Master degree in Biological Sciences: Biochemistry
19
Scopus Publications
Scopus Publications
Targeting Prostate Cancer Metabolism Through Transcriptional and Epigenetic Modulation: A Multi-Target Approach to Therapeutic Innovation Pedro Juan Espitia-Pérez, Lyda Marcela Espitia-Perez, Mario Negrette-Guzmán International Journal of Molecular Sciences, 2025 Prostate cancer (PCa) therapy faces challenges due to tumor heterogeneity, plasticity, and progression. Metabolic reprogramming, a dynamic process, has emerged as a key focus in PCa treatment. However, conventional therapies targeting cancer-specific metabolic pathways or employing chemosensitizers are often limited by compensatory mechanisms and metabolic complexity. This review highlights the roles of transcription factors, including AR, p53, c-Myc, HIF-1, Nrf2, and PPARγ, in regulating PCa metabolism by influencing signaling pathways, enzymes, and gene expression. Multi-target compounds, particularly natural products, show potential for disrupting multiple metabolic enzymes, opening up new research possibilities. Notable examples include β-elemene, juglone, tannic acid, and withaferin A, which target critical metabolic processes through enzyme inhibition, transcription factor modulation, epigenetic changes, and protein interaction disruption. Naturally derived metabolites can elicit transversal responses in diverse metabolic pathways, particularly in p53 and MYC transcription factors. Additionally, compounds such as pentacyclic terpenoids (ursolic acid with ursane skeleton), sulforaphane, and isothiocyanate-related moieties may induce metabolic and epigenetic changes through S-adenosyl methionine (SAM) and acetyl-CoA modulation, potentially affecting new areas of research through metabolic processes. We propose a cooperative crosstalk between metabolic reprogramming and transcription factors/epigenetic modulation in PCa. This approach holds potential for expanding PCa therapeutics and opening new avenues for research.
Genetic Damage and Multi-Elemental Exposure in Populations in Proximity to Artisanal and Small-Scale Gold (ASGM) Mining Areas in North Colombia Pedro Espitia-Pérez, Lyda Espitia-Pérez, Ana Peñata-Taborda, Hugo Brango, Karina Pastor-Sierra, et al. Toxics, 2025 This study evaluates DNA damage and multi-element exposure in populations from La Mojana, a region of North Colombia heavily impacted by artisanal and small-scale gold mining (ASGM). DNA damage markers from the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay, including micronucleated binucleated cells (MNBN), nuclear buds (NBUDs) and nucleoplasmic bridges (NPB), were assessed in 71 exposed individuals and 37 unexposed participants. Exposed individuals had significantly higher MNBN frequencies (PR = 1.26, 95% CI: 1.02–1.57, p = 0.039). Principal Component Analysis (PCA) identified the “Soil-Derived Mining-Associated Elements” (PC1), including V, Fe, Al, Co, Ba, Se and Mn, as being strongly associated with high MNBN frequencies in the exposed population (PR = 10.45, 95% CI: 9.75–12.18, p < 0.001). GAMLSS modeling revealed non-linear effects of PC1, with greater increases in MNBN at higher concentrations, especially in exposed individuals. These results highlight the dual role of essential and toxic elements, with low concentrations being potentially protective but higher concentrations increasing genotoxicity. Women consistently exhibited higher MNBN frequencies than men, suggesting sex-specific susceptibilities. This study highlights the compounded risks of chronic metal exposure in mining-impacted regions and underscores the urgent need for targeted interventions to mitigate genotoxic risks in vulnerable populations.
Combination of Low-Dose Sulforaphane and Docetaxel on Mitochondrial Function and Metabolic Reprogramming in Prostate Cancer Cell Lines Ana Peñata-Taborda, Pedro Espitia-Pérez, Lyda Espitia-Pérez, Andrés Coneo-Pretelt, Hugo Brango, et al. International Journal of Molecular Sciences, 2025 Considering the limitations of monotherapies due to chemoresistance and side effects, this research aimed to determine whether low doses of sulforaphane (SFN) combined with docetaxel (DCT) could enhance therapeutic efficacy. Prostate cancer cell lines LNCaP and PC-3 were treated with individual IC50 doses of SFN and DCT and half-reduced IC50 values for the SFN:DCT combination. Metabolic markers, including glucose consumption, lactate production, reactive oxygen species (ROS), mitochondrial mass, and caspase activity, were assessed. In LNCaP cells, the SFN:DCT combination reduced cell viability to 50%, comparable to DCT monotherapy (48%). Caspase 3 activation was also higher with SFN:DCT (2.4 ± 0.75 RFU) than DCT alone (2.1 ± 0.47 RFU), while caspase 8 activation remained comparable, indicating equivalent effectiveness at lower concentrations. In PC-3 cells, the combination induced caspase 3 activation (1.16 ± 0.0484 RFU) at levels slightly lower than DCT (1.51 ± 0.2062 RFU) but achieved greater reductions in mitochondrial mass, reflecting its ability to target metabolic vulnerabilities in aggressive phenotypes. Our findings suggest that the SFN:DCT combination is a promising strategy for early-stage prostate cancer. By achieving comparable efficacy to DCT monotherapy at low doses, the SFN:DCT combination maintains the therapeutic impact, mitigating the adverse effects of conventional DCT treatment.
Genotoxicity and Cytotoxicity Induced In Vitro by Airborne Particulate Matter (PM2.5) from an Open-Cast Coal Mining Area Claudia Galeano-Páez, Hugo Brango, Karina Pastor-Sierra, Andrés Coneo-Pretelt, Gean Arteaga-Arroyo, et al. Atmosphere, 2024 This study evaluates the cytotoxic and genotoxic effects of PM2.5 collected from an open-cast coal mining area in northern Colombia. Cyclohexane (CH), dichloromethane (DCM), and acetone (ACE) extracts were obtained using Soxhlet extraction to isolate compounds of different polarities. Human lymphocytes were exposed to the extracted compounds, and cytotoxicity and genotoxicity were assessed using the cytokinesis block micronucleus (CBMN) and comet assays, incorporating FPG and ENDO III enzymes to detect oxidative DNA damage. Chemical analysis revealed that the organic fractions consisted mainly of modified hydrocarbons and volatile organic compounds. The CBMN assay showed a significant increase in micronuclei in binucleated (MNBN) and mononucleated (MNMONO) cells and nucleoplasmic bridges (NPB) in exposed lymphocytes. The comet assay revealed substantial oxidative DNA damage, particularly with the ACE extract, which significantly increased oxidized purines and pyrimidines. DCM induced similar effects, while CH showed moderate effects. CREST immunostaining revealed aneugenic activity, particularly in cells exposed to ACE and DCM extracts. These results suggest that polar fractions of PM2.5, likely containing metals and modified PAHs, contribute to DNA damage and chromosomal instability. The study highlights the need to monitor the composition of PM2.5 in mining regions to implement stricter environmental policies to reduce exposure and health risks.
Micronuclei, Pesticides, and Element Mixtures in Mining Contexts: The Hormetic Effect of Selenium Marcela E. Varona-Uribe, Sonia M. Díaz, Ruth-Marien Palma, Leonardo Briceño-Ayala, Carlos Trillos-Peña, et al. Toxics, 2023 The contexts where there are mining and agriculture activities are potential sources of risk to human health due to contamination by chemical mixtures. These contexts are frequent in several Colombian regions. This study explored the potential association between the frequency of micronuclei and pesticides and elements in regions with ferronickel (Montelibano, Córdoba) and gold (Nechí, Antioquia) mining, and a closed native mercury mine (Aranzazu, Caldas), with an emphasis in the potential effect of selenium as a potential chelator. A cross-sectional study was carried out with 247 individuals. Sociodemographic, occupational, and toxicological variables were ascertained. Blood and urine samples were taken for pesticide analysis (5 organophosphates, 4 organochlorines, and 3 carbamates), 68 elements were quantified in hair, and micronuclei were quantified in lymphocytes. The mixtures of elements were grouped through principal component analysis. Prevalence ratios were estimated with robust variance Poisson regressions to explore associations. Interactions of selenium with toxic elements were explored. The highest concentrations of elements were in the active mines. The potentially most toxic chemical mixture was observed in the ferronickel mine. Pesticides were detected in a low proportion of participants (<2.5%), except paraoxon-methyl in blood (27.55%) in Montelibano and paraoxon-ethyl in blood (18.81%) in Aranzazu. The frequency of micronuclei was similar in the three mining contexts, with means between 4 to 7 (p = 0.1298). There was great heterogeneity in the exposure to pesticides and elements. The “hormetic effect” of selenium was described, in which, at low doses, it acts as a chelator in Montelibano and Aranzazu, and at high doses, it can enhance the toxic effects of other elements, maybe as in Nechí. Selenium can serve as a protective agent, but it requires adaptation to the available concentrations in each region to avoid its toxic effects.
Genetic Instability among Hitnü People Living in Colombian Crude-Oil Exploitation Areas Claudia Galeano-Páez, Dina Ricardo-Caldera, Luisa Jiménez-Vidal, Ana Peñata-Taborda, Andrés Coneo-Pretelt, et al. International Journal of Environmental Research and Public Health, 2022 Oil exploitation, drilling, transportation, and processing in refineries produces a complex mixture of chemical compounds, including polycyclic aromatic hydrocarbons (PAHs), which may affect the health of populations living in the zone of influence of mining activities (PZOI). Thus, to better understand the effects of oil exploitation activities on cytogenetic endpoint frequency, we conducted a biomonitoring study in the Hitnü indigenous populations from eastern Colombia by using the cytokinesis micronucleus cytome assay (CBMN-cyt). PAH exposure was also measured by determine urine 1-hydroxypyrene (1-OHP) using HPLC. We also evaluated the relationship between DNA damage and 1-OHP levels in the oil exploitation area, as well as the modulating effects of community health factors, such as Chagas infection; nutritional status; and consumption of traditional hallucinogens, tobacco, and wine from traditional palms. The frequencies of the CBMN-cyt assay parameters were comparable between PZOI and Hitnü populations outside the zone of influence of mining activities (POZOI); however, a non-significant incremental trend among individuals from the PZOI for most of the DNA damage parameters was also observed. In agreement with these observations, levels of 1-OHP were also identified as a risk factor for increased MN frequency (PR = 1.20) compared to POZOI (PR = 0.7). Proximity to oil exploitation areas also constituted a risk factor for elevated frequencies of nucleoplasmic bridges (NPBs) and APOP-type cell death. Our results suggest that genetic instability and its potential effects among Hitnü individuals from PZOI and POZOI could be modulated by the combination of multiple factors, including the levels of 1-OHP in urine, malnutrition, and some traditional consumption practices.
