Alpha-linolenic acid stabilizes HIF-1 α and downregulates FASN to promote mitochondrial apoptosis for mammary gland chemoprevention

Abstract

Alpha linolenic acid is an essential polyunsaturated fatty acid and is reported to have the anti-cancer potential with no defined hypothesis or mechanism/s. Henceforth present study was in-quested to validate the effect of alpha linolenic acid on mitochondrial apoptosis, hypoxic microenvironment and de novo fatty acid synthesis using in-vitro and in-vivo studies. The IC50 value of alpha linolenic acid was recorded to be 17.55μM against ER+MCF-7 cells. Treatment with alpha linolenic acid was evident for the presence of early and late apoptotic signals along with mitochondrial depolarization, when studied through acridine orange/ethidium bromide and JC-1 staining. Alpha linolenic acid arrested the cell cycle in G2/M phase. Subsequently, the in-vivo efficacy was examined against 7, 12-dimethylbenz anthracene induced carcinogenesis. Treatment with alpha linolenic acid demarcated significant effect upon the cellular proliferation as evidenced through decreased in alveolar bud count, restoration of the histopathological architecture and loss of tumor micro vessels. Alpha linolenic acid restored the metabolic changes to normal when scrutinized through 1H NMR studies. The immunoblotting and qRT-PCR studies revealed participation of mitochondrial mediated death apoptosis pathway and curtailment of hypoxic microenvironment after treatment with alpha linolenic acid. With all above, it was concluded that alpha linolenic acid mediates mitochondrial apoptosis, curtails hypoxic microenvironment along with inhibition of de novo fatty acid synthesis to impart anticancer effects.

Intestinal microbiome and related diseases: A recent updated review

“…The blood plasma of the patients with autism showed the increase in most of saturated fatty acids, except propionic acid and the decrease in most of unsaturated fatty acids that can be related to the several processes including oxidative stress to disorders in mitochondria and leads to the metabolic resulted from the changes in the patients with autism. This was recently shown by Subhadeep et al (2017), in a research on the comparison of the relative concentration of necessary fatty acids (linoleic and linolinic alpha), the long unsaturated fatty acids and phospholipids in the plasma of the patients with autism in Saudi Arabia with the control group of the same age. They reported the remarkable modulation of fatty acid metabolism that was evaluated by the change of the ratio among necessary fatty acids, long unsaturated fatty acids and omega 3, omega 6 fatty acids and the decrease of the circulation level of phospholipids.…”

Activation of prolyl hydroxylase‐2 for stabilization of mitochondrial stress along with simultaneous downregulation of HIF‐1α/FASN in ER + breast cancer subtype

“…35 All the tissue samples were dried by the critical point method. 35 All the tissue samples were dried by the critical point method.…”

“…35 The sequence of forward and reverse primers is elaborated in Table S1. 35 The sequence of forward and reverse primers is elaborated in Table S1.…”

“…The surface architecture of the tissue was studied using the method elaborated by us previously. 35 All the tissue samples were dried by the critical point method. The tissue sections were visualized, and images were captured through scanning electron microscopy (SEM) (JEOL JSM-6490LV).…”

“…The real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) study of various genes was performed according to the method elaborated elsewhere. 35 The sequence of forward and reverse primers is elaborated in Table S1.…”