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FREE RADICALS
IN
CANCER
SARJAK CHAKRAVARTI
Roll no.:17MPH209
Under guidence of Dr. Snehal Patel
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.
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)
Types of free Radicals
Endogenous
Exogenous
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.
Carbon-
centered
Sulfur
centered
Hydrogen
centered
Oxygen
Types of Exogenous free Radicals
Tobacco
Chromium Gases
Ionising
radiation
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
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.
Some risk factors involves in Cancers
 Age
 Alcohol
 Chronic Inflammation
 Diet
 Hormones
 Infectious Agents
 Obesity
 Radiation
 Sunlight
 Tobacco
General
pathophysiology
of Cancer
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.
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;
Basic fundamental of ROS
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
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.
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.
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.
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.
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,
 Beta-catotene, and
 micronutrients such as antioxidants and anticarcinogens.
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
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
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.
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’2015Free Radicals: Properties, Sources,
Targets, and Their Implication in Various Diseases
Free radicals in Cancer

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Free radicals in Cancer

  • 1. FREE RADICALS IN CANCER SARJAK CHAKRAVARTI Roll no.:17MPH209 Under guidence of Dr. Snehal Patel
  • 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)
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  • 5. Types of free Radicals Endogenous Exogenous
  • 6. 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. Carbon- centered Sulfur centered Hydrogen centered Oxygen
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  • 8. Types of Exogenous free Radicals Tobacco Chromium Gases Ionising radiation
  • 9. 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
  • 10. 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.
  • 11. Some risk factors involves in Cancers  Age  Alcohol  Chronic Inflammation  Diet  Hormones  Infectious Agents  Obesity  Radiation  Sunlight  Tobacco
  • 13. 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.
  • 14. 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;
  • 16. 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
  • 17. 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.
  • 18. 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.
  • 19. 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.
  • 20. 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.
  • 21. 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,  Beta-catotene, and  micronutrients such as antioxidants and anticarcinogens.
  • 22. 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
  • 23. 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
  • 24. 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.
  • 25. 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’2015Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases