 Under guidence of Dr. Snehal P atel

2. What are free Radicals ? Free radicals ionised particals in human body. Free radicals are produced by normal cell metabolism or external factor such as polution , cigarette smocking, and radiations etc.. They plays a major role in development of chronic and degenerative disease such as Cancer and Neurodegenerative diseases.

3. How free radicals are formed ? Normally , Bonds don’t split in a way that leaves a molecule with an odd,unpaired electron, But when weak bonds split, free radicals are formed. Free radicals are very unstable and react quickly with other compounds Any free radical involving oxygen can be referred to as Reactive Oxygen Species(ROS)

4. Types of free Radicals

5. Types of Endogenous free Radicals The most important free radicals in the body are the radical derivatives of oxygen better known as reactive oxygen species.

6. Types of Exogenous free Radicals Ionising radiation

7. Cancer and it’s Types Cancer is a group of diseases involving abnormal cell growth,and further it spreads to other parts of the body. Or Cancer develops when normal cells in a particular part of the body begin to grow out of control.  Blood cancer Lung cancer Breast cancer Prostate cancer Uterine cancer ….. And many more

8. Background of Cancer Cancer is the second leading cause of death in the world after cardiovascular diseases .  The word cancer came from a Greek words karkinos to describe carcinoma tumors by a physician Hippocrates (460–370 B.C), but he was not the first to discover this disease. Some of the earliest evidence of human bone cancer was found in mummies in ancient Egypt and in ancient manuscripts dates about 1600 B.C .

9. Some risk factors involves in Cancers Age Alcohol Chronic Inflammation Diet Hormones Infectious Agents Obesity Radiation Sunlight Tobacco

10. General pathophysiology of Cancer

11. Impact of free radicals in cell proliferation -Inflammation begins with a reaction to an irritant or infection that is characterized by movement of fluid and white blood cells into extravascular tissue.

12. Conti… This can activate a process called lipid peroxidation and the arachidonic -acid cascade, with the production of cell-proliferation-stimulating eicosanoids . malondialdehyde (MDA) 4-hydroxynonenol (4-HNE) , The free radicals can also damage DNA and modify the structure and function of cancer-related proteins directly. OH•, hydroxyl radical; O2 –•, superoxide; NO•, nitric oxide;

13. Basic fundamental of ROS

14. Role of ROS in development of Cancer It is well known that species derived from oxygen are cytotoxic and are involved in the etiology of cancer . Several carcinogens during metabolism exert their effect by producing reactive oxygen species ( ROS), It plays a vital role in the process of carcinogenesis ROS are generated specifically to answer necessary biological functions, whereas in other cases, they indicate byproducts of metabolic processes. Free radical linked damage of Proteins and DNA has been suggested to play a major role in the development of diseases such as neurodegenerative disorders, arthritis, arteriosclerosis, cancer , and others diseases

15. Role of ROS in development of Cancer Some researches says reducing and inactivation of antioxidant system, the oxidative stress (OS) in cancer cells is higher , Cancer cells exhibit a higher oxidative stress level compared to normal cells. Alterations , including rearrangement of DNA sequence , base modification , DNA miscoding lesions , gene amplification , and activation of oncogenes , could be implicated in the initiation stage of several cancers.

16. Couses of oxydative stress involving in Carcinogenesis Oxidative stress  is an imbalance between the production of free radicals and the ability of the body to detoxify their harmful effects by antioxidants.

17. Free radical damage in DNA and cause Cancer DNA is a major target of free radicals to damage The types of damages includes strand breaks ( single or double strand breaks), various forms of base damage yielding products such as 8-hydroxyguanosine, thymine glycol etc . These damages can result mutations that are heritable change in the DNA that can yield cancer in somatic cells.

18. Conti… Cancer develops through an accumulation of genetic changes. Initiating agents can be Tobacco smoking and chewing, UV rays of sunlight, Radiation, Viruses, Chemical pollutants, etc. Promoting agents include hormones Example: Androgens for prostate cancer, estrogens for breast cancer and ovarian cancer.

19. How to prevent cancer Experimental as well as epidemiological data indicate that a variety of nutritional factors can act as antioxidants and inhibit the process of cancer development and reduce cancer risk. Some of these include vitamins A , vitamin C , vitamin E, B eta- catotene , and micronutrients such as antioxidants and anticarcinogens .

20. Turmeric as a therapeutic agent in Cancer Inflammation induces iNOS ( inducible nitric oxide synthase) as well as COX and LOX. These can initiate carcinogenesis . The active principle of Curcuma longa (Turmeric, Haldi ) - curcumin , down-regulates the expression of COX2, LOX, iNOS , MMP-9, TNF, chemokines and other cell-surface adhesion molecules. Human clinical trials have shown safety at doses upto 10 g/day curcumin, which can suppress tumour initiation, promotion and metastasis

21.  Vitamin C Chelation In a study published in Free Radical Biology & Medicine, vitamin C chelation therapy was found to be highly pro-oxidant after just one hour of treatment. This benefit lasted more than 16 treatments in the absence of nutrient supplementation and even provided “beneficial long-term antioxidant effects .” It was discovered that, “Pro-oxidant effects appear to be responsible for destroying tumor cells. These pro-oxidant effects may also induce endogenous antioxidant systems in normal tissues that offer protection against carcinogenic insult

22. Curcumin as a therapeutic agent in Cancer   Number of laboratory studies on cancer cells suggest that curcumin does have anticancer effects. It seems to be able to fight cancer cells and prevent more from growing. It seems to be most effective against  breast cancer ,  bowel cancer ,  stomach cancer  and  skin cancer  cells . Researchers have reported that curcumin block the formation of cancer-causing enzymes in rodents in preclinical trials.

23. REFERENCES Phaniendra et al. Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases. D. Dreher et al . Role of Oxygen Free Radicals in Cancer Development. Pourahmad and Salimi et al . Role of Oxygen Free Radicals in Cancer Development and Treatment. Ghaskadbi and lele et al.2004 Free Radicals and Antioxidants in Human Health: Current Status and Future Prospects Phaniendra and Jestadi et al’2015 Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases