Nadia Jacobo‐Herrera

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

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Carlos Pérez‐Plasencia

Autonomous University of Tlaxcala

César López‐Camarillo

Universidad Autónoma de la Ciudad de México

David Cantú de León

CHI Health

Eduardo López–Urrutia

Autonomous University of Tlaxcala

Alejandro Zentella‐Dehesa

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Jossimar Coronel-Hernández

Instituto Nacional de Cancerología

Verónica García-Castillo

Autonomous University of Tlaxcala

Oscar Peralta‐Zaragoza

Instituto Nacional de Salud Pública

Alma D. Campos-Parra

Universidad Veracruzana

Antonio Daniel Martínez-Gutiérrez

Instituto Nacional de Cancerología

Cooperative Institutions

Inserm

148

Centre National de la Recherche Scientifique

135

University of Michigan–Ann Arbor

126

Harvard University

118

Universidad Nacional Autónoma de México

105

Chinese Academy of Sciences

Istituti di Ricovero e Cura a Carattere Scientifico

National Institutes of Health

Consejo Superior de Investigaciones Científicas

Instituto de Salud Carlos III

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Antibacterial and Wound Healing Activity In Vitro of Individual and Combined Extracts of Tagetes nelsonii Greenm, Agave americana and Aloe vera

Scientia Pharmaceutica (2024)

Karen Alejandra Olán-Jiménez Rosa Isela Cruz‐Rodríguez Beatriz del Carmen Couder-García Nadia Jacobo‐Herrera Nancy Ruíz-Lau

Currently, there are various physical and mechanical agents that can cause skin wounds, which are still traditionally treated with plant extracts. It has been reported that the genus Tagetes has a wide range of biological properties, including antibacterial and wound healing activity. Likewise, Agave americana extract and Aloe vera gel have shown potential in the treatment of burn wounds and other skin conditions both in vitro and in vivo. In this study, the antibacterial and wound healing activities of each of these plants were investigated, as well as the possibility of enhancing these activities by combining them. First, the secondary metabolites of the extracts were quantified, the antibacterial activity was evaluated using the Kirby-Bauer method, and their cytotoxicity was measured in 3T3 and HaCaT cells using the sulforhodamine B assay. The results revealed that Tagetes nelsonii extract had a higher amount of secondary metabolites, which is why it exhibited antibacterial activity. Finally, the scratch assay showed that the individual extracts of T. nelsonii and A. americana demonstrated greater cell migration and proliferation starting from 12 h, as well as when using the combination of A. americana extract and A. vera gel, which almost completely closed the wound compared to the control.

Aloe Vera

HaCaT

Sulforhodamine B

Tagetes

Agave

10.3390/scipharm92030041

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Anti-inflammatory and Antitumor Activity of a Triple Therapy for a Colitis-Related Colorectal Cancer

Journal of Cancer (2016)

Gabriela Figueroa‐González Verónica García-Castillo Jossimar Coronel-Hernández Eduardo López–Urrutia Sonia León‐Cabrera

Colorectal cancer (CRC) is an important health issue worldwide, accounting for the third place of cancer incidence.Chronic inflammation, as seen in Crohn's disease and ulcerative colitis, is the most important risk factor for developing CRC, as it favours neoplastic transformation by enhancing epithelial cell turnover in the colonic mucosa.Treatments for CRC need to be improved; currently they are not specific and have several secondary effects in patients.The main objective of this work was to evaluate a new therapeutic strategy against a colitis-related colorectal cancer in vivo and in vitro by targeting mTOR-signaling and lactate dehydrogenase A. Together, these mechanisms directly affect tumor energetics.In this study we evaluated a better and more efficient triple therapy against a chronic inflammation-associated CRC in vivo and in vitro.After the development of tumors, mice were treated intraperitoneally during a forty-day period with single drugs or different combinations of Metformin, Sodium Oxamate and Doxorubicin.Targeted inhibition of the mTOR pathway, lactate dehydrogenase A and the concurrent use of Doxorubicin (called in this work as triple therapy), leaded to a notable reduction in the number and size of tumors in mice, and, a significant pro-inflammatory cytokines reduction Besides, we showed that treated cells were induced to early autophagy, and apoptosis cell death.Our results represent a novel and robust therapeutic strategy for overcoming CRC by means of targeting central molecular pathways in cancer by the combination of Metformin, Oxamate, and Doxorubicin leading to a rapid tumor growth inhibition and a dramatic colorectal crypt restoration.Besides, drug combination resulted in a notable reduction of anti-inflammatory cytokines.

Targeted Therapy

10.7150/jca.13123

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The Role of Glucocorticoids in Breast Cancer Therapy

Current Oncology (2022)

Irma B. Mitre-Aguilar Daniel Moreno-Mitre Jorge Meléndez-Zajgla Vilma Maldonado Nadia Jacobo‐Herrera

Glucocorticoids (GCs) are anti-inflammatory and immunosuppressive steroid molecules secreted by the adrenal gland and regulated by the hypothalamic–pituitary–adrenal (HPA) axis. GCs present a circadian release pattern under normal conditions; they increase their release under stress conditions. Their mechanism of action can be via the receptor-independent or receptor-dependent pathway. The receptor-dependent pathway translocates to the nucleus, where the ligand-receptor complex binds to specific sequences in the DNA to modulate the transcription of specific genes. The glucocorticoid receptor (GR) and its endogenous ligand cortisol (CORT) in humans, and corticosterone in rodents or its exogenous ligand, dexamethasone (DEX), have been extensively studied in breast cancer. Its clinical utility in oncology has mainly focused on using DEX as an antiemetic to prevent chemotherapy-induced nausea and vomiting. In this review, we compile the results reported in the literature in recent years, highlighting current trends and unresolved controversies in this field. Specifically, in breast cancer, GR is considered a marker of poor prognosis, and a therapeutic target for the triple-negative breast cancer (TNBC) subtype, and efforts are being made to develop better GR antagonists with fewer side effects. It is necessary to know the type of breast cancer to differentiate the treatment for estrogen receptor (ER)-positive, ER-negative, and TNBC, to implement therapies that include the use of GCs.

Progesterone receptor

Triple-negative breast cancer

10.3390/curroncol30010024

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Masticadienonic and 3α-OH Masticadienoic Acids Induce Apoptosis and Inhibit Cell Proliferation and Tumor Growth in Prostate Cancer Xenografts in Vivo

Molecules (2017)

Ma. Beatriz Sánchez-Monroy Nadia Jacobo‐Herrera Alejandro Zentella‐Dehesa Beatriz Hernández‐Téllez Mariano Martínez‐Vázquez

The triterpenes have been constituted as a group of interesting molecules as possible antitumor agents. Despite several of them not presenting a potent cytotoxic activity in vitro against cancer cells, in vivo in xenotransplant tumors studies, they show promising results. Based on the above considerations, we investigated the antitumor activity of both masticadienonic (MDA) and 3α-OH masticadienoic (3α-OH MDA) acids in a mouse prostate cancer xenograft model. Immunohistochemical assays were used to evaluate the decrease in the expression of the Proliferating Cell Nuclear Antigen (PCNA) and the Ki-67 induced by MDA and 3α-OH MDA. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to demonstrate the fragmentation of DNA. Our results showed that the two triterpenes inhibited tumor growth, had anti-proliferative effect in vivo and induced cell death by apoptosis. Collectively, our data suggested that the antitumor mechanism of MDA and 3α-OH MDA involves several molecular targets related to cell proliferation and apoptosis.

Fragmentation

Terminal deoxynucleotidyl transferase

10.3390/molecules22091479

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PAX8 is transcribed aberrantly in cervical tumors and derived cell lines due to complex gene rearrangements

International Journal of Oncology (2016)

Eduardo López–Urrutia Abraham Pedroza‐Torres Jorge Fernández‐Retana David Cantú de León Fermín Morales-González

The transcription factor PAX8, a member of the paired box-containing gene family with an important role in embryogenesis of the kidney, thyroid gland and nervous system, has been described as a biomarker in tumors of the thyroid, parathyroid, kidney and thymus. The PAX8 gene gives rise to four isoforms, through alternative mRNA splicing, but the splicing pattern in tumors is not yet established. Cervical cancer has a positive expression of PAX8; however, there is no available data determining which PAX8 isoform or isoforms are present in cervical cancer tissues as well as in cervical carcinoma-derived cell lines. Instead of a differential pattern of splicing isoforms, we found numerous previously unreported PAX8 aberrant transcripts ranging from 378 to 542 bases and present in both cervical carcinoma-derived cell lines and tumor samples. This is the first report of PAX8 aberrant transcript production in cervical cancer. Reported PAX8 isoforms possess differential transactivation properties; therefore, besides being a helpful marker for detection of cancer, PAX8 isoforms can plausibly exert differential regulation properties during carcinogenesis.

PAX8

10.3892/ijo.2016.3515

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Transcript Profiling Distinguishes Complete Treatment Responders With Locally Advanced

Jorge Fernández‐Retana Federico Lasa-Gonsebatt Eduardo López–Urrutia Jaime Coronel-Martínez David Cantú de León

Cervical cancer (CC) mortality is a major public health concern since it is the second cause of cancer-related deaths among women. Patients diagnosed with locally advanced CC (LACC) have an important rate of recurrence and treatment failure.ConventionaltreatmentforLACCisbasedonchemotherapyandradiotherapy;however,upto40%ofpatientswill not respond to conventional treatment; hence, we searched for a prognostic gene signature able to discriminate patients who do not respond to the conventional treatment employed to treat LACC. Tumor biopsies were profiled with genomewide high-density expression microarrays. Class prediction was performed in tumor tissues and the resultant gene signaturewas validated by quantitative reversetranscription–polymerasechain reaction. A27-predictivegeneprofilewas identified through its association with pathologic response. The 27-gene profile was validated in an independent set of

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Laherradurin Inhibits Colorectal Cancer Cell Growth by Induction of Mitochondrial Dysfunction and Autophagy Induction

Cells (2024)

Izamary Delgado-Waldo Svetlana Dokudovskaya Yahir A. Loissell-Baltazar Eduardo Pérez-Arteaga Jossimar Coronel-Hernández

LAH, an acetogenin from the Annonaceae family, has demonstrated antitumor activity in several cancer cell lines and in vivo models, where it reduced the tumor size and induced programmed cell death. We focused on the effects of LAH on mitochondrial dynamics, mTOR signaling, autophagy, and apoptosis in colorectal cancer (CRC) cells to explore its anticancer potential. Methods: CRC cells were treated with LAH, and its effects on mitochondrial respiration and glycolysis were measured using Seahorse XF technology. The changes in mitochondrial dynamics were observed through fluorescent imaging, while Western blot analysis was used to examine key autophagy and apoptosis markers. Results: LAH significantly inhibited mitochondrial complex I activity, inducing ATP depletion and a compensatory increase in glycolysis. This disruption caused mitochondrial fragmentation, a trigger for autophagy, as shown by increased LC3-II expression and mTOR suppression. Apoptosis was also confirmed through the cleavage of caspase-3, contributing to reduced cancer cell viability. Conclusions: LAH’s anticancer effects in CRC cells are driven by its disruption of mitochondrial function, triggering both autophagy and apoptosis. These findings highlight its potential as a therapeutic compound for further exploration in cancer treatment.

Fragmentation

10.3390/cells13191649

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Chemical Composition of Mexicali Propolis and Its Effect on Gastric Repair in an Indomethacin-Induced Gastric Injury Murine Model

Antioxidants (2025)

Pilar Domínguez-Verano Nadia Jacobo‐Herrera Andrés Castell-Rodrı́guez Octavio Canales-Álvarez María Margarita Canales-Martinez

Propolis is a resinous substance produced by bees that has several biomedical properties that could contribute to the repair process of the gastric mucosa, such as antioxidant, anti-inflammatory, healing, and gastroprotective properties. Thus, this study aimed to determine the chemical composition of Mexicali propolis, its antioxidant capacity, and its effect on gastric repair. Three polarity-directed extracts were obtained: the ethanolic extract, the ethyl acetate extract, and the hexane extract. The antioxidant activity, total phenolic content (TPC), and flavone/flavonol content were determined for each extract. The chemical composition was analysed using HPLC-TOF-MS (High-Performance Liquid Chromatography-Time-Of-Flight Mass Spectrometry) and GC-MS (Gas Chromatography-Mass Spectrometry), and a total of 52 compounds were identified. The results revealed that the ethanolic extract had the greatest effect on free radical scavenging and the content of bioactive compounds. On the basis of these results, the effect of the Mexicali ethanolic extract of propolis (MeEEP) on gastric repair was subsequently evaluated. Prior to the evaluation, MeEEP was found to exhibit low oral toxicity, as determined under the Organisation for Economic Co-operation and Development (OECD) 425 guidelines. Gastric injury was induced in male C57BL/6 mice by intragastric administration of indomethacin (10 mg/kg). MeEEP (300 mg/kg) was administered 6 h after the induction of injury using indomethacin and daily thereafter. The mice were sacrificed at 12, 24, and 48 h to assess the effect. As a result, MeEEP enhanced the repair of the gastric lesion by decreasing the percentage of the bleeding area and attenuating the severity of histological damage, as demonstrated by H&E staining. This effect was associated with a reduction in MPO enzyme activity and in the levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6, maintaining controlled inflammation in gastric tissue. Furthermore, the administration of the extract increased SOD enzymatic activity and GSH levels, reducing the degree of oxidative damage in the gastric tissue, as demonstrated by low MDA levels. Finally, after evaluating the effect on apoptosis via immunohistochemistry, MeEEP was shown to reduce the expression of the proapoptotic marker Bax and increase the expression of the antiapoptotic marker Bcl-2. In conclusion, these findings suggest that MeEEP may enhance gastric repair through a cytoprotective mechanism by controlling inflammation exacerbation, reducing oxidative stress, and regulating apoptosis. These mechanisms are primarily attributed to the presence of pinocembrin, tectochrysin, chrysin, apigenin, naringenin, acacetin, genistein, and kaempferol. It is important to highlight that this study provides a preliminary exploration of the reparative effect of Mexican propolis, describing the potential mechanisms of action of the compounds present in Mexicali propolis.

Propolis

10.3390/antiox14010065

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Gene Promoter-Methylation Signature as Biomarker to Predict Cisplatin-Radiotherapy Sensitivity in Locally Advanced Cervical Cancer

Frontiers in Oncology (2022)

Carlos Contreras-Romero Eloy-Andrés Pérez-Yépez Antonio Daniel Martínez-Gutiérrez Alma D. Campos-Parra Alejandro Zentella‐Dehesa

Despite efforts to promote health policies focused on screening and early detection, cervical cancer continues to be one of the leading causes of mortality in women; in 2020, estimated 30,000 deaths in Latin America were reported for this type of tumor. While the therapies used to treat cervical cancer have excellent results in tumors identified in early stages, those women who are diagnosed in locally advanced and advanced stages show survival rates at 5 years of <50%. Molecular patterns associated with clinical response have been studied in patients who present resistance to treatment; none of them have reached clinical practice. It is therefore necessary to continue analyzing molecular patterns that allow us to identify patients at risk of developing resistance to conventional therapy. In this study, we analyzed the global methylation profile of 22 patients diagnosed with locally advanced cervical cancer and validated the genomic results in an independent cohort of 70 patients. We showed that BRD9 promoter region methylation and CTU1 demethylation were associated with a higher overall survival (p = 0.06) and progression-free survival (p = 0.0001), whereas DOCK8 demethylation was associated with therapy-resistant patients and a lower overall survival and progression-free survival (p = 0.025 and p = 0.0001, respectively). Our results suggest that methylation of promoter regions in specific genes may provide molecular markers associated with response to treatment in cancer; further investigation is needed.

10.3389/fonc.2022.773438

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Reversal of Multidrug Resistance by Morning Glory Resin Glycosides in Human Breast Cancer Cells

Journal of Natural Products (2011)

Gabriela Figueroa‐González Nadia Jacobo‐Herrera Alejandro Zentella‐Dehesa Rogelio Pereda‐Miranda

Reversal of multidrug resistance (MDR) by thirty resin glycosides from the morning glory family (Convolvulaceae) was evaluated in vinblastine-resistant human breast carcinoma cells (MCF-7/Vin). The effects of these amphipathic compounds on the cytotoxicity and P-glycoprotein (P-gp)-mediated MDR were estimated with the sulforhodamine B colorimetric assay. Active noncytotoxic compounds exerted a potentiation effect of vinblastine susceptibility by 1- to over 1906-fold at tested concentrations of 5 and 25 μg/mL. Murucoidin V (1) enhanced vinblastine activity 255-fold when incorporated at 25 μg/mL and also, based on flow cytometry, significantly increased the intracellular accumulation of rhodamine 123 with the use of reserpine as a positive control for a MDR reversal agent. Incubation of MCF-7/Vin cells with 1 caused an increase in uptake and notably lowered the efflux rate of rhodamine 123. Decreased expression of P-glycoprotein by compound 1 was detected by immunofluorescence flow cytometry after incubation with an anti-P-gp monoclonal antibody. These results suggest that resin glycosides represent potential efflux pump inhibitors for overcoming MDR in cancer therapy.

Rhodamine 123

Efflux

P-glycoprotein

Sulforhodamine B

10.1021/np200864m

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Citations (86)