I read with interest the study by Siddiqui et al.In a series of studies, previously I reported that long-chain polyunsaturated fatty acids (LCPUFAs) have selective tumoricidal action on a variety of tumor cells with little or no effects on normal cells both in vitro and in vivo (1-5). Our studies showed that human breast cancer cells ZR-75-1 are killed by LCPUFAs. Of all the fatty acids tested gamma-linolenic acid (GLA) was found to be the most effective compared to EPA and DHA. Subsequent studies revealed that LCPUFAs are able to enhance free radical generation and lipid roxidation process in tumor cells but not in normal cells and that this could be one of the main, if not the sole, mechanism of their tumoricidal action. It was also observed that anti-oxidants such as BHA, BHT and vitamin E interfere with the tumoricidal actions of LCPUFAs. In an extension of these studies, it was observed that intra-tumoral injection of GLA could regress human glioma and that modified GLA has anti-vascular and anti-angiogenic actions as well (6, 7). Based on these studies, I believe that GLA and other LCPUFAs could be exploited as potential anti-cancer agents. In this context, it is interesting to note that patients with breast cancer when given GLA showed decrease in estrogen receptor number in the tumor biopsies and had less progression of the disease.
In the light of these studies and the results reported by Siddiqui et al, it will be interesting to do further studies on the relationship between LCPUFAs and cancer.
References:
1.Begin ME, Das UN, Ells G, et al. Selective killing of tumor cells by polyunsaturated fatty acids. Prostaglandins Leukotrienes Med. 19 : 177, 1985.
2. Das UN. Tumoricidal action of cis-unsaturated fatty acids and its relationship to free radicals and lipid peroxidation. Cancer Lett. 56 : 235-243, 1991.
3. Das UN, et al. Uptake and distribution of cis-unsaturated fatty acids and their effect
on free radical generation in normal and tumor cells in vitro. Free Rad Biol Med 3 : 9, 1987.
4. Das UN, et al. Polyunsaturated fatty acids augment free radical generation in tumor-
cells in vitro. Biochem Biophys Res Commun. 145 : 15, 1987.
5.Madhavi N and 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. 84 : 31-41, 1994.
6. Das UN. From bench to the clinic: γ-linolenic acid therapy of human gliomas. Prostaglandins Leukot Essen Fatty Acids 2004; 70: 419-426.
7. Das UN. Occlusion of infusion vessels on gamma-linolenic acid infusion. Prostaglandins
Leukotr Essen Fatty Acids 70; 23-32, 2004.
Competing interests
I am involved in the development of LCPUFAs-based drugs for various clinical conditions.
Long-chain polyunsaturated fatty acids and cancer
13 June 2005
I read with interest the study by Siddiqui et al.In a series of studies, previously I reported that long-chain polyunsaturated fatty acids (LCPUFAs) have selective tumoricidal action on a variety of tumor cells with little or no effects on normal cells both in vitro and in vivo (1-5). Our studies showed that human breast cancer cells ZR-75-1 are killed by LCPUFAs. Of all the fatty acids tested gamma-linolenic acid (GLA) was found to be the most effective compared to EPA and DHA. Subsequent studies revealed that LCPUFAs are able to enhance free radical generation and lipid roxidation process in tumor cells but not in normal cells and that this could be one of the main, if not the sole, mechanism of their tumoricidal action. It was also observed that anti-oxidants such as BHA, BHT and vitamin E interfere with the tumoricidal actions of LCPUFAs. In an extension of these studies, it was observed that intra-tumoral injection of GLA could regress human glioma and that modified GLA has anti-vascular and anti-angiogenic actions as well (6, 7). Based on these studies, I believe that GLA and other LCPUFAs could be exploited as potential anti-cancer agents. In this context, it is interesting to note that patients with breast cancer when given GLA showed decrease in estrogen receptor number in the tumor biopsies and had less progression of the disease.
In the light of these studies and the results reported by Siddiqui et al, it will be interesting to do further studies on the relationship between LCPUFAs and cancer.
References:
1.Begin ME, Das UN, Ells G, et al. Selective killing of tumor cells by polyunsaturated fatty acids. Prostaglandins Leukotrienes Med. 19 : 177, 1985.
2. Das UN. Tumoricidal action of cis-unsaturated fatty acids and its relationship to free radicals and lipid peroxidation. Cancer Lett. 56 : 235-243, 1991.
3. Das UN, et al. Uptake and distribution of cis-unsaturated fatty acids and their effect
on free radical generation in normal and tumor cells in vitro. Free Rad Biol Med 3 : 9, 1987.
4. Das UN, et al. Polyunsaturated fatty acids augment free radical generation in tumor-
cells in vitro. Biochem Biophys Res Commun. 145 : 15, 1987.
5.Madhavi N and 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. 84 : 31-41, 1994.
6. Das UN. From bench to the clinic: γ-linolenic acid therapy of human gliomas. Prostaglandins Leukot Essen Fatty Acids 2004; 70: 419-426.
7. Das UN. Occlusion of infusion vessels on gamma-linolenic acid infusion. Prostaglandins
Leukotr Essen Fatty Acids 70; 23-32, 2004.
Competing interests
I am involved in the development of LCPUFAs-based drugs for various clinical conditions.