Related Experiment Video
Updated: Aug 14, 2026
A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions
Published on: May 27, 2021
Anacardic Acid, Salicylic Acid, and Oleic Acid Differentially Alter Cellular Bioenergetic Function in Breast Cancer
Brandie N Radde1, Negin Alizadeh-Rad1, Stephanie M Price1
1Department of Biochemistry & Molecular Genetics, University of Louisville School of Medicine, University of Louisville, Louisville, Kentucky 40292.
Abstract:
Anacardic acid is a dietary and medicinal phytochemical that inhibits breast cancer cell proliferation and uncouples oxidative phosphorylation (OXPHOS) in isolated rat liver mitochondria. Since mitochondrial-targeted anticancer therapy (mitocans) may be useful in breast cancer, we examined the effect of anacardic acid on cellular bioenergetics and OXPHOS pathway proteins in breast cancer cells modeling progression to endocrine-independence: MCF-7 estrogen receptor α (ERα)+ endocrine-sensitive; LCC9 and LY2 ERα+, endocrine-resistant, and MDA-MB-231 triple negative breast cancer (TNBC) cells. At concentrations similar to cell proliferation IC50 s, anacardic acid reduced ATP-linked oxygen consumption rate (OCR), mitochondrial reserve capacity, and coupling efficiency while increasing proton leak, reflecting mitochondrial toxicity which was greater in MCF-7 compared to endocrine-resistant and TNBC cells. These results suggest tolerance in endocrine-resistant and TNBC cells to mitochondrial stress induced by anacardic acid. Since anacardic acid is an alkylated 2-hydroxybenzoic acid, the effects of salicylic acid (SA, 2-hydroxybenzoic acid moiety) and oleic acid (OA, monounsaturated alkyl moiety) were tested. SA inhibited whereas OA stimulated cell viability. In contrast to stimulation of basal OCR by anacardic acid (uncoupling effect), neither SA nor OA altered basal OCR- except OA inhibited basal and ATP-linked OCR, and increased ECAR, in MDA-MB-231 cells. Changes in OXPHOS proteins correlated with changes in OCR. Overall, neither the 2-hydroxybenzoic acid moiety nor the monounsaturated alky moiety of anacardic acid is solely responsible for the observed mitochondria-targeted anticancer activity in breast cancer cells and hence both moieties are required in the same molecule for the observed effects. J. Cell. Biochem. 117: 2521-2532, 2016. © 2016 Wiley Periodicals, Inc.
Insights
Anacardic acid shows anticancer effects by disrupting mitochondrial energy production in breast cancer cells. Its full structure, not just parts, is crucial for this mitochondria-targeted activity.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Anacardic acid is a phytochemical with anticancer properties.
- Mitochondrial-targeted anticancer therapy (mitocans) is a potential strategy for breast cancer.
- Breast cancer exhibits diverse subtypes with varying endocrine sensitivity.
Purpose of the Study:
- To investigate the effects of anacardic acid on cellular bioenergetics and oxidative phosphorylation (OXPHOS) in different breast cancer models.
- To determine the role of anacardic acid's chemical moieties in its anticancer activity.
- To assess the differential sensitivity of endocrine-sensitive, endocrine-resistant, and triple-negative breast cancer cells to anacardic acid.
Main Methods:
- Cellular bioenergetics assays measuring oxygen consumption rate (OCR) and extracellular acidification rate (ECAR).
- Analysis of oxidative phosphorylation (OXPHOS) pathway proteins.
- Treatment of breast cancer cell lines (MCF-7, LCC9, LY2, MDA-MB-231) with anacardic acid, salicylic acid, and oleic acid.
Main Results:
- Anacardic acid reduced ATP-linked OCR, mitochondrial reserve capacity, and coupling efficiency, increasing proton leak, indicating mitochondrial toxicity.
- Mitochondrial toxicity was greater in estrogen receptor α (ERα)+ endocrine-sensitive MCF-7 cells compared to endocrine-resistant and triple-negative breast cancer (TNBC) cells.
- Neither salicylic acid nor oleic acid alone replicated the full mitochondria-targeted anticancer effects of anacardic acid, suggesting both moieties are required.
Conclusions:
- Anacardic acid exhibits mitochondria-targeted anticancer activity by impairing cellular bioenergetics and OXPHOS.
- Breast cancer cells display varying tolerance to anacardic acid-induced mitochondrial stress.
- The combined 2-hydroxybenzoic acid and monounsaturated alkyl moieties within anacardic acid are essential for its observed mitochondria-targeted anticancer efficacy.
