Fatty acid oxidation protects cancer cells from apoptosis by increasing mitochondrial membrane lipids

Li, Yijia; Fahrmann, Johannes F.; Aftabizadeh, Maryam; Zhao, Qianqian; Tripathi, Satyendra Chandra; Zhang, Chunyan; Yuan, Yuan; Ann, David K.; Hanash, Samir M.; Yu, Hua

doi:10.1016/j.celrep.2022.110870

Cited by 44 publications

(35 citation statements)

References 72 publications

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“…In addition, it was found that SGI could significantly regulate the metabolism of arachidonic acid, sphingomyelin (SM), lysophosphatidylinositol (LysoPI), and lysophosphatidylethanolamine (LysoPE), which are closely related to the integrity of mitochondrial membranes and mitochondrial dynamics and are also closely associated with cell inflammation and apoptosis [50][51][52][53]. The results suggest that SGI critically contributed to the cardioprotective effect of DCM treatment partly via anti-inflammation and anti-apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Multiple mitochondria-targeted components screened from Sini decoction improved cardiac energetics and mitochondrial dysfunction to attenuate doxorubicin-induced cardiomyopathy

Ding¹,

Zhang²,

Pan³

et al. 2023

Theranostics

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Rationale: Sini decoction (SND) is an efficient formula against DOX-induced cardiomyopathy (DCM), but the active ingredient combination (AIC) and mechanisms of SND remain unclear. Therefore, the present study aimed to identify the AIC and elucidate the underlying mechanism of AIC on DCM. Methods: The AIC were screened by a novel comprehensive two-dimensional cardiac mitochondrial membrane chromatography (CMMC)-TOFMS analysis system and further validated by cell viability, reactive oxygen species (ROS) generation, ATP level, and mitochondrial membrane potential in DOX-induced H9c2 cell injury model. Then, an integrated model of cardiac mitochondrial metabolomics and proteomics were applied to clarify the underlying mechanism in vitro. Results: The CMMC column lifespan was significantly improved to more than 10 days. Songorine (S), neoline, talatizamine, 8-gingerol (G) and isoliquiritigenin (I), exhibiting stronger retention on the first-dimension CMMC column, were screened to have protective effects against DOX cardiotoxicity in the H9c2 cell model. S, G and I were selected as an AIC from SND according to the bioactivity evaluation and the compatibility theory of SND. The combined in vitro use of S, G and I produced more profound therapeutic effects than any component used individually on increasing ATP levels and mitochondrial membrane potential and suppressing intracellular ROS production. Moreover, SGI attenuated DCM might via regulating mitochondrial energy metabolism and mitochondrial dysfunction. Conclusions: The provided scientific evidence to support that SGI combination from SND could be used as a prebiotic agent for DCM. Importantly, the proposed two-dimensional CMMC-TOFMS analytical system provides a high-throughput screening strategy for mitochondria-targeted compounds from natural products, which could be applied to other subcellular organelle models for drug discovery.

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Section: Discussionmentioning

confidence: 99%

Multiple mitochondria-targeted components screened from Sini decoction improved cardiac energetics and mitochondrial dysfunction to attenuate doxorubicin-induced cardiomyopathy

Ding¹,

Zhang²,

Pan³

et al. 2023

Theranostics

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“…Tumour cells prefer the fatty acid oxidation pathway as a source of energy, which can come from either external or newly formed fatty acids, which are oxidised and stored as lipid droplets in the tissue. Fatty acid oxidation has been proven to protects cancer cells from treatment induced apoptosis by increasing mitochondrial membrane lipids [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

The contribution of the 1H-MRS lipid signal to cervical cancer prognosis: a preliminary study

et al. 2022

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Background The aim of this study was to investigate the role of the lipid peak derived from 1H magnetic resonance (MR) spectroscopy in assessing cervical cancer prognosis, particularly in assessing response to neoadjuvant chemotherapy (NACT) of locally advanced cervical cancer (LACC). Methods We enrolled 17 patients with histologically proven cervical cancer who underwent 3-T MR imaging at baseline. In addition to conventional imaging sequences for pelvic assessment, the protocol included a single-voxel point-resolved spectroscopy (PRESS) sequence, with repetition time of 1,500 ms and echo times of 28 and 144 ms. Spectra were analysed using the LCModel fitting routine, thus extracting multiple metabolites, including lipids (Lip) and total choline (tCho). Patients with LACC were treated with NACT and reassessed by MRI at term. Based on tumour volume reduction, patients were classified as good responder (GR; tumour volume reduction > 50%) and poor responder or nonresponder (PR-or-NR; tumour volume reduction ≤ 50%). Results Of 17 patients, 11 were LACC. Of these 11, only 6 had both completed NACT and had good-quality 1H-MR spectra; 3 GR and 3 PR-or-NR. A significant difference in lipid values was observed in the two groups of patients, particularly with higher Lip values and higher Lip/tCho ratio in PR-NR patients (p =0.040). A significant difference was also observed in choline distribution (tCho), with higher values in GR patients (p = 0.040). Conclusions Assessment of lipid peak at 1H-MR spectroscopy could be an additional quantitative parameter in predicting the response to NACT in patients with LACC.

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“…The results suggested that key genes for the development of breast cancer were directly involved in the biological processes associated with FAs. Li et al (2022) demonstrated that elevated fatty acid oxidation (FAO) activates STAT3 via acetylation of acetyl coenzyme A (CoA). The acetylation of STAT3 stimulates the expression of long-chain acyl coenzyme A synthase 4 (ACSL4), which increases phospholipid synthesis.…”

Section: Immune Infiltration Analysismentioning

confidence: 99%

Construction of a fatty acid metabolism-related gene signature for predicting prognosis and immune response in breast cancer

Liu

et al. 2023

Front. Genet.

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Background: Breast cancer has the highest incidence among malignant tumors in women, and its prevalence ranks first in global cancer morbidity.Aim: This study aimed to explore the feasibility of a prognostic model for patients with breast cancer based on the differential expression of genes related to fatty acid metabolism.Methods: The mRNA expression matrix of breast cancer and paracancer tissues was downloaded from The Cancer Genome Atlas database. The differentially expressed genes related to fatty acid metabolism were screened in R language. The TRRUST database was used to predict transcriptional regulators related to hub genes and construct an mRNA–transcription factor interaction network. A consensus clustering approach was used to identify different fatty acid regulatory patterns. In combination with patient survival data, Lasso and multivariate Cox proportional risk regression models were used to establish polygenic prognostic models based on fatty acid metabolism. The median risk score was used to categorize patients into high- and low-risk groups. Kaplan–Meier survival curves were used to analyze the survival differences between both groups. The Cox regression analysis included risk score and clinicopathological factors to determine whether risk score was an independent risk factor. Models based on genes associated with fatty acid metabolism were evaluated using receiver operating characteristic curves. A comparison was made between risk score levels and the fatty acid metabolism-associated genes in different subtypes of breast cancer. The differential gene sets of the Kyoto Encyclopedia of Genes and Genomes for screening high- and low-risk populations were compared using a gene set enrichment analysis. Furthermore, we utilized CIBERSORT to examine the abundance of immune cells in breast cancer in different clustering models.Results: High expression levels of ALDH1A1 and UBE2L6 prevented breast cancer, whereas high RDH16 expression levels increased its risk. Our comprehensive assessment of the association between prognostic risk scoring models and tumor microenvironment characteristics showed significant differences in the abundance of various immune cells between high- and low-risk breast cancer patients.Conclusions: By assessing fatty acid metabolism patterns, we gained a better understanding of the infiltration characteristics of the tumor microenvironment. Our findings are valuable for prognosis prediction and treatment of patients with breast cancer based on their clinicopathological characteristics.

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Fatty acid oxidation protects cancer cells from apoptosis by increasing mitochondrial membrane lipids

Cited by 44 publications

References 72 publications

Multiple mitochondria-targeted components screened from Sini decoction improved cardiac energetics and mitochondrial dysfunction to attenuate doxorubicin-induced cardiomyopathy

Multiple mitochondria-targeted components screened from Sini decoction improved cardiac energetics and mitochondrial dysfunction to attenuate doxorubicin-induced cardiomyopathy

The contribution of the 1H-MRS lipid signal to cervical cancer prognosis: a preliminary study

Construction of a fatty acid metabolism-related gene signature for predicting prognosis and immune response in breast cancer

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