Curcumin: The All-In-One Solution

This is Turmeric: Curcuma longa

Turmeric origins

• Native to southern Asia

• Extensively used throughout all of Asia as

food and medicine

Traditional Use

• Food

• Cosmetic

• Medicine

• Color

Even Religious Applications

Turmeric is one of the primary plants used to dye the robes of Buddhist Monks

Powerful Pigment

• Lends distinctive yellow color to curry

• Also used to color butter, cheese, mustard,

and other foods

Traditional Medicine

Ayurveda

• lung disorders

• asthma

• coughs

• allergy

• sinusitis

• liver disorders

• rheumatism

• diabetic wounds

Turmeric & Curcumin: What’s the Difference?

Turmeric Plants in India

Curcumin Powder

Fresh Turmeric Root

Only 2 to 5% of turmeric

is curcumin. Turmeric is

the healthy food, but

curcumin is the natural

medicine.

What are Curcuminoids?

• Active compounds in turmeric

– 3-5% of turmeric is cucuminoids

– Natural curcumin contains all 3 curcuminoids in

the same ratio at which it occurs in the plant

The Many Uses for Curcumin

What Makes Curcumin So Useful?

• Potent Antioxidant – Can also increase activity of protective glutathione

• Anti-inflammatory – Suppresses the activation of the NF-kB

– Downregulates COX-2

– Inhibits 5-LOX

– Downregulates the expression of cell surface adhesion molecules

linked to inflammation

– Inhibits the activity of pro-inflammatory cytokine TNF

• Anti-Cancer – Kills tumor cells

– Modulates tumor growth cell factors

Curcumin Exhibits Chemoprotective Effects Against Cancer

• Gastrointestinal Cancers – Colon cancer, colitis, ulcerative colitis, duodenal tumor,

esophageal cancer, stomach cancer

• Liver cancer

• Lung cancer

• Blood cancer

• Breast cancer

• Oral cancer

• Prostate cancer

• Skin cancer

• Multi-organ cancer

Epigenetics: Are My Genes My Destiny?

Epigenetics and Cancer Prevention through the Diet • Epigenetics - mechanisms that exert an heritable and

INDIRECT influence on gene expression that do NOT

involve a permanent change in DNA expression

• In contrast to genetic alterations, epigenetic changes

– Occur much earlier during cancer initiation and progression

– Are potentially reversible

– Are easily influenced by dietary and environmental factors

(meat, fat, smoking, alcohol, etc.)

Since humans are genetically very similar, it

is believed that ‘epigenetic’ mechanisms

may play a more important role in modifying

disease risks, including cancer.

Epigenetic Changes: Reawakening Sleeping Genes

Reversal of Epigenetic Alterations by Natural Compounds

Curcumin Cancer Research

Curcumin Induces Epigenetic Changes in Cancer Cells

Curcumin modulates DNA methylation in colorectal

cancer cells

Link A, Balaguer F, Shen Y, Lozano JJ, Leung HE, Boland CR and Goel A

PLoS One (In Press), 2013.

Conclusions: This study provided previously unrecognized

evidence for curcumin-mediated DNA methylation alterations

as a potential mechanism of colon cancer chemoprevention.

In contrast to non-specific hypomethylating agents, curcumin-

induced methylation changes occurred only in a selected

subset of cancer-related genes.

Control

5-Aza (DNMTi)

β-v

alu

e

5-Aza

TSA (HDACi)

β-v

alu

e

TSA

1.0

0.5

0.0

1.0

0.5

0.0

27,000 CpG loci

β-v

alu

e

β-v

alu

e

β-v

alu

e

1.0

0.5

0.0

Curcumin-STC (6 d)

Curcumin-LTC (240 d) HCT116

RKO

HT29

1.0

0.5

0.0

1.0

0.5

0.0

Curcumin Reactivates Sleeping Genes and Kills Cancer Cells

77

48 158

109

Fo

ld c

ha

ng

e (

Ge

ne

ex

pre

ss

ion

)

Δβ-value (DNA methylation)

HCT116

355

322 208

162

Δβ-value (DNA methylation)

Fo

ld c

ha

ng

e (

Ge

ne

exp

ress

ion

) HT29

24

15

84

73

Fo

ld c

ha

ng

e (

Ge

ne

exp

ress

ion

)

Δβ-value (DNA methylation)

RKO

1607

986

Δβ-value (DNA methylation)

Fo

ld c

ha

ng

e (

Ge

ne

ex

pre

ss

ion

) RKO 5-Aza

Curcumin Induces Both Hypo- and Hyper-Methylation Of Genes in CRC Cells

Oncogenes-Hyper-

methylated and Silenced?

Tumor Suppressor

Genes-Hypomethylated & Re-expressed

Overexpression of Oncogenes

HER2

Growth factors

(e.g; EGF, PDGF, FGF)

Growth factor receptors

Survival factors

(e.g; Survivin,Bcl-2 and Bcl-xl)

Cyclin D1

Decoy receptor

Overexpression of Matrix metalloproteases

Cyclooxygenase-2

Adhesion molecules

Chemokine

TNF

Proliferation Invasion

Tumor

Metastasis

Normal

cells

Tumor

cells

Transformation

Tumor

growth

Constitutive activation of

transcription factors AP-1& NF-kB

Curcumin

Different Stages of Cancer Progression: Suppression by Curcumin

Curcumin Sensitizes Cancer Cells to Chemotherapy

Curcumin enhances the effect of chemotherapy against

colorectal cancer cells by inhibition of NF-κB and Src

protein kinase signaling pathways

M Shakibaei, A Mobasheri, C Lueders, F Busch, P Shayan and A Goel

PLoS One (In Press), 2013.

Conclusions: Combining curcumin with conventional

chemotherapeutic agents such as 5-FU could provide more

effective treatment strategies against chemoresistant colon

cancer cells. The mechanisms involved may be mediated via

NF-κB/PI-3K/Src pathways and NF-κB regulated gene

products.

Curcumin pre-treatment re-sensitizes 5-FU treated colon cancer cells

Individual

treatments with

curcumin and 5-FU

Pre-treatment with

curcumin

Making Cancer Treatments Better?

• Curcumin is a chemosensitizer and

radiosensitizer for tumors

AND SIMULTANEOUSLY

• protects normal organs such as liver,

kidney, oral mucosa, and heart from

chemotherapy and radiotherapy-induced

toxicity Curcumin increases the activity of antioxidant

enzymes such as glutathione peroxidase and

directly quenches free radicals

Chemotherapy That May Require Caution

Cyclophosphamides (in animal studies, protected against chemo injury but may reduce chemo effectiveness

Adriamycin (doxorubicin) due to a competitive interaction at the JNK pathway (curcumin inhibits, normally a good think in cancer cells, but Adriamycin requires this pathway for efficacy). Always involve your healthcare

practitioner in the discussion of

whether supplements are right for you

during cancer treatment

RECENT CURCUMIN RESEARCH

other conditions

New Research on Rheumatoid Arthritis

• 45 patients with RA

– High absorption curcumin (500 mg)

– Diclofenac sodium (50 mg)

– Curcumin plus diclofenac (500 + 50)

• Goal: obtain a reduction in the Disease

Activity Score 28 (DAS 28)

– DAS 28: combines different measurements of RA

disease activity into a single index (tender joints,

swollen joints, general health assessment, etc)

• Length of study: 8 weeks

• Published in Phytotherapy Research March

2012

Study Results: DAS 28 Score

-44.5%

-44.4% -42.1%

The analysis was within the group. Independent t-test was used.

Boswellia

Boswellia

• Frankincense

– Resin from the boswellia tree

• Aroma from the resin has been

valued since the time of the

ancient Egyptians

– Perfumes and incense

• Ayurvedic medicine

(traditional use)

– Arthritis

– Coughs and asthma

– Colitis

– Sores

– snakebites

How Does it Work?

• Boswellic acids – key active compounds

• Potent inhibitors of inflammatory compounds

– 5-lipoxygenase (5-LOX)

• Cytotoxic

– Promotes cell death in cancer cells, without

harming healthy cells

• Active compounds – boswellic acids

Boswellic acids

• Most boswellic acids have anti-inflammatory activity – Acetyl-α-Boswellic Acid

– Acetyl-β-Boswellic Acid

Acetyl-11-keto-β-Boswellic Acid (AKBA)

• AKBA = most potent inflammation inhibitor • Also inhibits activators that promote tumor cell growth

• Beta boswellic acid promotes inflammation • Removal from boswellia yields a more powerful

extract. Highest quality boswellia is standardized for less than 5% beta boswellic acid content.

Key Compound: AKBA

• Like curcumin, AKBA has ability to reverse

epigenetic changes leading to cancer

AKBA Restores Expression of TSGs

AKBA Inhibits DNMT Activity in Cancer Cells

Points in Boswellia Standardization

• Boswellia has greatly varying amounts of

AKBA, and can contain as little as 1-2%

• Look for more than 10% naturally occurring

AKBA (not spiked)

• Screen/purify for pro-inflammatory beta

boswellic acid (BBA) for best effects. Should

be less than 5% content

• Clinically studied extracts with data on human

use

Curcumin and Boswellia: Chemoprotective Effects