Effect of dietary GLA+/?tamoxifen on the growth, ER expression and fatty acid profile of ER positive human breast cancer xenografts

ω‐6 Polyunsaturated fatty acid γ‐linolenic acid (18:3n‐6) is a selective estrogen‐response modulator in human breast cancer cells: γ‐Linolenic acid antagonizes estrogen receptor‐dependent transcriptional activity, transcriptionally represses estrogen receptor expression and synergistically enhances tamoxifen and ICI 182,780 (Faslodex) efficacy in human breast cancer cells

“…[11][12][13] Our own group has shown that GLA is able to enhance synergistically the in vitro anticancer actions of microtubule-interfering agents such as paclitaxel (Taxol) and vinorelbine (Navelbine). 14,15 Our current results extend earlier observations made by Kenny et al,5,7 supporting the notion that -6 PUFA GLA functions as a novel selective modulator of ER (SERM) in hormone-responsive human breast cancer cells. Remarkably, it appears that the antiestrogenic activity of GLA involves a novel molecular mechanism via transcriptional repression of ER gene.…”

“…5 In addition, GLA treatment also resulted in a highly significant reduction of ER expression in xenografts models of ER-positive breast cancer, raising the possibility of an additive or synergistic growth-inhibitory action of GLA and TAM via enhanced downregulation of the ER machinery. 7 However, the ultimate mechanisms responsible for GLA-induced modulation of ER signaling and better clinical response to antiestrogens did remain to be elucidated.…”

“…These observations are consistent with both the encouraging results from a phase 2 study employing high-dose oral GLA in combination with TAM in endocrine-sensitive breast cancer 5 and the sensitizing effects of dietary GLA on TAM-induced growth inhibition of ER-positive human breast cancer xenografts. 7 To investigate how GLA interrupted E 2 -dependent mitogenic ER signaling, we finally evaluated the effects of GLA in the levels of cyclin-dependent kinases inhibitors (CDK i s) p21 WAF1/CIP1 and p27 Kip1 , both playing essential roles in hormone-dependent tumor cell growth. In fact, p21 WAF1/CIP1 and p27…”

Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling

“…g-linolenic acid has several properties that might make it antitumorigenic. Kenny et al (2001) have shown that g-linolenic acid reduces the growth of MCF-7 xenografts, reduces ER levels in these cells, and potentiates TAM's ability to inhibit cell growth. However, the precise mechanism of action of g-linolenic acid remains to be determined.…”

Effect of gamma linolenic acid pretreatment on diabetic neuropathy in rats

“…GLA has been shown to exert beneficial effects in rheumatoid arthritis, 12 atopic eczema, 13 acute respiratory distress syndrome, 14 Asthma, 15 ulcerative colitis, 16 cancer, 17 and osteoporosis. 18 Investigations have demonstrated that GLA treatment improved autoimmune diseases 12 and diabetic neuropathy via an anti inflammatory mechanism.…”