Multifunctional Role of Lipids in Modulating the Tumorigenic Properties of 4T1 Breast Cancer Cells

He, Yuanyuan; Rezaei, Somayeh; Júnior, Raimundo Fernandes de Araújo; Cruz, Luis J.; Eich, Christina

doi:10.3390/ijms23084240

Cited by 7 publications

(6 citation statements)

References 97 publications

(111 reference statements)

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“…Lipids are key metabolites in the process of macrophage polarization, and lipid metabolism has important influences on the polarization of macrophages. Analysis of lipid metabolite content in M2-like TAM before and after dCP1 intervention revealed M2-like TAM after treatment with glycopeptides, the lipid metabolites like SM, Cer [ 69 , 95 – 98 ], TG, DG, MG [ 99 – 101 ], LPS [ 102 ], etc., which were at higher content levels in M1 phenotype than in M2 phenotype or pro-inflammatory lipid metabolites were increased; and lipid metabolites like PS [ 103 , 104 ], Pet, PI, PC [ 68 – 70 ], etc., which were at higher content levels in M2 phenotype than in M1 phenotype were decreased. The M2-like TAM polarized toward the M1 phenotype after treatment with the glycopeptide dCP1 when compared with the lipid metabolic profile of M1 phenotype macrophages.…”

Section: Discussionmentioning

confidence: 99%

Codonopsis pilosula-derived glycopeptide dCP1 promotes the polarization of tumor-associated macrophage from M2-like to M1 phenotype

Liu,

Yao,

Ren

2024

Cancer Immunol Immunother

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The majority of the immune cell population in the tumor microenvironment (TME) consists of tumor-associated macrophages (TAM), which are the main players in coordinating tumor-associated inflammation. TAM has a high plasticity and is divided into two main phenotypes, pro-inflammatory M1 type and anti-inflammatory M2 type, with tumor-suppressive and tumor-promoting functions, respectively. Considering the beneficial effects of M1 macrophages for anti-tumor and the high plasticity of macrophages, the conversion of M2 TAM to M1 TAM is feasible and positive for tumor treatment. This study sought to evaluate whether the glycopeptide derived from simulated digested Codonopsis pilosula extracts could regulate the polarization of M2-like TAM toward the M1 phenotype and the potential regulatory mechanisms. The results showed that after glycopeptide dCP1 treatment, the mRNA relative expression levels of some M2 phenotype marker genes in M2-like TAM in simulated TME were reduced, and the relative expression levels of M1 phenotype marker genes and inflammatory factor genes were increased. Analysis of RNA-Seq of M2-like TAM after glycopeptide dCP1 intervention showed that the gene sets such as glycolysis, which is associated with macrophage polarization in the M1 phenotype, were significantly up-regulated, whereas those of gene sets such as IL-6-JAK-STAT3 pathway, which is associated with polarization in the M2 phenotype, were significantly down-regulated. Moreover, PCA analysis and Pearson's correlation also indicated that M2-like TAM polarized toward the M1 phenotype at the transcriptional level after treatment with the glycopeptide dCP1. Lipid metabolomics was used to further explore the efficacy of the glycopeptide dCP1 in regulating the polarization of M2-like TAM to the M1 phenotype. It was found that the lipid metabolite profiles in dCP1-treated M2-like TAM showed M1 phenotype macrophage lipid metabolism profiles compared with blank M2-like TAM. Analysis of the key differential lipid metabolites revealed that the interconversion between phosphatidylcholine (PC) and diacylglycerol (DG) metabolites may be the central reaction of the glycopeptide dCP1 in regulating the conversion of M2-like TAM to the M1 phenotype. The above results suggest that the glycopeptide dCP1 has the efficacy to regulate the polarization of M2-like TAM to M1 phenotype in simulated TME.

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Section: Discussionmentioning

confidence: 99%

Codonopsis pilosula-derived glycopeptide dCP1 promotes the polarization of tumor-associated macrophage from M2-like to M1 phenotype

Liu,

Yao,

Ren

2024

Cancer Immunol Immunother

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“…Moreover, studies have shown that PA can exert an anti-tumor effect by modulating the polarization of tumorassociated macrophages (TAMs) towards an M2 phenotype, thereby impeding EMT in M2 macrophages (44). He et al (71) demonstrated that PA has the ability to inhibit the proliferation and metastasis of 4T1 breast cancer cells. This effect was achieved by downregulating the mRNA levels of Nfkb1, Snai1, and Stat3, reducing the expression of the EMT marker vimentin, and increasing the expression of E-cadherin.…”

Section: Inhibition Of Tumor Cell Metastasis and Invasion In Response...mentioning

confidence: 99%

“…He et al. ( 71 ) demonstrated that PA has the ability to inhibit the proliferation and metastasis of 4T1 breast cancer cells. This effect was achieved by downregulating the mRNA levels of Nfkb1, Snai1, and Stat3, reducing the expression of the EMT marker vimentin, and increasing the expression of E-cadherin.…”

Section: Inhibition Of Tumor Cell Metastasis and Invasion In Response...mentioning

confidence: 99%

Molecular mechanism of palmitic acid and its derivatives in tumor progression

2023

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Palmitic acid (PA) is a saturated fatty acid commonly found in coconut oil and palm oil. It serves as an energy source for the body and plays a role in the structure and function of cell membranes. Beyond its industrial applications, PA has gained attention for its potential therapeutic properties. Modern pharmacological studies have demonstrated that PA exhibits anti-inflammatory, antioxidant, and immune-enhancing effects. In recent years, PA has emerged as a promising anti-tumor agent with demonstrated efficacy against various malignancies including gastric cancer, liver cancer, cervical cancer, breast cancer, and colorectal cancer. Its anti-tumor effects encompass inducing apoptosis in tumor cells, inhibiting tumor cell proliferation, suppressing metastasis and invasion, enhancing sensitivity to chemotherapy, and improving immune function. The main anticancer mechanism of palmitic acid (PA) involves the induction of cell apoptosis through the mitochondrial pathway, facilitated by the promotion of intracellular reactive oxygen species (ROS) generation. PA also exhibits interference with the cancer cell cycle, leading to cell cycle arrest predominantly in the G1 phase. Moreover, PA induces programmed cell autophagy death, inhibits cell migration, invasion, and angiogenesis, and synergistically enhances the efficacy of chemotherapy drugs while reducing adverse reactions. PA acts on various intracellular and extracellular targets, modulating tumor cell signaling pathways, including the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), endoplasmic reticulum (ER), B Cell Lymphoma-2 (Bcl-2), P53, and other signaling pathways. Furthermore, derivatives of PA play a significant regulatory role in tumor resistance processes. This paper provides a comprehensive review of recent studies investigating the anti-tumor effects of PA. It summarizes the underlying mechanisms through which PA exerts its anti-tumor effects, aiming to inspire new perspectives for the treatment of malignant tumors in clinical settings and the development of novel anti-cancer drugs.

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“…We selected PA (Figure 2a) as a stabilizer, because it is a biocompatible saturated fatty acid (FA), with a C16 chain found in animal and vegetable oils, which was reported for having intrinsic anti-tumour activity in a variety of tumour types, including colorectal, liver, prostate and breast cancer [20][21][22][23][24][25], as many other exogenous FAs, which were effective in overcoming drug resistance and metastasis in tumour cells [26,27].…”

Section: The Reasons Of Our Choicementioning

confidence: 99%

Imidazo-Pyrazole-Loaded Palmitic Acid and Polystyrene-Based Nanoparticles: Synthesis, Characterization and Antiproliferative Activity on Chemo-Resistant Human Neuroblastoma Cells

Valenti,

Marengo,

Milanese

et al. 2023

IJMS

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Neuroblastoma (NB) is a childhood cancer, commonly treated with drugs, such as etoposide (ETO), whose efficacy is limited by the onset of resistance. Here, aiming at identifying new treatments for chemo-resistant NB, the effects of two synthesized imidazo-pyrazoles (IMPs) (4G and 4I) were investigated on ETO-sensitive (HTLA-230) and ETO-resistant (HTLA-ER) NB cells, detecting 4I as the more promising compound, that demonstrated IC50 values lower than those of ETO on HTLA ER. Therefore, to further improve the activity of 4I, we developed 4I-loaded palmitic acid (PA) and polystyrene-based (P5) cationic nanoparticles (P5PA-4I NPs) with high drug loading (21%) and encapsulation efficiency (97%), by a single oil-in-water emulsification technique. Biocompatible PA was adopted as an emulsion stabilizer, while synthesized P5 acted as an encapsulating agent, solubilizer and hydrophilic–lipophilic balance (HLB) improver. Optic microscopy and cytofluorimetric analyses were performed to investigate the micromorphology, size and complexity distributions of P5PA-4I NPs, which were also structurally characterized by chemometric-assisted Fourier transform infrared spectroscopy (FTIR). Potentiometric titrations allowed us to estimate the milliequivalents of PA and basic nitrogen atoms present in NPs. P5PA-4I NPs afforded dispersions in water with excellent buffer capacity, essential to escape lysosomal degradation and promote long residence time inside cells. They were chemically stable in an aqueous medium for at least 40 days, while in dynamic light scattering (DLS) analyses, P5PA-4I showed a mean hydrodynamic diameter of 541 nm, small polydispersity (0.194), and low positive zeta potentials (+8.39 mV), assuring low haemolytic toxicity. Biological experiments on NB cells, demonstrated that P5PA-4I NPs induced ROS-dependent cytotoxic effects significantly higher than those of pristine 4I, showing a major efficacy compared to ETO in reducing cell viability in HTLA-ER cells. Collectively, this 4I-based nano-formulation could represent a new promising macromolecular platform to develop a new delivery system able to increase the cytotoxicity of the anticancer drugs.

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Multifunctional Role of Lipids in Modulating the Tumorigenic Properties of 4T1 Breast Cancer Cells

Cited by 7 publications

References 97 publications

Codonopsis pilosula-derived glycopeptide dCP1 promotes the polarization of tumor-associated macrophage from M2-like to M1 phenotype

Codonopsis pilosula-derived glycopeptide dCP1 promotes the polarization of tumor-associated macrophage from M2-like to M1 phenotype

Molecular mechanism of palmitic acid and its derivatives in tumor progression

Imidazo-Pyrazole-Loaded Palmitic Acid and Polystyrene-Based Nanoparticles: Synthesis, Characterization and Antiproliferative Activity on Chemo-Resistant Human Neuroblastoma Cells

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