Fatty acid synthase regulates the chemosensitivity of breast cancer cells to cisplatin-induced apoptosis

Al-Bahlani, Shadia; Al-Lawati, Hanaa; Al-Adawi, Moza; Al-Abri, Nadia; Al-Dhahli, Buthaina; Al-Adawi, Kawther

doi:10.1007/s10495-017-1366-2

Cited by 58 publications

(42 citation statements)

References 36 publications

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“…Fatty acids are essential components of biofilm lipids, signaling molecules and constituents of energy metabolism pathways (30)(31)(32). Among them, palmitic acid serves a prominent role in the formation of long-chain fatty acids containing 16 carbon atoms (C16:0), and studies have reported excessive accumulation of palmitic acid in breast cancer cells (33)(34)(35). ELOVL6 is a key enzyme in intracellular lipid metabolism, and has previously been associated with metabolism in fatty liver and diabetes (36).…”

Section: Discussionmentioning

confidence: 99%

Decreased expression levels of ELOVL6 indicate poor prognosis in hepatocellular carcinoma

Li¹,

Wang²,

Tang³

et al. 2019

Oncol Lett

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The present study aimed to investigate the expression of elongation of very long-chain fatty acids family member 6 (ELOVL6) in hepatocellular carcinoma (HCC) tissues, and to determine its role in the development of HCC. A total of 377 HCC specimens were collected for tissue microarray and immunohistochemistry analyses. The ELOVL6 IHC score for HCC tissues was 0.97±0.71, which was significantly lower than that of the matched adjacent normal tissues (1.32±0.68; P<0.001). Patients with low levels of ELOVL6 expression were older (P=0.014) and possessed larger sized tumors (P=0.039) than patients with high expression levels. Additionally, Kaplan-Meier analysis revealed that patients with low ELOVL6 expression levels also had significantly poorer overall (P<0.001) and disease-free (P=0.029) survival times, and a greater probability of recurrence. The tumor size, tumor-node-metastasis (TNM) stage, vascular invasion and ELOVL6 expression were all shown to be prognostic variables for overall survival in patients with HCC. Multivariate analysis revealed that vascular invasion (P<0.001), TNM stage (P<0.001) and ELOVL6 expression (P=0.001) were independent prognostic variables for overall survival. In addition, vascular invasion (P=0.032) and ELOVL6 expression (P=0.041) were independent risk factors for disease-free survival, and vascular invasion (P=0.019) and ELOVL6 expression (P=0.045) were independent risk factors associated with HCC recurrence. The present study revealed that in patients with HCC, ELOVL6 expression level was reduced in HCC tissues, and that higher ELOVL6 expression levels correlated with longer survival times. This indicates that ELOVL6 may serves as an independent marker of poor patient outcome.

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Section: Discussionmentioning

confidence: 99%

Decreased expression levels of ELOVL6 indicate poor prognosis in hepatocellular carcinoma

Li¹,

Wang²,

Tang³

et al. 2019

Oncol Lett

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“…This illustrates that FASN plays an oncogenic role in cisplatin-induced apoptosis of TNBC cells. FASN suppression in TNBC can therefore enhance cisplatin-induced apoptosis to overcome chemoresistance (119). Intensified FAO is also a characteristic of chemoresistant TNBC tumor cells.…”

Section: Impact Of Metabolic Reprogramming On Tnbc Chemoresistancementioning

confidence: 99%

Metabolic Reprogramming in Triple-Negative Breast Cancer

et al. 2020

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Metabolic reprogramming is an emerging hallmark of cancer cells, in which cancer cells exhibit distinct metabolic phenotypes to fuel their proliferation and progression. The significant advancements made in the area of metabolic reprogramming make possible new strategies for overcoming malignant cancer, including triple-negative breast cancer. Triple-negative breast cancer (TNBC) is associated with high histologic grade, aggressive phenotype, and poor prognosis. Even though triple-negative breast cancer patients benefit from standard chemotherapy, they still face high recurrence rates and are more likely to develop resistance to chemotherapeutic drugs. Therefore, there is an urgent need to explore vulnerabilities of triple-negative breast cancer and develop novel therapeutic drugs to improve clinical outcomes for triple-negative breast cancer patients. Metabolic reprogramming may provide promising therapeutic targets for the treatment of triple-negative breast cancer. In this paper, we primarily discuss how triple-negative breast cancer cells reprogram their metabolic phenotype and that of stromal cells in the microenvironment to survive under nutrient-poor conditions. Considering that metastasis and chemoresistance are the main contributors to mortality in triple-negative breast cancer patients, we also focus on the role of metabolic adaption in mediating metastasis and chemoresistance of triple-negative breast cancer tumors.

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“…However, multiple mechanisms of cisplatin-resistance have been identified in TNBC cells ( 118 ). Despite the potential deleterious effects of oleic acid on TNBC cells, one study demonstrated a potential synergistic relationship between oleate and Cisplatin on inducing apoptosis in MDA-MB-231 cells ( 68 ). Treatment with oleate (50 μM) increased the number of cells undergoing apoptosis when used in combination with Cisplatin compared to cells treated with Cisplatin alone, which was attributed to oleic acid-dependent downregulation of fatty acid synthase (FASN).…”

Section: Olive Oil and Tnbc: Reviewmentioning

confidence: 99%

Do Olive and Fish Oils of the Mediterranean Diet Have a Role in Triple Negative Breast Cancer Prevention and Therapy? An Exploration of Evidence in Cells and Animal Models

et al. 2020

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Breast cancer is the most common malignancy and cause of cancer-related mortality among women worldwide. Triple negative breast cancers (TNBC) are the most aggressive and lethal of the breast cancer molecular subtypes, due in part to a poor understanding of TNBC etiology and lack of targeted therapeutics. Despite advances in the clinical management of TNBC, optimal treatment regimens remain elusive. Thus, identifying interventional approaches that suppress the initiation and progression of TNBC, while minimizing side effects, would be of great interest. Studies have documented an inverse relationship between the incidence of hormone receptor negative breast cancer and adherence to a Mediterranean Diet, particularly higher consumption of fish and olive oil. Here, we performed a review of studies over the last 5 years investigating the effects of fish oil, olive oil and their components in model systems of TNBC. We included studies that focused on the fish oil ω-3 essential fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in addition to olive oil polyphenolic compounds and oleic acid. Both beneficial and deleterious effects on TNBC model systems are reviewed and we highlight how multiple components of these Mediterranean Diet oils target signaling pathways known to be aberrant in TNBC including PI3K/Akt/mTOR, NF-κB/COX2 and Wnt/β-catenin.

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Fatty acid synthase regulates the chemosensitivity of breast cancer cells to cisplatin-induced apoptosis

Cited by 58 publications

References 36 publications

Decreased expression levels of ELOVL6 indicate poor prognosis in hepatocellular carcinoma

Decreased expression levels of ELOVL6 indicate poor prognosis in hepatocellular carcinoma

Metabolic Reprogramming in Triple-Negative Breast Cancer

Do Olive and Fish Oils of the Mediterranean Diet Have a Role in Triple Negative Breast Cancer Prevention and Therapy? An Exploration of Evidence in Cells and Animal Models

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