Stress Proteins & Cancer

1. Stress Proteins & Cancer Presented by: Carolyn Jackson Advisor: Dr E.L. Myles

2. ALL CELLS

3. ALL ORGANISMS

4. Living in the World

5. Must cope with…

6. Stress!!!

7. Introduction • Stresses are defined as forces that on their own, or in combination produce, or sustain a strain. • In biology, stress is the driving force behind the process of adaptation and evolution. • A unique class of proteins; heat shock proteins have evolved to cope with the potential for proteins to become unstable or denatured when stressed and thus act as a defense against protein damage.

8. What are heat shock proteins and how do they work? • Heat shock proteins (HSPs), also called stress proteins, are a group of proteins that are present in all cells in all life forms. • Heat shock proteins stabilize proteins and are involved in the folding of denatured proteins. • HSPs were originally identified in response to heat

9. History Of Heat Shock Proteins • In the early 1960s, F. Ritossa first discovered the heat shock (HS) response while observing the salivary cells of Drosophila melanogaster (Ritossa, 1962). • It was noted that heating these cells induced puffs to form at various regions of the polytene chromosomes. Further analysis revealed that these puffs were actually areas of localized transcription that correlated to the increase of several families of proteins. • this response was termed "heat shock response”  because  heat shock was the most  common  inducer used

10. Heat shock proteins are now known to be induced when a cell undergoes various other types of environmental stresses like cold and oxygen deprivation.

11. Heat shock proteins assist in the recovery from stress either by repairing damaged proteins (protein refolding) or by degrading them, thus restoring protein homeostasis and promoting cell survival.

12. Many  of  these "stress  proteins" are common  to  a variety of stresses  while others are uniquely  induced by a specific stress. • Some are localized to specific organelles and many family members have counterparts, referred to as heat shock cognates (HSCs) that are expressed under normal, non-stress conditions.

13. Other Functions of Stress Proteins • They also shuttle proteins from one compartment to another inside the cell, and transport old proteins to ‘garbage disposals’ inside the cell. • HSPs are also believed to play a role in the presentation of pieces of proteins (or peptides) on the cell surface to help the immune system recognize diseased cells.

14. A variety of chemical agents also induce synthesis of  some of the heat shock proteins in organisms • these include:  oxidizing agents  and  drugs  affecting   energy   metabolism,  transition  series  metals,  sulfhydryl   reagents,  chelating  drugs,  amino   acid  analogues,  certain  inhibitors  of  transcription  and translation,  steroid  hormones, glucose deprivation   ( including treatment with 2-D-glucose, glucosamine, tunicamycin etc.),  ionophores, teratogens, ethanol  etc.

15. Classification • The different major heat shock proteins are  grouped, on the basis  of  their apparent molecular  sizes (in kilodaltons), structure, and function, into different families. • Those families include: Hsp100,  Hsp90,  Hsp70,   Hsp60, HSP40 and the small heat shock proteins family.

17. What do heat shock proteins have to do with preventing cancer?

18. Early Research with HSPs • First research began in the1940’s. • Tumor cells can be weakened, or attenuated, and injected like a vaccine into a mouse. Afterwards, if these same tumor cells, at full strength, are injected into the mouse, the mouse will reject the tumor cells and cancer will not develop. However, if a mouse has not been vaccinated in this manner, the tumor cells will ‘take’ and the mouse will develop cancer.

19. Early studies provided the first hint of the enormous diversity of cancers. • Also showed that the ability of heat shock proteins to prevent cancer was highly specific: For example, cells from tumor X can only vaccinate against tumor X, and vaccination with cells from tumor X does not prevent the development of tumor Y.

20. Tumor used for challenge Tumor used for vaccination + Tumor rejected - Tumor grows

21. What element gave Heat shock proteins their enormous specificity?

22. Dr. Pramod Srivastava • Began a series of experiments about 20 years ago that initially showed the element responsible for protecting the mice was HSPs. • Later showed that heat shock proteins alone could not specifically vaccinate against cancer — but they could when they were bound to short pieces of proteins called peptides. • Went on to become the founder of Antigenics. • Company received the first patent for the vaccine covering the use of HSPs for the treatment of cancer in 1998.

23. Is there a correlation between heat shock proteins and breast cancer?

24. Heat shock proteins (hsps) are thought to play important roles in the cell cycle and cancer progression. • Heat shock proteins (Hsps) are induced in vitro by several cytotoxic drugs; in human breast cancer cells these proteins appear to be involved in anti-cancer drug resistance.

25. Current project proposals • To determine if heat shock proteins are up-regulated in breast cancer cells when exposed to the extracts of certain plants? (E. purpurea, E. pallidae) • To determine the specific hsps whose concentrations will be changed using western blotting techniques.

26. Purple ConeflowerHistory • Echinacea (purpurea, pallidae, angustifolia) • Echinacea has a rich tradition of use by North American Plains Indians who used it medicinally to cure wounds, snakebites, and as a blood purifier.

27. Primary uses of echinacea • Colds, coughs and flu and other upper respiratory conditions • Enlarged lymph glands, sore throat • Urinary tract infections • Other minor infections • May help combat herpes and candida • Wounds, skin regeneration and skin infections (external use) • Psoriasis, eczema and inflammatory skin conditions (external use)

28. Health Benefits of Echinacea • Echinacea increases the "non-specific" activity of the immune system. • In other words, unlike a vaccine which is active only against a specific disease, echinacea stimulates the overall activity of the cells responsible for fighting all kinds of infection. Unlike antibiotics, which are directly lethal to bacteria, echinacea makes our own immune cells more efficient in attacking bacteria, viruses and abnormal cells, including cancer cells.

29. Health Benefits • Echinacea facilitates wound healing, lessens symptoms of and speeds recovery from viruses. • Anti-inflammatory effects make it useful externally against inflammatory skin conditions including psoriasis and eczema. It may also increase resistance to candida, bronchitis, herpes, and other infectious conditions.

31. Why is this research important? • Breast cancer is the most common form of cancer in women in the United States, after skin cancer • Both its cause and its cure remain undiscovered. • one out of nine women will develop breast cancer in her lifetime – a risk that was one out of 14 in 1960. • This year, 39,800 women are expected to die of breast cancer. • Breast cancer is the second leading cause of cancer death for all women (after lung cancer), and the leading overall cause of cancer death in women between the ages of 20 and 59. A woman will die from breast cancer every 13 minutes and over 1 million women in the United States have died of this disease since 1970.

32. Conclusion • If Echinacea's effect on cancer cells can be confirmed by further studies, it could have a significant impact on the medical community's approach to cancer treatment. • May prove useful in helping to design more effective anti-cancer drugs. • May even be useful in developing a possible cure for breast cancer.

33. References • www.antigenics.com. • http://www.biochem.arizona.edu/vierling/research.html • American Cancer Society, Cancer Facts and Figures 2003, January 2003. www.cancer.org. • Biological Research Information Center (BRIC), Pohang 790-784, Korea. • National Alliance of Breast Cancer Organizations

34. Acknowledgements A BIG THANK YOU TO: • Dr. E.L. Myles • Mrs. Yvonne Myles • Dr. Todd Gary • Center of Excellence