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Article ; Online: The Involvement of Polyunsaturated Fatty Acids in Apoptosis Mechanisms and Their Implications in Cancer.

Montecillo-Aguado, Mayra / Tirado-Rodriguez, Belen / Huerta-Yepez, Sara

International journal of molecular sciences

2023 Volume 24, Issue 14

Abstract: Cancer is a significant global public health issue and, despite advancements in detection and treatment, the prognosis remains poor. Cancer is a complex disease characterized by various hallmarks, including dysregulation in apoptotic cell death pathways. ...

Abstract	Cancer is a significant global public health issue and, despite advancements in detection and treatment, the prognosis remains poor. Cancer is a complex disease characterized by various hallmarks, including dysregulation in apoptotic cell death pathways. Apoptosis is a programmed cell death process that efficiently eliminates damaged cells. Several studies have indicated the involvement of polyunsaturated fatty acids (PUFAs) in apoptosis, including omega-3 PUFAs such as alpha-linolenic acid, docosahexaenoic acid, and eicosapentaenoic acid. However, the role of omega-6 PUFAs, such as linoleic acid, gamma-linolenic acid, and arachidonic acid, in apoptosis is controversial, with some studies supporting their activation of apoptosis and others suggesting inhibition. These PUFAs are essential fatty acids, and Western populations today have a high consumption rate of omega-6 to omega-3 PUFAs. This review focuses on presenting the diverse molecular mechanisms evidence in both in vitro and in vivo models, to help clarify the controversial involvement of omega-3 and omega-6 PUFAs in apoptosis mechanisms in cancer.
MeSH term(s)	Humans ; Fatty Acids, Unsaturated ; Fatty Acids, Omega-3 ; Fatty Acids, Omega-6 ; Docosahexaenoic Acids ; Apoptosis ; Neoplasms
Chemical Substances	Fatty Acids, Unsaturated ; Fatty Acids, Omega-3 ; Fatty Acids, Omega-6 ; Docosahexaenoic Acids (25167-62-8)
Language	English
Publishing date	2023-07-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241411691
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: KLF4 inhibition by Kenpaullone induces cytotoxicity and chemo sensitization in B-NHL cell lines via YY1 independent.

Montecillo-Aguado, Mayra / Morales-Martínez, Mario / Huerta-Yepez, Sara / Vega, Mario I

Leukemia & lymphoma

2021 Volume 62, Issue 6, Page(s) 1422–1431

Abstract: Krüppel-like factor 4 (KLF4) is a member of the KLF transcription factor family containing zinc-fingers, and is involved in the regulation of apoptosis, proliferation and differentiation of B cells and B-cell malignancies. KLF4 can act like an oncogene, ... ...

Abstract	Krüppel-like factor 4 (KLF4) is a member of the KLF transcription factor family containing zinc-fingers, and is involved in the regulation of apoptosis, proliferation and differentiation of B cells and B-cell malignancies. KLF4 can act like an oncogene, we shown that KLF4 overexpression correlated with poor prognostic and chemoresistance in B-NHL. In addition, we shown that KLF4 is regulated by YY1. In this study, we demonstrate that chemical inhibition of KLF4 by Kenpaullone, results in suppression of proliferation, cell survival, downregulation of Bcl-2 and increases apoptosis in B-NHL cell lines through YY1 independent pathway. Combination of Kenpaullone and Doxorubicin, increased apoptosis. The co-expressions of KLF4/YY1 or KLF4/Bcl-2 in NHL was analyzed using Oncomine Database, exhibiting a positive correlation of expression. The present findings suggest that the chemical inhibition of KLF4 by Kenpaullone treatment could be a potential therapeutic alternatively in KLF4
MeSH term(s)	Apoptosis ; B-Lymphocytes ; Benzazepines ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Indoles ; Kruppel-Like Factor 4 ; Kruppel-Like Transcription Factors/genetics ; Lymphoma/drug therapy
Chemical Substances	Benzazepines ; Indoles ; KLF4 protein, human ; Kruppel-Like Factor 4 ; Kruppel-Like Transcription Factors ; kenpaullone
Language	English
Publishing date	2021-01-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2020.1869960
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Article: Antineoplastic effect of compounds C14 and P8 on TNBC and radioresistant TNBC cells by stabilizing the K-Ras4B

Carrión-Estrada, Dayan A / Aguilar-Rojas, Arturo / Huerta-Yepez, Sara / Montecillo-Aguado, Mayra / Bello, Martiniano / Rojo-Domínguez, Arturo / Arechaga-Ocampo, Elena / Briseño-Díaz, Paola / Meraz-Ríos, Marco Antonio / Thompson-Bonilla, María Del Rocío / Hernández-Rivas, Rosaura / Vargas, Miguel

Frontiers in oncology

2024 Volume 14, Page(s) 1341766

Abstract: Introduction: Breast cancer (BC) is the leading cause of cancer-related deaths among women, with triple-negative breast cancer (TNBC) representing one of the most aggressive and treatment-resistant subtypes. In this study, we aimed to evaluate the ... ...

Abstract	Introduction: Breast cancer (BC) is the leading cause of cancer-related deaths among women, with triple-negative breast cancer (TNBC) representing one of the most aggressive and treatment-resistant subtypes. In this study, we aimed to evaluate the antitumor potential of C14 and P8 molecules in both TNBC and radioresistant TNBC cells. These compounds were chosen for their ability to stabilize the complex formed by the overactivated form of K-Ras4B Methods: The antitumor potential of C14 and P8 was assessed using TNBC cell lines, MDA-MB-231, and the radioresistant derivative MDA-MB-231RR, both carrying the K-Ras4B> Results: Western blotting analysis determined the negative impact of C14 and P8 on the activation of mutant K-Ras signaling pathways in MDA-MB-231 and MDA-MB-231RR cells. Proliferation assays demonstrated their efficacy as cytotoxic agents against K-Ras Discussion: These findings suggest that C14 and P8 could serve as promising adjuvant treatments for TNBC, particularly for non-responders to standard therapies. By targeting overactivated K-Ras and its membrane transporter, these compounds offer potential therapeutic benefits against TNBC, including its radioresistant form. Further research and clinical trials are warranted to validate their efficacy and safety as novel TNBC treatments.
Language	English
Publishing date	2024-03-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2024.1341766
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Article ; Online: Omega-6 Polyunsaturated Fatty Acids Enhance Tumor Aggressiveness in Experimental Lung Cancer Model: Important Role of Oxylipins.

Montecillo-Aguado, Mayra / Tirado-Rodriguez, Belen / Antonio-Andres, Gabriela / Morales-Martinez, Mario / Tong, Zhen / Yang, Jun / Hammock, Bruce D / Hernandez-Pando, Rogelio / Huerta-Yepez, Sara

International journal of molecular sciences

2022 Volume 23, Issue 11

Abstract: Lung cancer is currently the leading cause of cancer death worldwide; it is often diagnosed at an advanced stage and bears poor prognosis. It has been shown that diet is an important environmental factor that contributes to the risk and mortality of ... ...

Abstract	Lung cancer is currently the leading cause of cancer death worldwide; it is often diagnosed at an advanced stage and bears poor prognosis. It has been shown that diet is an important environmental factor that contributes to the risk and mortality of several types of cancers. Intake of ω-3 and ω-6 PUFAs plays an important role in cancer risk and progression. Current Western populations have high consumption of ω-6 PUFAs with a ratio of ω-6/ω-3 PUFAs at 15:1 to 16.7:1 This high consumption of ω-6 PUFAs is related to increased cancer risk and progression. However, whether a diet rich in ω-6 PUFAs can contribute to tumor aggressiveness has not been well investigated. We used a murine model of pulmonary squamous cell carcinoma to study the aggressiveness of tumors in mice fed with a diet rich in ω-6 PUFAs and its relationship with oxylipins. Our results shown that the mice fed a diet rich in ω-6 showed a marked increase in proliferation, angiogenesis and pro-inflammatory markers and decreased expression of pro-apoptotic proteins in their tumors. Oxylipin profiling revealed an upregulation of various pro-tumoral oxylipins including PGs, HETEs, DiHETrEs and HODEs. These results demonstrate for the first time that high intake of ω-6 PUFAs in the diet enhances the malignancy of tumor cells by histological changes on tumor dedifferentiation and increases cell proliferation, angiogenesis, pro-inflammatory oxylipins and molecular aggressiveness targets such as NF-κB p65, YY1, COX-2 and TGF-β.
MeSH term(s)	Animals ; Diet ; Fatty Acids, Omega-3/metabolism ; Fatty Acids, Omega-3/pharmacology ; Fatty Acids, Omega-6/metabolism ; Fatty Acids, Omega-6/pharmacology ; Lung Neoplasms ; Mice ; Oxylipins/metabolism
Chemical Substances	Fatty Acids, Omega-3 ; Fatty Acids, Omega-6 ; Oxylipins
Language	English
Publishing date	2022-05-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23116179
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Article ; Online: Aryl Hydrocarbon Receptor-Dependent inductions of omega-3 and omega-6 polyunsaturated fatty acid metabolism act inversely on tumor progression.

Huerta-Yepez, Sara / Tirado-Rodriguez, Ana / Montecillo-Aguado, Mayra R / Yang, Jun / Hammock, Bruce D / Hankinson, Oliver

Scientific reports

2020 Volume 10, Issue 1, Page(s) 7843

Abstract: The Western diet contains a high ratio of omega-6 (ω6) to omega-3 (ω3) polyunsaturated fatty acids (PUFA). The prototypical aryl hydrocarbon receptor (AHR) ligand, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), induces CYP1 family enzymes, which can ... ...

Abstract	The Western diet contains a high ratio of omega-6 (ω6) to omega-3 (ω3) polyunsaturated fatty acids (PUFA). The prototypical aryl hydrocarbon receptor (AHR) ligand, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), induces CYP1 family enzymes, which can metabolize PUFA to epoxides. Mice fed ω3-rich or ω6-rich diets were treated with TCDD and injected subcutaneously with AHR-competent Hepa1-GFP hepatoma cells or AHR-deficient LLC lung cancer cells. TCDD reduced the growth rates of the resulting tumors in ω3-fed mice and inhibited their metastasis to the liver and/or lung, but had the opposite effects in mice fed ω6 PUFA. These responses were likely attributable to the corresponding PUFA epoxides generated in tumor cells and/or host, since many depended upon co-administration of a soluble epoxide hydrolase (EPHX2) inhibitor in males, and/or were associated with increases in epoxide levels in tumors and sites of metastasis. Equivalent effects occurred in females in the absence of EPHX2 inhibition, probably because this sex expressed reduced levels of EPHX2. The responses elicited by TCDD were associated with effects on tumor vascularity, tumor cell proliferation and/or apoptosis. Thus environmental AHR agonists, and potentially also endogenous, nutritional, and microbiome-derived agonists, may reduce or enhance cancer progression depending on the composition of dietary PUFA, particularly in females.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Cell Count ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Transformation, Neoplastic ; Diet ; Disease Progression ; Fatty Acids, Omega-3/metabolism ; Fatty Acids, Omega-3/pharmacology ; Fatty Acids, Omega-6/metabolism ; Fatty Acids, Omega-6/pharmacology ; Female ; Humans ; Lung Neoplasms/pathology ; Male ; Mice ; Receptors, Aryl Hydrocarbon/metabolism ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Fatty Acids, Omega-3 ; Fatty Acids, Omega-6 ; Receptors, Aryl Hydrocarbon ; Vascular Endothelial Growth Factor A
Language	English
Publishing date	2020-05-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-64146-6
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Article: Importance of the Role of ω-3 and ω-6 Polyunsaturated Fatty Acids in the Progression of Brain Cancer.

Montecillo-Aguado, Mayra / Tirado-Rodriguez, Belen / Tong, Zhen / Vega, Owen M / Morales-Martínez, Mario / Abkenari, Shaheen / Pedraza-Chaverri, José / Huerta-Yepez, Sara

Brain sciences

2020 Volume 10, Issue 6

Abstract: Brain cancer is one of the most malignant types of cancer in both children and adults. Brain cancer patients tend to have a poor prognosis and a high rate of mortality. Additionally, 20-40% of all other types of cancer can develop brain metastasis. ... ...

Abstract	Brain cancer is one of the most malignant types of cancer in both children and adults. Brain cancer patients tend to have a poor prognosis and a high rate of mortality. Additionally, 20-40% of all other types of cancer can develop brain metastasis. Numerous pieces of evidence suggest that omega-3-polyunsaturated fatty acids (ω-PUFAs) could potentially be used in the prevention and therapy of several types of cancer. PUFAs and oxylipins are fundamental in preserving physiological events in the nervous system; it is, therefore, necessary to maintain a certain ratio of ω-3 to ω-6 for normal nervous system function. Alterations in PUFAs signaling are involved in the development of various pathologies of the nervous system, including cancer. It is well established that an omega-6-polyunsaturated fatty acid (ω-6 PUFA)-rich diet has a pro-tumoral effect, whereas the consumption of an ω-3 rich diet has an anti-tumoral effect. This review aims to offer a better understanding of brain cancer and PUFAs and to discuss the role and impact of PUFAs on the development of different types of brain cancer. Considering the difficulty of antitumor drugs in crossing the blood-brain barrier, the therapeutic role of ω-3/ω-6 PUFAs against brain cancer would be a good alternative to consider. We highlight our current understanding of the role of PUFAs and its metabolites (oxylipins) in different brain tumors, proliferation, apoptosis, invasion, angiogenesis, and immunosuppression by focusing on recent research in vitro and in vivo.
Language	English
Publishing date	2020-06-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci10060381
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Article: p21-Activated Kinase 1 Promotes Breast Tumorigenesis

Saldivar-Cerón, Héctor I / Villamar-Cruz, Olga / Wells, Claire M / Oguz, Ibrahim / Spaggiari, Federica / Chernoff, Jonathan / Patiño-López, Genaro / Huerta-Yepez, Sara / Montecillo-Aguado, Mayra / Rivera-Pazos, Clara M / Loza-Mejía, Marco A / Vivar-Sierra, Alonso / Briseño-Díaz, Paola / Zentella-Dehesa, Alejandro / Leon-Del-Rio, Alfonso / López-Saavedra, Alejandro / Padierna-Mota, Laura / Ibarra-Sánchez, María de Jesús / Esparza-López, José /

Hernández-Rivas, Rosaura / Arias-Romero, Luis E

Frontiers in cell and developmental biology

2022 Volume 9, Page(s) 759259

Abstract: p21-Activated kinase-1 (Pak1) is frequently overexpressed and/or amplified in human breast cancer and is necessary for transformation of mammary epithelial cells. Here, we show that Pak1 interacts with and phosphorylates the Calcium/Calmodulin-dependent ... ...

Abstract	p21-Activated kinase-1 (Pak1) is frequently overexpressed and/or amplified in human breast cancer and is necessary for transformation of mammary epithelial cells. Here, we show that Pak1 interacts with and phosphorylates the Calcium/Calmodulin-dependent Protein Kinase II (CaMKII), and that pharmacological inhibition or depletion of Pak1 leads to diminished activity of CaMKII. We found a strong correlation between Pak1 and CaMKII expression in human breast cancer samples, and combined inhibition of Pak1 and CaMKII with small-molecule inhibitors was synergistic and induced apoptosis more potently in Her2 positive and triple negative breast cancer (TNBC) cells. Co-adminstration of Pak and CaMKII small-molecule inhibitors resulted in a dramatic reduction of proliferation and an increase in apoptosis in a 3D cell culture setting, as well as an impairment in migration and invasion of TNBC cells. Finally, mice bearing xenografts of TNBC cells showed a significant delay in tumor growth when treated with small-molecule inhibitors of Pak and CaMKII. These data delineate a signaling pathway from Pak1 to CaMKII that is required for efficient proliferation, migration and invasion of mammary epithelial cells, and suggest new therapeutic strategies in breast cancer.
Language	English
Publishing date	2022-01-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.759259
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Article ; Online: Cross-Reaction, Enhancement, and Neutralization Activity of Dengue Virus Antibodies against Zika Virus: A Study in the Mexican Population.

Montecillo-Aguado, Mayra R / Montes-Gómez, Alfredo E / García-Cordero, Julio / Corzo-Gómez, Josselin / Vivanco-Cid, Héctor / Mellado-Sánchez, Gabriela / Muñoz-Medina, J Esteban / Gutiérrez-Castañeda, Benito / Santos-Argumedo, Leopoldo / González-Bonilla, César / Cedillo-Barrón, Leticia

Journal of immunology research

2019 Volume 2019, Page(s) 7239347

Abstract: Zika virus (ZIKV), an emerging mosquito-borne flavivirus, has quickly spread in many regions around the world where dengue virus (DENV) is endemic. This represents a major health concern, given the high homology between these two viruses, which can ... ...

Abstract	Zika virus (ZIKV), an emerging mosquito-borne flavivirus, has quickly spread in many regions around the world where dengue virus (DENV) is endemic. This represents a major health concern, given the high homology between these two viruses, which can result in cross-reactivity. The aim of this study was to determine the cross-reacting antibody response of the IgM and IgG classes against the recombinant envelope protein of ZIKV (rE-ZIKV) in sera from patients with acute-phase infection of different clinical forms of dengue, i.e., dengue fever (DF) and dengue hemorrhagic fever (DHF) (before the arrival of ZIKV in Mexico 2010), as well as acute-phase sera of ZIKV patients, together with the implications in neutralization and antibody-dependent enhancement. Differences in IgM responses were observed in a number of DF and DHF patients whose sera cross-reacted with the rE-ZIK antigen, with 42% recognition between acute-phase DHF and ZIKV but 27% recognition between DF and ZIKV. Regarding IgG antibodies, 71.5% from the DF group showed cross-reactivity to rE-ZIKV in contrast with 50% and only 25% of DHF and ZIKV serum samples, respectively, which specifically recognized the homologous antigen. The DHF group showed more enhancement of ZIKV infection of FCR
MeSH term(s)	Adolescent ; Adult ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Cell Line ; Child ; Child, Preschool ; Cross Reactions/immunology ; Dengue/epidemiology ; Dengue/immunology ; Dengue Virus/genetics ; Dengue Virus/immunology ; Female ; Humans ; Male ; Mexico/epidemiology ; Middle Aged ; Neutralization Tests ; Population Surveillance ; Young Adult ; Zika Virus/genetics ; Zika Virus/immunology ; Zika Virus Infection/epidemiology ; Zika Virus Infection/immunology
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2019-09-02
Publishing country	Egypt
Document type	Journal Article
ZDB-ID	2817541-4
ISSN	2314-7156 ; 2314-8861
ISSN (online)	2314-7156
ISSN	2314-8861
DOI	10.1155/2019/7239347
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Article ; Online: The Involvement of Polyunsaturated Fatty Acids in Apoptosis Mechanisms and Their Implications in Cancer.

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Article ; Online: KLF4 inhibition by Kenpaullone induces cytotoxicity and chemo sensitization in B-NHL cell lines via YY1 independent.

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Article: Antineoplastic effect of compounds C14 and P8 on TNBC and radioresistant TNBC cells by stabilizing the K-Ras4B

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Article ; Online: Omega-6 Polyunsaturated Fatty Acids Enhance Tumor Aggressiveness in Experimental Lung Cancer Model: Important Role of Oxylipins.

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Article ; Online: Aryl Hydrocarbon Receptor-Dependent inductions of omega-3 and omega-6 polyunsaturated fatty acid metabolism act inversely on tumor progression.

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Article: Importance of the Role of ω-3 and ω-6 Polyunsaturated Fatty Acids in the Progression of Brain Cancer.

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Article: p21-Activated Kinase 1 Promotes Breast Tumorigenesis

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Article ; Online: Cross-Reaction, Enhancement, and Neutralization Activity of Dengue Virus Antibodies against Zika Virus: A Study in the Mexican Population.

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