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A rational approach to helping cancer patients with natural therapies - Dr William Barnes MbChb Bsc (otago)\nFACNEM

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Natural therapies and cancer

Natural therapies and cancer

A rational approach to helping cancer patients with natural therapies

Dr William Barnes MbChbBsc (otago)


Chemotherapy success in cancer
Chemotherapy success in cancer

  • According to a recent analysis of 5 year surviaval rates in cancer patients following chemotherapy, oncology has done little to cure cancer . val

  • Chemotherapy as a stand alone treatment provided a 23% overall cure rate for adult solid tumours.

    Ref:The contribution of cytoxic chemotherapy to 5 year survival in adult malignancies,

    Morton. al Clinical oncology (2004)16 ;549-

Inflammation and cancer
Inflammation and cancer

  • Why is inflammation so important in cancer ?

    Because it drives :

  • 1 mitosis

  • 2 metastasis

  • 3 angiogenesis


  • The process of neovasclarisation is controlled in normal tissues by a sequence of endogenous polypeptides that are secreted during growth, healing and tissue renewal.

  • Neoplasms are able to synthesize or induce some of these polypeptides.In particular Vascular endothelial growth factor (VEGF) and angiopoietins (APNS)


  • All tumours have relative hypoxia, tumours outgrow their blood supply once they form masses greater than 1-2mm

  • Tumours do not grow progressively unless they induce blood supply from the surrounding stroma.

Inflammation and cancer1
Inflammation and cancer

  • How:

  • Induction of cytokines :

  • NF Kappa

  • TNF alpha

  • Cox

  • Interleukins IL 1 IL6 IL 8

  • VEGF

  • NO

Angiogenesis and inflammation
Angiogenesis and inflammation

  • Cytokines involved in induction of angiogenesis:

  • TNF alpha

  • Cox 2/ Lox

  • IL8

  • NOS

Host derived factors
Host derived factors

Innate immune system cells such as macrophages (TAMS)produce cytokines :

  • NF Kappa , TNF alpha, NO, IL8.


  • Producing, Fibroblast growth factor(FGF-1 and FGF-2 or bFGF) of which bFGF is the most potent.

Source of drivers for angiogenesis
Source of drivers for angiogenesis

Tumour derived factors:

  • VEGF, anti angiopoietins are produced by hypoxic tumours

  • bFGF, Cox ,Lox, are up regulated genetically and screted by many; Squamous produces high levels of Cox and Lox.

    Ca bowel is noted for Cox production

  • The tumour therefore can regulate its own rate of angiogenesis.

High expression of hifa is a predictor of outcome in pancreatic cancer
High Expression of HIFa is a predictor of outcome in pancreatic cancer

  • Hypoxic intrinsic factor ( HIF).is a signalling molecule that up regulates VEGF

Radiotherapy pancreatic cancer

  • There is clear evidence whilst radiotherapy is a powerful antimitotic it also creates inflammation and as such angiogenesis:

  • During radiotherapy tumours increase there angiogenic potential.

  • Combination of antiangiogenic agents and radiotherapy is more effective:

  • AnsiauxR, Baudeletet al Clin Cancer Res 200511:743-50

  • Koukourakis MI et al anticancer Res 2001:21 4301-9

Chemotherapy pancreatic cancer

  • “ NF KAPPA is a resistance factor to Platinum based Antineoplastic Drugs – new aproaches focusing on inhibition of this factor could help to minimize or even eliminate resistance to platinum drugs”

  • Vilma Maldonado Laguns and Jorge Melendez-Zajgla.

  • Hindawi Publishing Corporation

  • Metal Based Drugs Vol 2008

Supporting the cancer patient
Supporting the cancer patient pancreatic cancer

A sensible program to provide support to the cancer patient should include treatments that suppress :

  • Angiogenesis

  • Mitosis

  • Metastatic spread

    Deal with all of these 3 factors and results will be much better

Nutritional substances
Nutritional substances pancreatic cancer

  • Overwhelming evidence exists in the literature showing that natural substances, in particular polyphenols, flavonoids, minerals and vitamins decrease, inflammation angiogenesis and metastasis by decreasing:

  • Cox ,Lox ,Nf kappa, IL1 ,IL8 ,TNF alpha, bFGF, VEGF .

Genistein sensitises lymphoma to chop
Genistein sensitises lymphoma to CHOP pancreatic cancer

  • Vivo study : Diffuse large cell lymphoma which are notable for high expression of NK Kappa

  • High NF Kappa thought to increase the resistance of these cells to CHOP (cyclophosphamide, doxorubicin,vincristine, and prednisolone)

  • Genistein enhanced the growth inhibitory effects of the chemotherapy

  • Mol cancer ther 203Dec2(12):1361-8

Inhibition of cell growth and vegf in ovarian cancer cells by flavonoids
Inhibition of cell growth and VEGF in ovarian cancer cells by flavonoids

  • In vitro study on OVCAR cells( ovarian Cancer)

  • Six flavonoids including: apigenin, luteolin, quercetin, genistein,and kaempferol were shown to inhibit cancer cell growth.

  • The rank of VEGF inhibition:

  • Genistein>kaempferol>apigenin>quercetin >luteolin>cysplatin.

  • Nutr cancer 2008:60(6):800-9

Tamoxifen in oestrogen negative breast cancer
Tamoxifen in Oestrogen negative breast cancer by flavonoids

  • In vivo:

  • Realistic doses of Tamoxifen can suppress the growth of ER-negative breast cancer when combined with EGCG.

  • This is achieved by a decrease in mTOR ( a signalling molecule for angiogenesis) and EGF in the tumour

  • Br J Cancer 2008 Oct 7:99 (1056-63)

6 gingerol inhibits angiogenesis
6-Gingerol inhibits angiogenesis by flavonoids

  • In vitro and In vivo study;

  • study using melanoma cell line:

  • Anti-angiogenic activity was noted in vitro by inhibiting endothelial response to VEGF and bFGF.

  • In Vivo reduced numbers of lung metastasis were noted in treated animals.

  • Biochem Biophys Res Commun 2005Sep23;335(2):300-8

Dose ranges of phytochemicals for angiogenesis inhibition
Dose Ranges of Phytochemicals for angiogenesis inhibition by flavonoids


Cancer adjuvant dose

1000-2500mg 3x daily

1000-2500mg 3x daily

600-1000mg 3xdaily

500-1500mg 3x daily

2000mg 3x daily

  • Curcumin

  • Green Tea

  • Grape seed extract

  • quercetin with bromelian

  • Silibinin

  • S.M Sagar MD D Yance MH and R.K.Wong MD

  • Current oncology – vol 13, Number 3

Modified citrus pectin mcp
Modified citrus Pectin( MCP) by flavonoids

  • MCP is a fractionated pectin obtained from the peel and pulp of citrus fruits

  • MCP is rich in galactosides giving it affinity for certain types of cancer cells.

  • These galactosides bind to the surface galectins on the cancer cells

  • This bind stops metastatic cells from clumping and as such adhering to endothelial cells and developing as metastasis

  • Dose for clinical use 6 -30gms

Mcp lead chelator
MCP Lead Chelator by flavonoids

  • MCP has been shown to chelate lead from children .

  • Trial involved children 5-12 with serum levels over 20micog/dL.

  • 15 gms 3x daily

    ..Dramatic reductions in serum lead were observed over one month .

  • This correlated with increases in urinary lead levels in 24 hr collections.

  • Altern ther health Med 2008 Jul-Aug ;14(6):18

Suppression of proinflammatory responses by mcp
Suppression of proinflammatory responses by MCP by flavonoids

  • 2006 study on effects of MCP on Macrophage function.

  • Investigations of LPS activated macrophages expression of iNOS and COX-2 was conducted in vitro.

  • MCP reduced iNOS ,COX-2, and NF Kappa expression significantly.

  • Biochem Pharmacol 2006 Oct 168): 1001-9

Oral mcp in breast carcinoma
Oral MCP in breast carcinoma by flavonoids

  • MCP given orally inhibits tumour growth angiogenesis and metastasis.i

  • in vivo

  • Studies in an athymic mouse model showed statistically reduced tumour growth and metastasis in mice given oral MCP

  • J Natl Cancer Inst 202 Dec 18;94(24:1854-62)

Mcp cancer
MCP Cancer by flavonoids

  • MCP has been shown to reduce metastasis angiogenesis, and tumour growth in :

  • Colon , breast , melanoma, prostate, lung,in both primary and metastatic cancers.

Vit d deficiency in breast cancer
Vit D deficiency in breast cancer by flavonoids

  • A Canadian study published in 2008 involving 512 women showed that 37.5% of women had Vit D lower than 50nmol/L at diagnosis. These women:

    * had more aggressive disease

    * were 93% more likely to develope metastasis

    *were 73% more likely to die than women with normal levels of vit D at diagnosis.

    In this country vit D deficiency particularly in the elderly may be an epidemic

    Medscape medical news 26/5/08

Vit d levels
Vit D levels by flavonoids

  • Vit D hydroxycalciferol nmol/L (50-150)

  • Mild deficiency 25-50 nmol/L

  • Mod deficiency 12.5-25 nmol/L

  • Severe deficincy <12.5 nmol/L

  • “Aus and NZ” MJA, 182(6): 281-285 2005

Abcg2 the key to cancer resistance in cancer stem cells
ABCG2 : the key to cancer resistance in cancer stem cells by flavonoids

  • Multi-drug resistance remains one of the most common reasons for chemotherapy failure.

  • The membrane transporter proteinABCG2/BCRP1 has been shown to reduce the intracellular concentrations of chemotherapy drugs such as; ironotecan and doxorubicin.

  • ABCG2 may be represented in greater amounts in cancer stem cells.

Abcg2 cont
ABCG2 cont by flavonoids

  • ABCG2 may underlie the ability of the cancer stem cell to start the regeneration of the tumour post chemotherapy.

  • Substances that inhibit ABCG2 may increase the chemosensitivity of cancer stem cells to chemotherapy and as such improve chemotherapy response;

  • An Y, Ongkeko WM, Expert Opin Drug Metab Toxicol Aug 27 2009

Combined effects of flavonoids on abcg2
Combined effects of flavonoids on ABCG2 by flavonoids

  • “ the added effects of multiple flavonoids for breast cancer resistant protein (ABCG2) inhibition .... Provides a rationale for using “flavonoid cocktails” as a potential aproach for multidrug resistance reversal in cancer treatment”

  • Zhang. S. et al ,Pharm Res 2004 Jul;21(7):1263-73

Abc transporter abcg2 is inhibited by quercetin
ABC transporter ABCG2 is inhibited by Quercetin by flavonoids

  • “ 20 umol of Quercetin was found to be the strongest inhibitor of ABCG2 in an in vitro study in HEK293 cells.”

  • 20umol can be achieved with 100mg Quercetin

  • May need less if used in synergy with other flavonoids

  • Yoshikawa M, et al,J exp ther oncol 2004 Apr:4(1) :25-35