1. Galectin-3 and the Role of
Modified Citrus Pectin
and Botanicals in
Integrative Oncology

2. What is Galectin-3?
• Member of soluble β galactoside-binding
lectins
• Plays important regulatory roles in
cancer, inflammation, fibrosis, and
immunologic response
• Expressed in the
nucleus, cytoplasm, mitochondria, cell
surface, and circulation

3. Galectin-3 Plays Regulatory
Role in Inflammation
Biologically active marker for high risk
Unlike CRP which represents the result
or “bystander” biomarker, Galectin-3 is
a “culprit” biomarker
• Promotes metastasis, inflammation &
fibrosis
• Predicts outcome

4. Galectin-3 Levels & Mortality from All Causes
in the General Population: PREVEND1
Median
Galectin-3
Levels
Overall
Average
Number of Subjects n = 7,968 11.9

5. Galectin-3 & Cancer
• In Cancer, Galectin-3 plays a role in:
• Cell to Cell Adhesion
• Aggregation of Cancer Cells
• Tumor Growth
• Metastasis
• Angiogenesis
• Inhibition of Apoptosis

7. Blood Vessel

8. Blood Vessel

12. Modified Citrus Pectin
and Galectin-3

13. What is Modified Citrus Pectin (MCP?)
• MCP is derived from the pith of citrus fruit peels –
oranges, lemons, grapefruit
• Complex polysaccharide fiber of repeating galacturonic acid groups
with neutral sugar side chains
• Unmodified citrus pectin molecular weight 50 to 300 kiloDaltons
(kDa) with esterification ~70%
• Optimal biological activity: molecular weight <13 kDa with
esterification <10%, and specific structure

14. Modified Citrus Pectin is a Galectin-3
Blocker
• Binds to Galectin-3 molecules
• Blocks aggregation of cancer cells
• Blocks docking of cancer cells
• Blocks interactions with endothelium
necessary for angiogenesis

15. Modified Citrus Pectin and
Galectin-3

16. Modified Citrus Pectin
Cancer Research

17. Benefits of MCP in Cancer Treatment
• Anti-Cancer and Anti-Metastasis
• Blocking of Galectin-3 Effects
• Synergistic Effect with Chemotherapy
• Protection Against Post-Radiation Damage
• Improved Quality of Life

18. Inhibition of Spontaneous Metastasis in a Rat
Prostate Model by Oral Administration of
Modified Citrus Pectin2
Pienta KJ, Naik H, Akhtar A, Yamazaki K, Replogle, TS, Lehr J, Donat TL, Tait L, Hogan V, Raz A
Wayne State University School of Medicine, Detroit, MI, USA
J Natl Cancer Inst. 1995 87(5):348-53
• Method: MCP’s inhibition of prostate cell adhesion to
endothelial cells.
0.1% and 1.0% MCP in rats’ drinking water; controls had plain
water.
• Results: Significant reduction in lung metastases -- 50%
reduction in 0.1% group; 56% reduction in 1.0% group (P<0.03
& P<0.001).
• Conclusion: MCP acted as potent inhibitor of spontaneous
prostate carcinoma metastasis.

19. Inhibition of Human Cancer Cell Growth & Metastasis
in Nude Mice by Oral Intake of Modified Citrus Pectin3
Nangia-Makker P, Hogan V, Honjo Y, Baccarini S, Tait L, Bresalier R, Raz A
Wayne State University, School of Medicine, Detroit, MI, USA
J Natl Cancer Inst. 2002 94(24): 1854-62
• Method: MCP’s inhibition of breast & colon cancer progression; MCP’s
interaction with Galectin-3.
• Results: 70.2% Reduction in Breast Tumor Growth
– Breast Angiogenesis: 66% Reduction
– Breast to Lung Metastasis: 0% MCP v. 100% Control
– Colon to Liver Metastasis: 0% MCP v. 60% Control
– Colon to Lymph Metastasis: 25% MCP v. 100% Control
• Conclusion: MCP inhibits carbohydrate mediated tumor
growth, angiogenesis & metastasis via effects on Galectin-3 function.

20. Modified Citrus Pectin Induces Cytotoxicity of Prostate
Cancer Cells in Co-Culture with Human Endothelial
Monolayers4
Weiss T, McCulloch M, Eliaz I
Amitabha Medical Clinic & Healing Center, Sebastopol, CA, USA
EcoNugenics, Santa Rosa, CA,USA
Intl Conference on Diet & The Prevention of Cancer 1999, Tampere, Finland
90% 76.9%
80.7% • Method: Human
80%
vascular endothelial cell
% Cytotoxicity
70%
60% layer & PC-3 prostate
50% cancer cells.
40%
30% • Results: Strong tumor
20%
10%
3.8% cell death response
0% with MCP, compared to
Control 0.1% 1.0%
controls.

21. Effect of Modified Citrus Pectin on PSA Doubling Time
in Prostate Cancer Patients: A Pilot Clinical Trial5
Strum S, Scholz M, McDermed J, McCulloch M, Eliaz, I
Prostate Oncology Specialist, Marina del Rey, CA, USA
Amitabha Medical Clinic & Healing Center, Sebastopol, CA, USA
EcoNugenics, Santa Rosa, CA, USA. International Conference on Diet & The
Prevention of Cancer 1999, Tampere, Finland
• Method: MCP 15 g/day
80% 71%
to patients with
70%
biochemical relapse
% Increase in PSADT
60%
50%
post local therapy. PSA
40%
Doubling Time (PSADT)
30% evaluated at intervals.
14% 14%
20% • Results: MCP
10% significantly increased
0% PSADT in prostate
No Response Stable Disease Response
cancer patients.

22. Pilot Clinical Results: MCP’s Effect on
PSA Doubling Time5
MCP Use PSADT
Patient (Months) Change Status
Patient 1 5 193% Response
Patient 2 6 193% Response
Patient 3 3 80% Response
Patient 4 >15 55% Response
Patient 5 6 6% P. Response
Patient 6 6 -7% Stable Disease
Patient 7 5 -69% No Response

23. Modified Citrus Pectin Increases the Prostate-Specific
Antigen Doubling Time in Men with Prostate Cancer: A
Phase II Pilot Study6
Guess BW, Scholz MC, Strum SB, Lam RY, Johnson HJ, Jennrich RI
Healing Touch Oncology, Marina del Rey, CA, USA
Prostate Cancer & Prostatic Disease 2003;6(4):301-4
• Method: 10 men with biochemical prostate
cancer relapse used MCP: 15g daily for 1 year.
• Results: MCP significantly increased PSADT in 7
out of the 10 participants (p<0.01).

24. PSADT as % of Pre MCP
50%
100%
150%
200%
250%
300%
350%
400%
450%
500%
0%
*
Patient-1
*
Patient-2
Patient-3
Patient-4
Phase II Study:
Post-MCP
Patient-5
Patient-6
Pre-MCP
Patient-7
PSADT Results After 1 Year6
Patient-8
Patient-9
Patient-10
968 %

25. Using Splines to Detect Changes in
PSA Doubling Times7
Guess B, Jennrich R, Johnson H, Redheffer R, Scholz M, Healing Touch Oncology, Marin del
Ray, CA, Department of Statistics, University of California Los Angeles, CA, Department of
Mathematics, University of California - Los Angeles, CA, The Prostate 2003 54:88-95

26. Typical Patient Results7
MCP

27. Clinical Benefit in Patients with
Advanced Solid Tumors Treated with
Modified Citrus Pectin8
Azémar M, Hildenbrand B, Haering B, Heim ME, Unger C
Albert-Ludwigs-University in Freiburg, Germany
Sonnenberg-Klinik, Bad Sooden-Allendorf, Germany
Clinical Medicine: Oncology 2007 1:73–80
• Method: MCP 15g daily.
• Results: 49 patients with advanced solid tumors. 29 evaluated
after 2 months -- 21% showed stabilization & improvements in
quality of life.
– One patient w/ metastasized prostate carcinoma showed 50% decrease in
PSA, with significant increase in quality of life & decrease in pain.
• Conclusion: MCP shows clinical benefits & improvements in
quality of life in advanced cancer patients.

28. Inhibitory Effect of Modified Citrus Pectin
on Liver Metastasis in a Mouse
Colon Cancer Model9
Liu HY, Huang ZL, Yang GH, Lu WQ, Yu NR
Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou, China
World J Gastroenterol 2008 14(48): 7386-7391
• Method: 5 groups of 15 mice.
MCP: 0.0%, 1.0%, 2.5% and 5.0%; and negative
control
– Colon cancer cells injected into spleen except negative control -- liver
metastasis observed after 3 wks. ELISA used to detect Galectin-3.
• Results: MCP groups: metastasis 80%, 73.3% & 60%.
MCP 0.0%: metastasis100%.
• Conclusion: MCP significantly reduced liver
metastasis.

29. PectaSol-C Modified Citrus Pectin Induces Apoptosis &
Inhibition of Proliferation in Human & Mouse Androgen
Dependent & Independent Prostate Cancer Cells10
Yan J, Katz A
Department of Urology, Columbia University Medical Center, New York, NY, USA
Integrative Cancer Therapies 2010 9:197-203
• Method: 1% MCP treatment of human prostate cancer cell
lines (LNCaP & PC3) and mouse prostate cancer cell lines
(CASP2-1 & CASP1-1)
• Results: Confirmed apoptosis and inhibition of cancer cell
proliferation.
4 day MCP treatment showed cytotoxicity:
– 52.28% in LNCaP
– 48.16% in PC3
– 23.03% in CASP2-1
– 49.01% in CASP1-1

30. Combination Effect of PectaSol and Doxorubicin on
Viability, Cell Cycle Arrest and Apoptosis in DU-145 and
LNCaP Prostate Cancer Cell Lines11
Najmeh T, Houri S, Parvin M, Firouzeh B, Arash HN, Abdolfattah S, Ebrahim H
Tehran University, Tehran, Iran
Cell Biology International (2012) Immediate Publication, doi:10.1042/CBI20110309
• Method: 48 hour effects of PectaSol on Doxorubicin (Dox)
cytotoxicity, apoptosis and cell cycle in prostate cancer cell lines.
% Viability DU-145 % Viability LNCaP
100 IC50 Decrease: 1.5 fold 100 IC50 Decrease: 1.3 fold
80 80
60 60
40 40
20 20
0 0
Control 250nM 3mg/ml 250nM + Control 250nM 3mg/ml 250nM + 3
Dox PectaSol 3 mg/ml Dox PectaSol mg/ml
Combined Combined
• Conclusion: Lower, less toxic doses Dox needed when combined with PectaSol.

31. MCP During Chemotherapy &
Radiation
• MCP can enhance therapeutic effect of
chemotherapy drugs and treatment of chemo
resistant cancers. 11, 12
Cisplatin (Platinol), Bortezomib (Velcade), Dexamethasone
(Decadron), Doxorubicin.
• MCP use very important in preventing
post chemotherapy & radiation damage
Specifically post radiation induced inflammation and
fibrosis

32. Summary: MCP in Cancer Treatment
MCP Reduces:
• Primary Tumor
• Angiogenesis
• Metastatic Process
MCP Provides:
• Blocking of Galectin-3 Effects
• Synergistic Effect with Chemotherapy
• Protection Against Post-radiation
Damage
• Improved Quality of Life

33. Modified Citrus Pectin
Immune Research

34. Activation of Human T-Cytotoxic Cell, B-Cell, and
Natural Killer (NK)-Cells and Induction of NK-Cell Activity
Against K562 Chronic Myeloid Leukemia Cells with
Modified Citrus Pectin 13
Ramachandran C, Wilk, B, Hotchkiss, A, Eliaz, I & Melnick SJ; Dharma
Biomedical, Miami, FL, USA; EcoNugenics, Santa Rosa, CA, USA ; Eastern Regional
Research Center, ARS, USDA, Wyndmoor, PA, USA; Department of Pathology, Miami
Children's Hospital, Miami, FL 33155, USA
BMC Complementary and Alternative Medicine 2011, 11:59
• Method (Part I):
Healthy human blood samples incubated with increasing
doses of MCP and antibodies.
At 24 hours samples lyzed and run on a flow cytometer.
Analyzed % of activated T-cytotoxic cell subset, B-
cells, and NK-cells; and % increase over untreated control.

35. Results Part I:
MCP Activates T-Cytotoxicity13
160%
* p < 0.05 **
Increase in T-Cytotoxic Cell Activation(%)
140% ** p < 0.01
120%
* *
100%
80%
60%
40%
20%
0%
MCP MCP MCP MCP MCP CD2/CD2R PMA
50 100 200 400 800 20 10
ug/ml ug/ml ug/ml ug/ml ug/ml ul/ml ng/ml

36. Results Part I:
MCP Increases B-Cell Activation13
1200% ***
1000% ** p<0.010
**
Increased B-Cell Activation (%)
*** p<0.001
800%
600%
400%
200%
0%
MCP MCP MCP MCP MCP MCP MCP PWM PWM
10 20 50 100 200 400 800 10 25
ug/ml ug/ml ug/ml ug/ml ug/ml ug/ml ug/ml ug/ml ug/ml

37. Results Part I:
MCP Increases NK Cell Activation13
1000% **
900%
Increased NK-Cell Activation (%)
800%
700% **
600%
500%
400% * *
300%
200%
100%
0%
MCP MCP MCP MCP MCP MCP MCP IL-2 IL-2
10 20 50 100 200 400 800 3.3 6.6
ug/ml ug/ml ug/ml ug/ml ug/ml ug/ml ug/ml ng/ml ng/ml

38. MCP: Induction of NK-Cell Activity Against
K562 Chronic Myeloid Leukemia Cells13
• Method (Part II):
NK cell ability to induce leukemia cell death
analyzed by co-incubating MCP-treated
lymphocytes with K562 T-cell leukemia cells.
Healthy human lymphocyte samples treated with
increasing doses of MCP. After 24 hours, K562
labeled. Plates returned to incubator (for 4 hrs) to
induce leukemia cell death.

39. Results Part II:
MCP Induces NK Cell Activity13
60%
(% K562 cell death over untreated WBC)
50%
Increase in NK Cell Activity
40%
30%
20%
10%
0%
MCP MCP MCP MCP MCP MCP MCP
10 20 50 100 200 400 800
ug/ml ug/ml ug/ml ug/ml ug/ml ug/ml ug/ml

40. MCP Immune System Benefits
• Induces NK Cell Activation
• Induces NK Cell Activity
• Activates T Cell Cytotoxicity
• Increases B Cell Activation

41. Modified Citrus Pectin:
Chelation &
Detoxification Research

42. MCP Heavy Metal
Elimination14
• Forms stacked “egg
box” structure
• Each pocket negatively
charged
• Negative charge binds
heavy metals
• Toxic metal trapped in
the “egg box”
• Safely excreted from
the body

43. The Effect of Modified Citrus Pectin on
Urinary Excretion of Toxic Elements14
Eliaz I, Hotchkiss AT, Fishman ML, Rode D; Amitabha Medical Clinic & Healing
Center, Sebastopol, CA, USA; Eastern Regional Research
Center, ARS, USDA, Wyndmoor, PA, USA; University of California, Davis, CA, USA ;
Phytother Res. 2006 20(10):859-64
• Methods: MCP administered for 6 days. Baseline 24 hr
urine collection before MCP, and on days 1 and 6.
Days 1 - 5: MCP 15 g/day & Day 6: MCP 20 g/day.
• Results: Urinary excretion of lead, mercury, cadmium
& arsenic increased. Essential minerals not changed.
No side effects reported.

44. The Effect of Modified Citrus Pectin on
Urinary Excretion of Toxic Elements14
Day-1 Day-6
450%
#
400%
* p < .05
# p < .10
350%
% Change from Day Zero
300%
250%
200%
150%
#
100%
50% * #
* * #
0%
Al… Sb… As… CD… Pb… Hg… Sn…

45. MCP & Urinary Excretion of Toxins14
MCP Chelation:
• Increased urinary excretion of toxic metals
• Demonstrated heavy metal chelation due
to reduced molecular size & esterification
• 10% rhamnogalacturonan II -- known for
binding affinity and immune enhancement
• Does not affect essential minerals
• No side effects reported

46. Modified Citrus Pectin Decreases
Total Mercury Body Burden:
Pilot Human Clinical Trial15
Eliaz I, Amitabha Medical Clinic & Healing Center, Sebastopol, California, USA
EcoNugenics, Santa Rosa, California, USA 228th ACS National Meeting,
Philadelphia PA. 2004
• Method: 5g MCP 3x/day; 4-10 months. Baseline
and final total mercury body burden measured
using IV DMPS challenge.
• Results: All subjects showed significant decrease
in mercury levels. Avg decrease: 62.17%
(p=0.03). No side effects reported.

47. Mercury Body Burden Results15
ug Mercury /g Creatinine
Percent
Duration of
Patient Post Change in
Baseline Difference Intervention
Number Intervention Mercury
(months)
Burden
Patient 1 14 4.5 9.5 67.86% 10.0
Patient 2 180 49.0 131 72.78% 4.5
Patient 3 16 9.9 6.1 38.13% 4.0
Patient 4 29 7.3 21.7 74.83% 6.5
Patient 5 22 9.4 12.6 57.27% 6.5

48. Mercury Body Burden Study15
• Results: MCP
decreased total % Mercury Reduction from Baseline
body burden in all
subjects 80%
70% 67.90%
72.80% 74.80%
– Average decrease 60% 57.30%
62.17%
62.17% (p=0.03) 50%
38.10%
40%
• MCP is a promising 30%
20%
systemic chelator 10%
of heavy metals 0%
that can be used on Patient
1
Patient
2
Patient
3
Patient
4
Patient
5
Avg
an ongoing basis 10 mo 4.5 mo 4 mo 6 mo 6.5 mo

49. The Role of Modified Citrus
Pectin as an Effective
Chelator of Lead in
Children Hospitalized with
Toxic Lead Levels16
Zhao ZY, Liang L, Fan X, Yu Z, Hotchkiss AT, Wilk BJ, Eliaz I
Children’s Hospital, Zhejiang University, School of
Medicine, Hangzhou, Republic of China, Centrax
International, Inc, San Francisco, California, USA
Eastern Regional Research
Center, ARS, USDA, Wyndmoor, Pennsylvania, USA
EcoNugenics, Santa Rosa, California, USA
Altern Ther Health Med. 2008 14(4):34-8

50. Lead in Blood Serum16
60
Before After
Blood Serum Lead Concentration (ug/dL)
MCP MCP
50
40
30
20
10
0
Patient-1 Patient-2 Patient-3 Patient-4 Patient-5 Patient-6 Patient-7
(MCP 5 grams, 3 times daily) P Value = 0.0016

51. Lead in 24 Hour Urine Excretion16
140
Before After
MCP MCP
120
100
Lead Levels (mcg/dL)
80
60
40
20
0
Patient-1 Patient-2 Patient-3 Patient-4 Patient-5 Patient-6 Patient-7
(MCP 5 grams, 3 times daily) P Value = 0.0007

52. Summary: Benefits of
Modified Citrus Pectin
• Galectin-3 Blocker
• Anti-Cancer
• Immunity
• Chelation and Detox

53. Research: Synergistic Benefits of MCP
w/Botanical Formulas

54. Prostate Poly Botanical Formula
Integrative blend of
33 ingredients:
Vitamins, Minerals,
Botanically Enhanced
Medicinal Mushrooms,
and Botanical Extracts

55. ProstaCaid

56. ProstaCaid Induces G2/M Cell Cycle Arrest & Apoptosis
in Human & Mouse Androgen-Dependent & -
Independent Prostate Cancer Cells 17
Yan J & Katz AE; Department of Urology, Columbia University Medical Center, New York, NY, USA.
Integr Cancer Ther 2010 9:186-196
Effects on cell viability on androgen- Effects on long-term cell viability by colony
dependent, LNCaP (A) & CASP 2.1 (C), & androgen- formation
independent PC3 (B) & CASP 1.1 (D)

57. Suppression of Growth and Invasive Behavior
of Human Prostate Cancer Cells by ProstaCaid:
Mechanism of Activity18
Jiang, J, Eliaz, I, and Sliva, D; Cancer Research Laboratory, Methodist Research
Institute, Indianapolis, IN,USA ; Amitabha Medical Clinic & Healing
Center, Sebastopol, CA, USA
Indiana Univer. Cancer Center, Indiana Univer. School of Med., Indianapolis, IN, USA
Int J Oncol. 2011 Jun;38(6):1675-82
120 0 g/ml
10 g/ml
20 g/ml
100
Proliferation Index (%)
40 g/ml
* 80 g/ml
*
80 * *
*
*
60
*
*
40 *
*
20 *
0
24 hours 48 hours 72 hours

58. Effect of ProstaCaid on Invasive Behavior
of Prostate Cancer Cells18
120 120
Cell migration [%]
Cell adhesion [%]
100 100
80 * 80 *
60 60
* *
40 40
20 20
0 0
0 20 40 80 0 20 40 80
ProstaCaid (g/ml) ProstaCaid [g/ml]
120
Cell invasion [%]
100
*
80
*
60
40
20
0 
0 20 40 80
ProstaCaid [g/ml]

59. Study Highlights18
•

60. ProstaCaid Inhibits Tumor Growth in a
Xenograft Model of Human Prostate Cancer19
Jiang J, Loganathan J, Eliaz I, Terry C, Sandusky GE, Sliva D; Cancer Research
Laboratory, MRI, Indiana University Health, Indianapolis, IN, USA; Amitabha Medical
Clinic and Healing Center, Sebastopol, CA, USA; Indiana University. Simon Cancer
Center, Indiana University. School of Med., Indianapolis, IN, USA, Intern J of Oncol 2012;
Doi:10.3892/ijo.2012.1344
• Method: ProstaCaid in xenograft model of
human hormone refractory PC3 prostate
cancer - (100, 200 and 400 mg/kg)

61. ProstaCaid Inhibits Tumor Growth in a
Xenograft Model of Human Prostate Cancer19
Results:
No effect on body weight or activity of liver enzymes (ALT, AST)
No sign of toxicity in liver, spleen, kidney, lung and heart tissues
in mice
Inhibition of tumor volumes (1024.6 378.6 vs.
749.3 234.3, P<0.001)
qRT-PCR analysis demonstrated significant up regulation of
expression of CDKN1A (p21) and inhibition of expression of
IGF2, NR2F2 and PLAU (uPA)
Conclusion: ProstaCaid has significant anticancer activity in vivo
with no signs of toxicity.

62. Breast Poly Botanical Formula
Contains
botanicals, purified
biologically active
nutritional compounds and
botanically enhanced
medicinal mushrooms

63. BreastDefend

64. Suppression of Proliferation & Invasive
Behavior of Human Metastatic Breast Cancer
Cells by Dietary Supplement BreastDefend20
Jiang J, Wojnowski R, Jedinak A, Sliva D; Cancer Research Laboratory, Methodist Research
Institute, Indianapolis, IN, USA Department of Medicine, Indiana University. Cancer
Center, School of Med., Indiana University, Indianapolis, IN, USA; Integr Cancer Ther.
2011; Jun 10 (2):192 – 200
0g/ml
120 10 g/ml
20 g/ml
30 g/ml
100
40 g/ml
Proliferation Index [%]
80
* *
60
* *
*
40
*
20
* * * *
0
24 hours 48 hours 72 hours

65. BreastDefend Suppresses MDA-MB-231
Growth and Breast-to-Lung Metastasis in
Tumor Model (Pre-Published Data)
• Method: Human breast cancer cells (MDA-MB-231)
implanted into the mammary gland in mice
Pre-Published Results: BreastDefend significantly
decreased tumor volume and breast-to-lung metastasis
in highly aggressive triple negative breast cancer, without
toxicity.

66. Synergistic and Additive Effects of
Modified Citrus Pectin with Two Novel
Poly Botanical Compounds, in the
Suppression of Invasive Behavior of
Human Breast and Prostate Cancer
Cells21
Jiang J, Eliaz I, and Sliva D
Cancer Research Laboratory, MRI, Indiana University
Health, Indianapolis, IN, USA
Amitabha Medical Clinic & Healing Center, Sebastopol, CA, USA
Depart. of Med., and Indiana Univer. Cancer Center, Indiana
Univer. School of Med., Indianapolis, IN, USA.
Integr Cancer Ther. 2012 (In Press)

67. Proliferation Index (%) . ProstaCaid21

68. ProstaCaid & MCP21
120
100
80 P<0.01
% Migration
P<0.01
60
40 P<0.01
20
0
MCP 0 0.25 0.5 1.0 0 0.25 0.5 1.0 mg/ml
ProstaCaid 10 10 10 10 g/ml

69. BreastDefend21
120
Proliferation Index (%)
100
80
60
40
20
0
0 5 10 20 40

70. BreastDefend & MCP21
120
100
P<0.01
80
% Migration
P<0.01
60
P<0.01
40
20
0
MCP 0 0.25 0.5 1.0 0 0.25 0.5 1.0 mg/ml
BreastDefend 20 20 20 20 g/ml

71. Honokiol
• Honokiol is a small-molecule polyphenol isolated from
the genus Magnolia officinalis (Hou Po)
• Properties
• Anti-Tumor
• Anti-Angiogenic
• Anti-Inflammatory
• Anti-Anxiety
• Antioxidant
• Selective Pro-Oxidant
• Differentiation Agent
• No Appreciable Toxicity
• Synergistic Anticancer Effect w/ Multiple Chemotherapy
Drugs

72. Honokiol
Mechanisms of Action
• Modulation of GABA receptors
• Blocks signaling in tumors with defective p53 function
and activated ras by blocking activation of
phospholipase D.
• Induces cyclophilin D, potentiating mitochondrial
permeability transition pore and causing death in cells
with wild-type p53.
• MTOR-1 Inhibitor

73. Selected Honokiol Cancer Research22,23,24
• Honokiol traverses the blood-brain barrier and induces
apoptosis of neuroblastoma cells via an intrinsic bax-
mitochondrion-cytochrome c-caspase protease pathway. Lin
JW, Chen JT, Hong CY, et al. Neuro Oncol. 2012 Jan 18.
• Antimetastatic activity of honokiol in osteosarcoma.
Steinmann P, Walters DK, E Arlt MJ, et al. Cancer. 2011 Sep 20.
doi: 10.1002/cncr.26434.
• Honokiol arrests cell cycle, induces apoptosis, and potentiates
the cytotoxic effect of gemcitabine in human pancreatic
cancer cells. Arora S, Bhardwaj A, Srivastava SK, et al. PLoS
One. 2011;6(6):e21573.

74. Selected Honokiol Cancer Research25,26,27
• Honokiol produces anti-neoplastic effects on melanoma cells
in vitro. Mannal PW, Schneider J, Tangada A, et al. J Surg
Oncol. 2011 Sep 1;104(3):260-4.
• Honokiol radiosensitizes colorectal cancer cells: enhanced
activity in cells with mismatch repair defects. He
Z, Subramaniam D, Ramalingam S, Dhar A, et al. Am J Physiol
Gastrointest Liver Physiol. 2011 Nov;301(5):G929-37.
• Honokiol: a promising small molecular weight natural agent
for the growth inhibition of oral squamous cell carcinoma
cells. Chen XR, Lu R, Dan HX, et al. Int J Oral Sci. 2011
Jan;3(1):34-42.

75. Selected Honokiol Cancer Research28,29,30
• Apoptosis induced by Magnolia Grandiflora extract in
chlorambucil-resistant B-chronic lymphocytic leukemia cells.
Marin GH, Mansilla E. J Cancer Res Ther. 2010 Oct-Dec;6(4):463-5.
• Modulation of multidrug resistance p-glycoprotein activity by
flavonoids and honokiol in human doxorubicin- resistant sarcoma
cells (MES-SA/DX-5): implications for natural sedatives as
chemosensitizing agents in cancer therapy. Angelini A, Di Ilio
C, Castellani ML, et al. J Biol Regul Homeost Agents. 2010 Apr-
Jun;24(2):197-205.
• Honokiol induces paraptosis and apoptosis and exhibits schedule-
dependent synergy in combination with imatinib in human
leukemia cells. Wang Y, Yang Z, Zhao X. Toxicol Mech Methods.
2010 Jun;20(5):234-41.

76. Effect of HonoPure (98% Honokiol) on
Growth of PC3 Cells (Pre-Published data)
120 0 
5 
10 
100
Proliferation Index (%)
20 
* 40 
*
80
*
60 *
*
40
*
20
*
*
0
24 hours 48 hours 72 hours

77. Effect of HonoPure (98% Honokiol) on
the Growth of MDA-MB-231 Cells
(Pre-Published Data)
120 0 
5 
10 
100
Proliferation Index (%)
20 
* 40 
80
*
*
60
40 *
*
*
20
*
0
24 hours 48 hours 72 hours

78. Synergistic Effect of PectaSol-C MCP &
HonoPure (98% Honokiol) on PC3 Cell line
Migration (Pre-Published Data)

79. Honokiol Clinical Use and Dosages
• Active Cancer
1,000 mg x 3/day, with food
• Prevention and Post-Therapy
1000 mg /day, with food
• Anti-Inflammatory and Circulation Support
500 mg – 1,000 mg daily, with food
• Anxiety and Insomnia
250 – 500 mg daily, with food

80. Galectin-3
Breakthrough Research

81. Galectin-3 Levels & Mortality from All Causes
in the General Population: PREVEND1
100% Median
Galectin-3
Cumulative Survival Rate (%)
Levels
Quintile-1
95% 7.7
Quintile-2
9.4
90% Quintile-3
10.9
Quintile-4
12.6
85% Quintile-5
Start
Year-5
Year-1
Year-2
Year-3
Year-4
Year-6
Year-7
Year-8
Year-9
Year-10
Year-11
15.6
Overall
Average
Number of Subjects n = 7,968 11.9

82. Galectin-3 in General Population:
PREVEND (number of subjects = 7,968) 1
CHARACTERISTIC TOTAL QUINTILE-1 QUINTILE-2 QUINTILE-3 QUINTILE-4 QUINTILE-5 P
Median Gal3 11.9 7.7 9.4 10.9 12.6 15.6
DM% 3.6 2.3 2.3 3.1 4.3 6.1 0.000
MI 3.7 1.8 2.4 2.7 4.2 7.4 0.000
Hypertension 33.4 22.2 26.6 31.1 39.7 47.9 0.000
Stroke % 0.9 0.8 0.6 0.6 1.3 1.6 0.004
Systolic BP 129.2 20.2 125.0 18.1 126.6 19.0 128.6 19.6 131.3 20.6 134.9 22.5 0.000
Diastolic BP 74.0 9.7 72.1 9.4 73.3 9.8 74.1 9.6 75.2 9.8 75.4 9.8 0.000

83. Galectin-3 in General Population:
PREVEND (number of subjects = 7,968) 1
CHARACTERISTIC TOTAL QUINTILE-1 QUINTILE-2 QUINTILE-3 QUINTILE-4 QUINTILE-5 P
Median Gal3 11.9 7.7 9.4 10.9 12.6 15.6
1.29 0.89 1.04 1.33 1.53 1.98
CRP 0.000
[0.56-3.00] [0.39-2.16] [0.49-2.40] [0.58-2.92] [0.71-3.42] [0.85-4.28]
Cholesterol 5.66 1.12 5.41 1.05 5.56 1.10 5.68 1.11 5.79 1.11 5.91 1.17 0.000
LDL 3.69 1.05 3.47 1.00 3.60 1.01 3.71 1.04 3.77 1.05 3.90 1.06 0.000
1.27 1.32 1.28 1.25 1.24 1.24
HDL 0.000
[1.03+1.56] [1.07-1.62] [1.04-1.57] [1.03+1.55] [1.03-1.53] [0.99-1.52]
1.16 1.02 1.11 1.17 1.23 1.31
Triglycerides 0.000
[0.85-1.68] [0.75-1.43] [0.82-1.59] [0.86-1.69] [0.89-1.78] [0.95-1.92]

84. COACH Galectin-3 Sub-Study
Mortality from All Causes at 1 Year
in Patients with CHF31
40%
36.51%
35%
% Died within 365 Days
30%
25%
19.69%
20%
15% 12.57%
10%
5%
0%
< 17.8 17.8 - 25.9 > 25.9
Galectin-3 Levels (ng/mL)

85. Research: Elevated Galectin-3 Implicated in a
Wide Variety of Disease States
• Cardiovascular Diseases32
Elevated Galectin-3 linked with inflammation, heightened
fibrosis, heart failure, coronary artery disease, peripheral artery
disease, strokes, and vascular dementia.
• Liver Disease33,34
Elevated Galectin-3 linked with extensive fibrosis of the liver.
Reducing Galectin-3 resulted in improved hepatic health, including
reduced inflammation, hepatocyte injury and fibrosis.
• Gastrointestinal Conditions 35
Reducing Galectin-3 resulted in reduced inflammation in the gut
mucosa -- important for treatment of ulcerative colitis, non-specific
colitis, Crohn’s disease, Celiac disease and gluten sensitivity.
• Type 2 Diabetes & Similar Metabolic Diseases36
Reducing Galectin-3 reduced inflammation in these conditions.

86. Modified Citrus Pectin
Reduces Galectin-3
Expression and Disease
Severity in Experimental
Acute Kidney Injury37

87. MCP & Kidney Injury Study37
Background: Folic acid (FA)-induced acute kidney injury model.
Method: Mice given 1% MCP-supplemented water, or plain water, 1
week before FA injection.
Results: During initial injury phase, all FA treated mice lost weight while
their kidneys enlarged secondary to renal insult.
• Gross changes significantly lessened in MCP group.
• MCP clearly reduced renal cell proliferation.
• Recovery phase:
MCP group showed decreased Galectin-3 expression with
decreased renal fibrosis, macrophages, pro-inflammatory cytokine
expression, and apoptosis.

88. Serum Galectin-3
Testing
FDA approved blood test measures
Circulating Galectin-3 for
Cardiovascular Disease

89. Elevated Galectin-3:
What can we do?
• Test for Galectin-3 levels
• Address general inflammation & hyper
viscosity
• Use MCP at appropriate dosages by:
• Condition
• Galectin-3 levels
• Therapeutic goal

90. Galectin-3 Levels: Reference Ranges
• Galectin-3 levels > 17.8 ng/ml are considered to be an
extreme risk factor of mortality.
• Ideal levels are < 14 ng/ml in the
general population.
• For cancer and cardiac patients,
ideal levels are < 12 ng/ml.
• Galectin-3 levels change in 20% of population every 3
months.
• Repeated testing is important.

91. Galectin-3 Levels: MCP Dosage
Active Cancer
• Levels <17.8
MCP 15g daily
• Levels >17.8
MCP 20 - 25g daily

92. Galectin-3 Levels: MCP Dosage
•
•
•
•

93. In Conclusion
• Galectin-3 plays an important role in
prevention, treatment and prognosis
of multiple medical conditions
including cancer.
• MCP is an effective natural Galectin-3
blocker.

94. Thank you!
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ieliaz@sonic. net
www.dreliaz.org