A holistic approach to targeting breast cancer part II: Micronutrient synergy. Presented by: Dr. Neha Shanker DRRI

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1 A holistic approach to targeting breast cancer part II: Micronutrient synergy Presented by: Dr. Neha Shanker DRRI

2 Overview of the previous webinar In the last presentation we talked about: Increase in breast cancer in industrialized nations. Causes: Lifestyle changes, environmental carcinogens, genetics, etc. Normal breast physiology and cyclical changes. Cellular perspective and role of other cells in inhibiting or promoting breast cancer. Chemotherapy, toxicity and severe side effects. Need for holistic approaches.

3 What do we mean by a holistic approach? An approach that: 1. Targets several mechanisms simultaneously. 2. Works in synergy to target disease. 3. Is not toxic. 4. Supports and uses the body s natural defense to collectively work against cancer.

4 Hallmarks of cancer: Uncontrolled cell multiplication Growth of tumor. NO cell death in cancer cells. Unlimited supply of nutrients to cancer cells. Spread to other organs and tissues: Invasion and metastasis Kills!!.

5 Hallmarks of cancer Collagenases: MMPs Collagen fibres Mutated cell

6 Hallmarks of cancer 1. Uncontrolled cell proliferation and tumor growth

7 Hallmarks of cancer 1. Uncontrolled cell proliferation and tumor growth

8 Hallmarks of cancer 1. Uncontrolled cell proliferation and tumor growth Tumor mass Tumor mass

9 2. Angiogenesis: Formation of new blood vessels

10 Hallmarks of cancer 3. Invasion and metastasis

11 Hallmarks of cancer 3. Invasion and metastasis

12 To summarize: A holistic approach should- Holistic approach

13 90% of cancer related deaths occur secondary to metastasis Lymph nodes Capillaries

14 Degradation of surrounding matrix Mutated cell Normal epithelial cell Intact basement membrane Uncontrolled cell proliferation Digested collagen fibers Damaged basement membrane Collagen digesting enzymes

15 Our GOAL Specific nutrients that stabilize tissue collagen and connective tissue: Limit cancer growth Inhibit formation of blood vessels Inhibit metastasis to other organs

16 Our GOAL: Hunt for nutrients! Vitamin C; EGCG Decreased cell proliferation Stable and strenghened collagen fibers Vitamin C; L-Lysine; L-Proline; N-Acetyl glucosamine Reformed basement membrane Decreased Collagen digesting enzymes L-Lysine; L-Proline; EGCG (Green tea extract) No invasion, no metastasis Tumor cells captured in collagen mesh

17 Holistic approach: EGCG (Green tea extract) Inhibitor of specific receptors eg. HER2 (targeted by herceptin), EGFR Curcumin Quercetin Telomerase inhibition Resveratrol Inhibition of MMP enzymes that promote invasion Inhibit angiogenesis Vitamin C Inhibit oxidative stress and DNA damage Promote tumor necrosis and death Cell cycle arrest/ Inhibition of cell growth Lysine, Proline Synthesis and deposition of collagen: Prevention of invasion

18 Nutrient synergy: Mechanistic overlap EGCG (Green tea extract) Curcumin Quercetin Vitamin C Resveratrol Non-Random Specific Micronutrient Mixture Synergistic and amplified effect Effective at lower doses

19 Testing the micronutrients against breast cancer

20 Step I: Effect of treatment on cancer cells Breast cancer cells No treatment Treatment with nutrient mixtures Cell proliferation Cell Death Cell invasion Secretion of collagen digesting enzymes

21 Effect of nutrient mixture on breast cancer cells B Effect of nutrient mixture (NM) on breast cancer cell proliferation Effect of NM on inhibition of invasion of breast cancer cells Roomi et al, Medical Oncology, 2005

22 Step II: Experiments in mice Induction of cancer No treatment Nutrient mixture diet No treatment Nutrient mixture diet

23 Tumor Growth (in vivo) Breast tumor induced in female rat by MNU - Nutrient Synergy decreased weight and number of tumors (MNU)

24 Therapeutic/ Curative aspect of Nutrient Synergy in breast cancer Start of carcinogen* MNU induced Breast cancer progression without intervention Control diet 18 weeks Micronutrient supplemented diets: - Green Tea - NM 8 weeks Study of micronutrient effects on tumor growth FINAL *N- nitroso urea

25 Size of tumors Size of tumors Micronutrient synergy slows down growth of existing tumors Control 2. Addition of micronutrients + Green tea extract only Nutrient Mixture 0 day 20th day 41st day 60th day Intake of micronutrients days 20 Intake of micronutrients (days)

26 Comparative effects of Nutrient Intervention in mnu-induced mammary Tumors Control Number of tumors per rat 4.0 +/-0.9 Green Tea 2.0 +/-1.1 Size of tumors per rat (cc) / /-6 Number of carcinomas (C) and benign (B) tumors C B NM PLUS Quercetin 1.0 +/- 0.5 * 2.7+/-1.7 * 6 15 A. Kale et al, Oncology Letters 2010, 1, * p<0.05

27 Number of tumors counted Nutrient synergy can drastically reduce malignancy of tumors Tumor Type 1 24 Grade I, II and III Benign 15 Control Diet Aggressive 6 Grade I & II Nutrient Synergy A. Kale et al, Oncology Letters 2010, 1,

28 Invasion of More Than 40 Types of Cancer Cells Stopped by Micronutrients Complete Blocking at LOW Micronutrient Concentration Breast cancer Hodgkin-Lymphoma Complete Blocking at MEDIUM Micronutrient Concentration Liver cancer Bladder cancer Kidney cancer Ovarian cancer Prostate cancer Brain cancer (Glioblastoma) Blood cancer (i.e. Leukemia) Complete Blocking at HIGH Micronutrient Concentration Lung cancer Colon cancer Pancreatic cancer Skin cancer (Melanoma) Bone cancer (Osteosarkoma) Testicular cancer Blood cancer (Non-Hodgkin- Lymphoma) Dr. Rat Research Institute

29 Recent studies at DRRI: Q. Where do our products, the micronutrient mixtures stand? In inhibiting cancer cell growth and invasion? In preventing normal cells from becoming allies in promoting metastasis? Normal cells: Major players in MMP secretion and tissue matrix degradation. The role of micronutrients: Reduce MMP expression Prevent ECM degradation Help normal cells to inhibit or limit cancer cell survival.

30 Holistic approach part II: The Tumor Microenvironment: Love thy neighbour! Lu et al, JCB, 2012, 196 (4): 395

31 Effect of Nutrient mixture on modified normal cells MMP enzyme activity by normal cells

32 MMP2 activity MMP2 activity Nutrient mixtures modulate MMP2 activity in HDF cells Control NM1 100 NM1 300 NM1 600 PMA Control NM2 100 NM2 300 NM2 600 PMA HDF treated directly with different concentrations of Nutrient mixture 1 HDF treated directly with different concentrations of nutrient mixture 2

33 MMP2 activity Direct effect of micronutrient mixtures on stimulation of normal cells by cancer cells Normal Cancer cells NM1 Low Conc NM1 High Conc Normal Cancer cells NM2 Low Conc NM2 High Conc

34 Conclusions: It is important to target several mechanisms of cancer in its treatment. Treatments targeting invasion and metastasis improve life expectancy by preventing cancer spread to other organs. Connective tissue structure and collagen synthesis and deposition are of paramount significance. Nutrients supporting and promoting collagen synthesis and connective tissue stability - Ideal candidates for breast cancer treatment. Non-random and measured selection of specific nutrients act synergistically to inhibit breast cancer. Cell culture and mice studies show the supremacy of using a mixture of nutrients rather than single nutrients in treatment of breast cancer. Nutrient mixtures not only inhibit cancer cell invasion, they also support normal cells of the surrounding tissue - Multipronged attack.

35 Thank You

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