Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes

Background: Vitamin C (Vit C) is an important physiological antioxidant with growing applications in cancer. Somatostatin (SST) is a natural peptide with growth inhibitory effect in several mammary cancer models. Objective: The combined effects of SST and Vit C supplementation have never been studied in breast cancer cells so far. Methods: We used MCF-7 and MDA-MB231 breast cancer cells incubated with SST for 24h, in the absence and presence of Vit C, at their EC50 concentrations, to evaluate membrane fatty acid-profiles together with the follow-up of EGFR and MAPK signaling pathways. Results: The two cell lines gave different membrane reorganization: in MCF-7 cells, decrease of omega-6 linoleic acid and increase of omega-3 fatty acids (Fas) occurred after SST and SST+Vit C incubations, the latter also showing significant increases in MUFA, docosapentaenoic acid and mono-trans arachidonic acid levels. In MDA-MB231 cells, SST+Vit C incubation induced significant membrane remodeling with an increase of stearic acid and mono-trans-linoleic acid isomer, diminution of omega-6 linoleic, arachidonic acid and omega-3 (docosapentaenoic and docosadienoic acids). Distinct signaling pathways in these cell lines were studies: in MCF-7 cells, incubations with SST and Vit C, alone or in combination significantly decreased EGFR and MAPK signaling, whereas in MDA-MB231 cells, SST and Vit C incubations, alone or combined, decreased p-P44/42 MAPK levels, and increased EGFR levels. Conclusion: Our results showed that SST and Vit C can be combined to induce membrane fatty acid changes, including lipid isomerization through a specific free radical-driven process, influencing signaling pathways.

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Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0352 ◽

2020 ◽

Vol 98 (3) ◽

pp. 131-138 ◽

Cited By ~ 3

Author(s):

Aysegul Hanikoglu ◽

Ertan Kucuksayan ◽

Ferhat Hanikoglu ◽

Tomris Ozben ◽

Georgia Menounou ◽

...

Keyword(s):

Breast Cancer ◽

Fatty Acid ◽

Signaling Pathways ◽

Cell Lines ◽

Fatty Acid Profile ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Mapk Signaling ◽

Membrane Fatty Acid ◽

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Breast cancer is a worldwide commonly found malignancy in women and effective treatment is regarded as a huge clinical challenge even in the presence of several treatment options. Extensive literature is available demonstrating polyphenols as phytopharmaceutical anticancer agents. Among the polyphenols, quercetin and curcumin have been reported to have a strong potential against breast cancer. However, so far, no comprehensive study has been performed to demonstrate the anticarcinogenic effects of curcumin, quercetin, and their combinations with somatostatin on the fatty acid profile of breast cancer cell membranes. We used MCF-7 and MDA-MB231 breast cancer cells incubated with curcumin and quercetin for 24 h, in the absence and presence of somatostatin, at their EC50 concentrations to evaluate membrane fatty acid based functional lipidomics together with the followup of EGFR and MAPK signaling pathways. The two cell lines gave different membrane free fatty acid reorganization. In MCF-7 cells, the following changes were observed: an increase of ω6 linoleic acid in the cells incubated with somatostatin + quercetin and quercetin and a decrease of ω3 acids in the cells incubated with somatostatin + curcumin compared to somatostatin and significant increases of monounsaturated fatty acid (MUFA), mono-trans arachidonic acid levels and docosapentaenoic acid for the cells incubated with somatostatin + quercetin compared to the control cells. In MDA-MB231 cells, incubations with curcumin, quercetin, and somatostatin + quercetin induced the most significant membrane remodeling with the increase of stearic acid, diminution of ω6 linoleic, arachidonic acids, and ω3 (docosapentaenoic and docosahexaenoic acids). Distinct signaling pathway changes were found for these cell lines. In MCF-7 cells, separate or combined incubations with somatostatin and quercetin, significantly decreased EGFR and incubation with curcumin decreased MAPK signaling. In MDA-MB231 cells, incubation with curcumin decreased AKT1 and p-AKT1 (Thr308) levels. Incubation with curcumin and quercetin decreased the EGFR levels. Our results showed that cytostatic and antioxidant treatments can be combined to induce membrane fatty acid changes, including lipid isomerization as specific free radical driven process, and to influence signaling pathways. This study aimed to contribute to the literature on these antioxidants in the treatment of breast cancer to clarify the effects and mechanisms in combination with somatostatin.

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Bag-1 silencing enhanced chemotherapeutic drug-induced apoptosis in MCF-7 breast cancer cells affecting PI3K/Akt/mTOR and MAPK signaling pathways

Molecular Biology Reports ◽

10.1007/s11033-018-4540-x ◽

2019 ◽

Vol 46 (1) ◽

pp. 847-860 ◽

Cited By ~ 6

Author(s):

Pelin Ozfiliz Kilbas ◽

Izzet Mehmet Akcay ◽

Gizem Dinler Doganay ◽

Elif Damla Arisan

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Signaling Pathways ◽

Breast Cancer Cells ◽

Mapk Signaling ◽

Chemotherapeutic Drug ◽

Drug Induced ◽

Induced Apoptosis ◽

Mapk Signaling Pathways ◽

Mcf 7

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Alantolactone induces apoptosis and suppresses migration in MCF‑7 human breast cancer cells via the p38�MAPK, NF‑κB and Nrf2 signaling pathways

International Journal of Molecular Medicine ◽

10.3892/ijmm.2018.3751 ◽

2018 ◽

Cited By ~ 1

Author(s):

Jianli Liu ◽

Meijia Liu ◽

Shuai Wang ◽

Yin He ◽

Yapeng Huo ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Signaling Pathways ◽

P38 Mapk ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Mcf 7

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Orientin inhibits invasion by suppressing MMP-9 and IL-8 expression via the PKCα/ ERK/AP-1/STAT3-mediated signaling pathways in TPA-treated MCF-7 breast cancer cells

Phytomedicine ◽

10.1016/j.phymed.2018.09.172 ◽

2018 ◽

Vol 50 ◽

pp. 35-42 ◽

Cited By ~ 7

Author(s):

Soo-Jin Kim ◽

Thu-Huyen Pham ◽

Yesol Bak ◽

Hyung-Won Ryu ◽

Sei-Ryang Oh ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Signaling Pathways ◽

Breast Cancer Cells ◽

Mcf 7

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Identification of hub genes associated with RNAi-induced silencing of XIAP through targeted proteomics approach in MCF7 cells

Cell & Bioscience ◽

10.1186/s13578-020-00437-9 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 2

Author(s):

Mehdi Agha Gholizadeh ◽

Fatemeh T. Shamsabadi ◽

Ahad Yamchi ◽

Masoud Golalipour ◽

Gagan Deep Jhingan ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Specific Antigen ◽

Mapk Signaling ◽

2D Electrophoresis ◽

Mcf7 Cells ◽

Apoptosis Pathway ◽

Apoptosis Protein ◽

Mcf 7

Abstract Background The X-linked inhibitor of apoptosis protein (XIAP) is the most potent caspase inhibitor of the IAP family in apoptosis pathway. This study aims to identify the molecular targets of XIAP in human breast cancer cells exposed to XIAP siRNA by proteomics screening. The expression of XIAP was reduced in MCF-7 breast cancer cells by siRNA. Cell viability and the mRNA expression level of this gene were evaluated by MTS and quantitative real-time PCR procedures, respectively. Subsequently, the XIAP protein level was visualized by Western blotting and analyzed by two-dimensional (2D) electrophoresis and LC–ESI–MS/MS. Results Following XIAP silencing, cell proliferation was reduced in XIAP siRNA transfected cells. The mRNA transcription and protein expression of XIAP were decreased in cells exposed to XIAP siRNA than si-NEG. We identified 30 proteins that were regulated by XIAP, of which 27 down-regulated and 3 up-regulated. The most down-regulated proteins belonged to the Heat Shock Proteins family. They participate in cancer related processes including apoptosis and MAPK signaling pathway. Reduced expression of HSP90B1 was associated with apoptosis induction by androgen receptor and prostate specific antigen. Suppression of XIAP resulted in the enhancement of GDIB, ENO1, and CH60 proteins expression. The network analysis of XIAP-regulated proteins identified HSPA8, HSP90AA1, ENO1, and HSPA9 as key nodes in terms of degree and betweenness centrality methods. Conclusions These results suggested that XIAP may have a number of biological functions in a diverse set of non-apoptotic signaling pathways and may provide an insight into the biomedical significance of XIAP over-expression in MCF-7 cells.

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