New
Findings on the Role of Glutathione in Cancer
Copyright
© 2004 Priya Shah
Cancer cells
and normal cells are known to respond differently to nutrients
and drugs that affect glutathione status.
Numerous studies
have shown that tumor cells have elevated levels of glutathione
levels, which confers resistance to chemotherapy drugs.
One of the
challenges of cancer therapy is how to deplete tumor cells of
glutathione, so as to make them more vulnerable to the effects
of chemotherapy drugs, while at the same time allowing normal
cells to remain relatively unaffected by chemotherapeutic drugs.
A number of
new findings have emerged that take into consideration the role
of glutathione in pathways that promote programmed cell death
(apoptosis) in cancer cells.
A German study
has reported that glutathione (GSH) plays a critical role in cellular
mechanisms that result in cell death. The study found that cancer
cells resistant to apoptosis had higher intracellular GSH levels.
Depletion
of glutathione in these tumor cells made them more vulnerable
to the effects of anticancer drugs or the gene that promotes apoptosis
(CD95 or APO-1/Fas). The researchers concluded that apoptosis
resistance in tumor cells depends, at least in part, on intracellular
GSH levels. (1)
In another
study conducted in Spain, researchers found that lowering GSH
concentration may be convenient not only for the efficiency of
chemotherapy, but also to induce a rather fast and direct apoptosis
mechanism in tumor cells. (2)
Based on that
premise that the glutathione-S-transferase enzyme is expressed
at high levels in many tumors, researchers at the Fox Chase Cancer
Center in Pennsylvania, went on to design a novel prodrug (PABA/NO).
The glutathione-s-transferase
in tumor cells converts PABA/NO to lethal nitric oxide, resulting
in death of the tumor cell. The prodrug was shown to have antitumor
effects in an animal model for human ovarian cancer. (3)
In the fourth
study, Polish researchers found that ingesting a selenium supplement
is beneficial, as a supportive element in chemotherapy. (4)
Selenium is
a co-factor of the enzyme glutathione peroxidase [GSH-P(x)] and
was found to significantly increase the activity of GSH-P(x) in
patients reciving the supplement.
A previous
clinical study by the same researchers recommended the administration
of selenium in patients with ovarian cancer undergoing multi-drug
chemotherapy. (5)
Another interesting
study by researchers in Texas showed that your chances of surviving
a type of brain cancer, called primary malignant glioma, could
depend on the type of glutathione-s-transferase (GST) gene you
were born with.
Having a combination
of a two specific variants of GST (germ-line GSTP1*A/*A and GSTM1
null genotype) confers a survival advantage in some types of brain
cancers, but also comes with an increased risk of adverse events
related to chemotherapy. (6)
There is compelling
evidence to suggest a crucial role for glutathione and substances
that target glutathione metabolism in the prevention and treatment
of cancer.
Undenatured
whey protein is one of the natural foods known to selectively
deplete cancer cells of their glutathione, thus making them more
susceptible to such cancer treatments as radiation and chemotherapy.
For a complete
report on the research on undenatured whey protein and cancer
see the report Glutathione
(GSH) and Whey Protein in Cancer.
Disclaimer:
The information here is not provided by medical professionals
and is not intended as a substitute for medical advice. Please
consult your physician before beginning any course of treatment.
References:
1. A
critical role of glutathione in determining apoptosis sensitivity
and resistance in leukemia cells
Friesen C et al. [Cell Death and Differentiation advance
online publication, 23 April 2004; doi:10.1038/sj.cdd.4401431]
2. Role
of glutathione in the induction of apoptosis and c-fos and c-jun
mRNAs by oxidative stress in tumor cells
Tormos C et al. [Cancer Lett. 2004 May 10;208(1):103-13.]
3. Tumor
cell responses to a novel glutathione s-transferase-activated
nitric oxide-releasing prodrug
Findlay VJ et al. [Mol Pharmacol. 2004 May;65(5):1070-9.]
4. Selenium
as an element in the treatment of ovarian cancer in women receiving
chemotherapy
Sieja K et al. [Gynecol Oncol. 2004 May;93(2):320-327.]
5. Selenium
(Se) deficiency in women with ovarian cancer undergoing chemotherapy
and the influence of supplementation with this micro-element on
biochemical parameters
Sieja K. [Pharmazie. 1998 Jul;53(7):473-6.]
6. Glutathione
S-transferase polymorphisms and survival in primary malignant
glioma
Okcu MF et. al. [Clin Cancer Res. 2004 Apr 15;10(8):2618-25.]
This article
was first published in the April 2004 issue of The
Glutathione Report, a newsletter featuring regular updates
on the health benefits of glutathione. Get a Free
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