Arachidonic acid induces ER stress and apoptosis in HT-29 human colon cancer cells

Abstract

Polyunsaturated fatty acids (PUFAs) have important functions in biological systems. The beneficial effects of dietary PUFAs against inflammatory diseases, cardiovascular diseases, and metabolic disorders have been shown. Studies using cancer cells have presented the anti-tumorigenic effects of docosahexaenoic acid (DHA), an n-3 PUFA, while arachidonic acid (AA), an n-6 PUFA, has been shown to elicit both pro-and anti-tumorigenic effects. In the current study, the antitumorigenic effects of AA were evaluated in HT-29 human colon cancer cells. Upon adding AA in the media, more than 90% of HT-29 cells died, while the MCF7 cells showed good proliferation. AA inhibited the expression of SREBP-1 and its target genes that encode enzymes involved in fatty acid synthesis. As HT-29 cells contained lower basal levels of fatty acid synthase, a target gene of SREBP-1, than that in MCF7 cells, the inhibitory effects of AA on the fatty acid synthase levels in HT-29 cells were much stronger than those in MCF-7 cells. When oleic acid (OA), a monounsaturated fatty acid that can be synthesized endogenously, was added along with AA, the HT-29 cells were able to proliferate. These results suggested that HT-29 cells could not synthesize enough fatty acids for cell division in the presence of AA because of the suppression of lipogenesis. HT-29 cells may incorporate more AA into their membrane phospholipids to proliferate, which resulted in ER stress, thereby inducing apoptosis. AA could be used as an antitumorigenic agent against cancer cells in which the basal fatty acid synthase levels are low.

Kazinol C from Broussonetia kazinoki stimulates autophagy via endoplasmic reticulum stress-mediated signaling

“…It will be interesting to investigate in details the proteins that Kazinol C and DFS target to induce these cellular events. ER stress inducers, such as tunicamycin and arachidonic acid, induce apoptosis, as Kazinol C does in cancer cells (Bae et al 2020 ; Kong et al 2020 ). Therefore, blocking autophagy along with the induction of ER stress would be a more effective way to induce cancer cell death.…”

Relationship of endoplasmic reticulum stress with the etiopathogenesis of chronic tonsillitis and tonsillar hypertrophy in pediatric patients: a prospective, parallel-group study

“…In a study evaluating the antitumorigenic effects of Arachidonic acid (AA) in HT-29 human colon cancer cells, the resulting ER stress in HT-29 cells treated with AA was demonstrated by an increase in the level of the processed form of XBP1 and phosphorylated eIF2α [21]. The resultant ER stress and induced apoptosis were thought to result from the provision of more AA to membrane lipids and altered membrane properties of the ER.…”

A Metabolomics Investigation of the Metabolic Changes of Raji B Lymphoma Cells Undergoing Apoptosis Induced by Zinc Ions

“…Y79 cell exposure to AA revealed a significant increase in lipid peroxidation end products and a sharp drop in mitochondrial membrane potential, resulting in apoptosis [29]. AA inhibits SREBP−1 and blocks the endogenous synthesis of fatty acids, leading to endoplasmic reticulum (ER) stress and apoptosis in HT−29 colon cancer cells [30]. Moreover, treatment with apoptotic concentrations of AA involves changes in oxidative stress and eicosanoid biosynthesis in leucocytes [27].…”