nt 20103 molecular nutrition.pptx

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NT 20103 MOLECULAR

NUTRITION Group Assignment

THE CONTROVERSIAL PLACE OF

VITAMIN C IN CANCER TREATMENT

10/26/20131

NO NAME MATRIC NUMBER 1 CHANG YONG SIAN BN 11110032 2 KANG CHAI WEN BN 11110079 3 SIN WENG SAM BN 11110181

4 VOO JIA CHUN (LEADER) BN 11110216



Vitamin C related to scurvy (diet lacks in fresh

fruits& vegetables )

Active agent in fresh citrus fruit cures scurvy

known as a new glucose derivative (the enolic form of 3-oxo-L-gulofuranolactone)

10/26/20132

Antiscorbutic activity of this compound was

gave to a trivial name of ascorbic acid (AA)

Few years later:

chemical structure of ascorbic acid wasestablished in lab & known as Vitamin C



Ascorbic acid synthesis via hexuronic acid pathwayof the liver or the kidney.

Enzyme involved is called gulonolactone oxidase

• Up to 500mg, vitamin C is absorbed via asodium dependent active transport process.

• At Higher dose, diffusion occur.

Ascorbic acid in cells oxidized to

dehydroascorbic acid

Ascorbic acid then transported by sodium-

dependent transporters SVCT1 and SVCT2.

10/26/20133



2 facts explain Vitamin C as a powerful

water-soluble antioxidant

1st- ascorbate and ascorbyl radical have one-

electron state & exist at low one-electronreduction state.

2nd- ascorbate easily regenerated from DHA

& ascorbyl radical either enzymatically ornon-enzymatically

10/26/20134



Ascorbate may also is the lead for the pro-oxidanteffects through the reduction of transition metalions like iron and copper.

Ascorbate lower quinoid compounds that lead togeneration of a semiquinone radical which eventuallyreoxidized by molecular oxygen

Known biological activities

• Catalysis by donating electrons to metal ion

cofactors of hydroxylase enzymes.

• Helps in iron absorption by overcome the inhibitoryeffect of strong metal chelators.

10/26/20135



Vitamin C (Ascorbate) Reactive Oxygen Species (ROS)

Equilibrium between ROS formation andantioxidant defense mechanism is interrupted

Oxidative Stress

Injury to cellular componentse.g proteins, DNA, membrane lipids

Cell Death in Cancer Cell Lines



Allkylating Agents & Radioactive Isotopes

Kill cancer cells

Superoxide Dismutase (SOD)

Enzyme for elimination of superoxide radicals

Antioxidant in aerobic cells

Deficiency in SOD / Inhibition of Enzyme Activity

Accumulation of Superoxide Free Radicals

Cellular Injury & Cell Death



Site of Hydrogen Peroxide Production by Ascorbate Extracellular Fluids

Vitamin C acts as pro-drug to deliver hydrogen peroxide into tissues

Dehydroascorbic Acid Transported by Glucose Transporter

Accumulation of Vitamin C in Tumors

Cancer Cell High Endogenous levels of ROS

Destroyed by ROS-Promoting Agents



Influence on anticancer treatment

Studies showed that vitamin C have influence onactivity of radiotherapy and chemotherapy.

Eg: 5-fluorouracil

vitamin C can improve theeffectiveness of 5-fluorouracil chemotherapies.

NIH release a research showing definite indicationof vitamin C’s anti-cancer effect.

Ascorbate injected into vein or abdominal cavities of rodents with aggressive brain, ovarian, and pancreatictumors.

Reduced tumor size and growth by 41-53%.



10/26/201310

From the table, vitamin C

has reported to increase the

efficacy of several

chemotherapeutic drugs either invitro of in vivo. But some of the

activity of some agents seems to

decrease when ascorbic acid is

used simultaneously. This can be

the consequences of a directinactivation of the drug in vitro by

vitamin C. Importantly; the oral

supplementation of vitamin C

(together with antioxidants)

seems to have no influence onthe outcome of the patient who

undergoing chemotherapy.



Activation of the transcription factorhypoxia- inducible factor 1 (HIF-1).

Hydroxylation of proline residues inHIF-1 α by prolyl hydroxylases

important for the progression of tumour.

Modification in a vast range of cellularfunctions that allow cancer cells tonot only survive but to continue to

proliferate and metastasize.



Uncertainties and controversies

during the research•In vitro activity of prolyl hydroxylases is enhanced by the presence of ascorbate

that plays the role as cofactor by maintaining the iron centre of hydroxylase in a

reduced state.

•

Treatment of MDA468 breast carcinoma cells with 100 µM CoCl2, 100 µM DFO, orexposure to hypoxia (0.4% O2) induced high-level expression of HIF-1 α protein. In

the presence of 400 µM ascorbate, levels of HIF-1 α induced by DFO were reduced

3-fold, and HIF-1 α induction in response to CoCl2 was inhibited completely.

•Ascorbate had little or no effect on the level of HIF-1 α induced by severe hypoxia.

•Treatment of PC3 prostate carcinoma with ascorbate concentration ranging from

25 to 400 µM reduced HIF-1 α to undetectable levels under normoxic condition.

•Hypoxia-induced HIF-1 α was unaffected by even the highest dose of ascorbate.



Thank You!

10/26/201313

nt 20103 molecular nutrition.pptx

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