Interactions with Gamma-Linolenic Acid (GLA)

The activity of ceftazidime against Pseudomonas aeruginosa appears to be potentiated by fatty acids, including GLA (Giamarellos-Bourboulis et al. 1999). In vitro, GLA exerts bacteriostatic effects on Escherichia coli and, in combination with arachidonic acid, is bacteriocidal to P aeruginosa.

Cisplatin; Doxorubicin

In ovarian cancer cells, pre-incorporation of either gamma-linolenic acid (GLA) or eicosapentaenoic acid (EPA) increased sensitivity to doxorubicin and cisplatin; however, it was difficult to distinguish the cytotoxicity of the drug from the fatty acid (Plumb et al. 1993). The cytotoxicity of the fatty acids was additive with that of the drugs. Another study investigating the effectiveness of this combination therapy on human neuroblastoma cell lines found that addition of GLA to the growth medium reduced the cytotoxic effects of cisplatin and carboplatin (Ikushima et al. 1990).

Idarubicin; Mitoxantrone

Preclinical data suggest a possible enhancement of cellular uptake of idarubicin when cells are enriched with GLA (Davies et al. 1999). In multidrug resistant human breast cancer and bladder cancer cells, pre-incorporation of GLA at non-cytotoxic levels increased the cellular uptake of idarubicin. In addition, GLA changed the intracellular distribution of mitoxantrone.

Tamoxifen

GLA may interact with the estrogen receptor antagonist tamoxifen. In one short-term phase II clinical trial, high-dose GLA therapy (8 capsules/day po supplying 2.8 g GLA) potentiated the effects of tamoxifen (20 mg od) in 38 stage I-II breast cancer patients, 90% of whom were estrogen receptor-positive (Kenny et al. 2000). Patients given GLA exhibited a faster treatment response that was evident by 6 weeks.

Vincristine; Vinblastine

In human neuroblastoma cell lines, addition of GLA to the growth medium enhanced the cytotoxic effects of the vinca alkaloids, vincristine, vinblastine, and vindesine (Ikushima et al. 1990). In both vincristine-sensitive and -resistant human cervical cancer cells, GLA was cytotoxic (Madhavi and Das 1994).

References

Davies CL, Loizidou M, Cooper AJ, et al. Effect of gamma-linolenic acid on cellular uptake of structurally related anthracyclines in human drug sensitive and multidrug resistant bladder and breast cancer cell lines. Eur J Cancer. 1999;35:1534-1540.

Giamarellos-Bourboulis EJ, Grecka P, Dionyssiou-Asteriou A, et al. In vitro interactions of gamma-linolenic acid and arachidonic acid with ceftazidime on multiresistant Pseudomonas aeruginosa. Lipids. 1999;34:S151-152.

Ikushima S, Fujiwara F, Todo S, Imashuku S. Gamma linolenic acid alters the cytotoxic activity of anticancer drugs on cultured human neuroblastoma cells. Anticancer Res. 1990;10:1055-1059.

Kenny FS, Pinder SE, Ellis IO et al. Gamma linolenic acid with tamoxifen as primary therapy tn breast cancer. Int J Cancer. 2000;85:643-648.

Madhavi N, Das UN. Effect of n-6 and n-3 fatty acids on the survival of vincristine sensitive and resistant human cervical carcinoma cells in vitro. Cancer Lett. 1994;84:31-41.

Plumb JA, Luo W, Kerr DJ. Effect of polyunsaturated fatty acids on the drug sensitivity of human tumour cell lines resistant to either cisplatin or doxorubicin. Br J Cancer. 1993;67:728-733.

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