γ

-Linolenic Acid: Purification and Functionality

65

of specific PUFA substrates may be due to reduced formation or uptake of PUFA
by tumor cells. Several investigators have showed that tumor cells are deficient in
PUFAs and contain higher amounts of oleic acid and decreased amounts of AA and
C22 PUFAs [162]. Since the longer chain PUFAs stimulate higher rates of lipid oxidation
than C18 PUFAs, this may be one of the rate-limiting factors in lipid peroxidation
in tumor cells. Decomposed lipid peroxidation products (e.g., malonaldehyde,
4-hydroxynonadienal, 4-hydroxyhexenal) generated from PUFAs may have a regu-
lating effect on DNA duplication enzymes, and thus function in regulating cell
proliferation and uncontrolled tumor cell growth [159]. The reviews provided by
Das [142] and De Vries and Van Noorden [159] extensively discussed how EFAs,
including GLA, affect tumor cells via the lipid peroxidation pathway.

In the studies on growth and metastatis of rodent mammary tumor cells, atten-

uated levels of PGE

1

 were found in opposition to PGE

2

 in nonmetastatic cells

[163–165]. AA-derived eicosanoids play an important role in down regulating growth
and metastasis of tumor cells.

In mixed culture cells, GLA showed a more selective tumoricidal action than did

AA or EPA [139] and in vivo studies showed antitumor [166] and antiangiogenic [167]
activities and may increase the sensitivity of tumor cells to radiation and chemother-
apeutic agents [168,169]. Das and co-workers [170] and Bakashi and group [171]
described the use of GLA as a therapy for human gliomas, which can occur anywhere
in the brain but usually affect the cerebral hemisphere. They have treated patients with
grade-4 gliomas with 1 mg GLA for 7 d by intratumoral injection. It was concluded
from this study that GLA is capable of enhancing the sensitivity of tumor cells to
conventional anticancer and radiation treatments as found in studies of breast cancer
[172,173] and also has the beneficial property of the lack of side effects.

Studies on GLA related to cancer therapy propose that GLA has a value as a

new cancer therapeutic agent having selective antitumor properties with negligible
systemic toxicity. The proposed mechanisms of activities include modulation of
steroid hormone receptors (e.g., estrogen receptors in breast cancer). The clinical
study carried out by Kenny et al. [172] concludes that GLA is a useful adjunct to
primary tamoxifen treatment in endocrine-sensitive breast cancer. GLA may affect
on estrogen receptor function and exert an additive or synergistic action with tamoxifen
via enhanced down regulation of estrogen receptor-stimulated growth.

3.4.4 D

IABETES

 

AND

 R

ELATED

 C

ONDITIONS

It is found that desaturation and elongation of LA are decreased in subjects with
type 1 diabetes (insulin-dependent, diabetes mellitus) [174]. Decreased levels of
DGLA and AA in serum lipids in association with increased plasma levels of PGE

2

and PGF

2

α

 have also been observed. In children with deficient levels of insulin and

high levels of blood sugar supply, formation of DGLA from LA is lowered and
decreased formation of PGE

1

 has been observed [175]. Under conditions of diabetes

mellitus, this restricted conversion of dietary LA to GLA has been attributed to the
reduced 

∆

6-desaturase activity [176,177].

Platelet abnormalities are linked with vascular disease and diabetes has a high

incidence of vascular complications. Studies on the fatty acid composition of platelet

2162_C003.fm  Page 65  Monday, June 20, 2005  12:27 PM

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