Category Archives: Cytotoxicity

Genotoxicity in occupational exposure to antineoplastic drugs

J Pharm Pharmacogn Res 4(3): 122-133, 2016.

Original Article | Artículo Original

Genotoxicity biomarkers for monitoring occupational exposure to antineoplastic drugs

[Biomarcadores de genotoxicidad para el monitoreo de la exposición ocupacional a fármacos antineoplásicos]

Hilda M. Rodríguez-Montero1, Esther Argote-Pelegrino2, Adriana Díaz-Curbelo3, Elizabeth B. Cuétara-Lugo1*

1Institute of Oncology and Radiobiology of Cuba. 29 y F, Vedado CP 10400. La Habana. Cuba.
2Cuban Society of Veterinary. Paseo e/ 23 y 25, Vedado CP 10400. La Habana. Cuba
3Centro of Applied Technologies and Nuclear Development. 30 y 5ta Avenida. Miramar. Playa. La Habana. Cuba.
Abstract

Context: The Institute of Oncology and Radiobiology (INOR) is the leading institution for the diagnosis, treatment and follow-up of cancer in Cuba. The main methods used in cancer treatment are surgery, radiotherapy and chemotherapy. The last one involves the handling of hazardous substances, such as cytostatics, which implies a health risk to persons occupationally exposed to it. There are two sites where a considerable among of cytostatic is handled (Ambulatory Chemotherapy Room (ACR) and the Central Unit of Cytostatic Mixture Preparation (CUCM)). Genotoxicity biomarkers of exposure and effects have been widely used to detect occupational environment hazards.

Aims: To evaluate genotoxicity biomarkers indicative of exposure and effects to cytostatics.

Methods: In this study were tested samples taken from the surfaces of biological safety cabinets located in the Central Unit of Cytostatic Mixture using SOS – Chromotest. We also evaluated samples of oral mucosa exfoliated cells from exposed and control subjects, by micronucleus test.

Results: All subjects were exposed and subjects who administered the mixes in the institution had an increased of DNA damage in comparison with the pharmaceutical staff that prepared it and wear the primary protection barriers properly.

Conclusions: These results underline the efficiency of genotoxicological biomarkers in detecting the exposure levels and the deleterious effect of cytostatics on occupationally exposed personal.

Keywords: Biosafety; cytostatic handling; micronucleus test; occupational health; SOS Chromotest.

Resumen

Contexto: El Instituto de Oncología y Radiobiología (INOR) es la institución líder en el diagnóstico, tratamiento y seguimiento del cáncer en Cuba. Los principales métodos usados en el tratamiento son: la cirugía, la radio y quimioterapias. Esta última involucra el manejo de sustancias peligrosas, como los son los citostáticos que implican un riesgo a la salud de las personas que lo manipulan. Existen dos sitios donde se manipulan grandes volúmenes de estas sustancias la Sala de Quimioterapia Ambulatoria (ACR) y la Unidad Central de Mezclas Citostáticas (CUMC). Los marcadores de genotoxicidad han sido ampliamente empleados para detectar peligros en el ambiente laboral.

Objetivos: Evaluar biomarcadores de genotoxicidad indicativos de exposición y efecto a citostáticos.

Métodos: Las investigaciones farmacognósticas y fitoquímicas se llevaron a cabo en relación con los parámetros macroscópicos, microscópicos y fitoquímicos preliminares.

Resultados: Se evaluaron muestras tomadas de las superficies de las cabinas de seguridad biológica de la CUCM usando el SOS – Chromotest. También se evaluaron muestras de células exfoliadas de la mucosa bucal de sujetos expuestos y controles mediante el ensayo de micronúcleos.

Conclusiones: Estos resultados ponen de manifiesto la eficacia de los biomarcadores genotoxicológicos en la detección de los niveles de exposición y el efecto nocivo de los citostáticos en el personal expuesto ocupacionalmente.

Palabras Clave: Bioseguridad; ensayo SOS; manejo de citostáticos; prueba de micronúcleos; salud ocupacional.

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Citation Format: Hilda M. Rodríguez-Montero, Esther Argote-Pelegrino, Adriana Díaz-Curbelo, Elizabeth B. Cuétara-Lugo (2016) Genotoxicity biomarkers for monitoring occupational exposure to antineoplastic drugs. J Pharm Pharmacogn Res 4(3): 122-133.
This article has been cited by:
Rodríguez Montero HM, Reyes Reyes E, Escalante Leyva T, Correa Águila R, Torres Valle A, Cuétara-Lugo EB (2018) Monitoreo de seguridad ocupacional en el manejo de citostáticos [Biosafety of citostatic drug handling]. J Pharm Pharmacogn Res 6(6): 433–447. Website

© 2016 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Cytotoxicity of 1-O-undecylglycerol in melanoma

J Pharm Pharmacogn Res 4(2): 84-94, 2016.

Original Article | Artículo Original

Selective cytotoxic effect of 1-O-undecylglycerol in human melanoma cells

[Efecto citotóxico selectivo del 1-O-undecilglicerol en células de melanoma humano]

Marian Hernández-Colina1*, Alberto Martín Cermeño1, Alexis Díaz García2

1Instituto de Farmacia y Alimentos, Universidad de la Habana, Calle 222, No. 2317, entre 23 y 31, La Coronela, La Lisa, CP 13600, La Habana, Cuba.
2Laboratorios de Producciones Biofarmacéuticas y Químicas (LABIOFAM). Ave. Boyeros Km 16½, Rpto. Mulgoba, Boyeros, La Habana, Cuba.
Abstract

Context: 1-O-alkylglycerols are ether-linked glycerols derived from shark liver oil and found in small amounts in human milk. Previous studies showed antineoplastic activity for this family of compounds, structurally related to alkylphospholipids, but the activity of linear chain synthetic alkylglycerols in cancer cell lines is less documented. Melanoma is a high incidence cancer, highly resistant to potential treatments. Finding new anti-cancer compounds to improve melanoma prognosis is a relevant research issue.

Aims: To study the cytotoxic effect of 1-O-undecylglycerol in primary cultured normal fibroblasts and A375 human melanoma cell line.

Methods: Cells were treated with different concentrations of 1-O-undecylglycerol and viability assessed by MTT assay. Morphological changes were visualized by DAPI and acridine orange-ethidium bromide staining. Mitochondrial membrane potential was evaluated, and gene expression of P53 and BcL-2 was semi-quantified.

Results: 1-O-undecylglycerol decreased viability of A375 cells and exerted very low cytotoxicity on primary cultured normal fibroblasts. Necrosis appeared in A375 cells but not in fibroblasts, and no apoptotic changes were visualized in DAPI staining experiments. After 24 h fibroblasts and melanoma cells developed mitochondrial potential changes similar to valinomycin. The gene expression of P53 and BcL-2 decreased in treated cells.

Conclusions: 1-O-undecylglycerol exhibited selective cytotoxic activity in A375 melanoma cells when compared with primary cultured fibroblast. Its toxicity is mediated by necrosis that may be related with mitochondrial events and decrease in P53 and BcL-2 expression. The results suggest that UDG could be a useful strategy to combine with other chemotherapeutic agents in melanoma treatment.

Keywords: Alkylglycerols, cytotoxicity, melanoma, primary cultured fibroblasts.

Resumen

Contexto: Los 1-O-alquilgliceroles son éteres presentes en el aceite de hígado de tiburón y en la leche materna. Han mostrado actividad antineoplásica, pero está poco documentada para alquilgliceroles sintéticos de cadena lineal. La búsqueda de nuevos antitumorales para mejorar el pronóstico del melanoma resulta relevante, debido a su alta incidencia y resistencia.

Objetivos: Estudiar el efecto citotóxico del 1-O-undecilglicerol en cultivo primario de fibroblastos normales y la línea celular A375 de melanoma humano.

Métodos: En células tratadas con diferentes concentraciones de 1-O-undecilglicerol se monitoreó la viabilidad mediante ensayo con MTT. Los cambios morfológicos se visualizaron por tinción con DAPI y naranja acridina- bromuro de etidio. Se evaluó el potencial de membrana mitocondrial, y se semi-cuantificó la expresión de los genes P53 y BcL-2.

Resultados: El 1-O-undecilglicerol redujo la viabilidad de las células A375, y ejerció poca citotoxicidad en el cultivo primario de fibroblastos normales. Ocurrió necrosis en las células A375 pero no en los fibroblastos, y no se visualizaron cambios apoptóticos en la tinción con DAPI. Luego de 24 h ambas células desarrollaron cambios en el potencial de membrana mitocondrial similar a la valinomicina, y disminuyó la expresión de los genes p53 y BcL-2.

Conclusiones: El 1-O-undecilglicerol mostró actividad citotóxica selectiva en células A375 al compararlo con cultivo primario de fibroblastos humanos. Su toxicidad es mediada por necrosis, probablemente por eventos mitocondriales y disminución en la expresión de P53 y BcL-2. Ello sugiere que el 1-O-undecilglicerol pudiera ser útil en combinación con otros quimioterapéuticos en el tratamiento del melanoma.

Palabras Clave: Alquilgliceroles, citotoxicidad, cultivo primario de fibroblastos melanoma, necrosis.

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Citation Format: Marian Hernández-Colina, Alberto Martín Cermeño, Alexis Díaz García (2016) Selective cytotoxic effect of 1-O-undecylglycerol in human melanoma cells. J Pharm Pharmacogn Res 4(2): 84-94.

© 2016 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

C 045: SELECTIVE CYTOTOXIC ACTIVITY OF 1-O-UNDECYL GLYCEROL

J Pharm Pharmacogn Res 2(Suppl. 1): S123, 2014

Special supplement with the abstract book of LATINFARMA 2013

Conference

C 045: SELECTIVE CYTOTOXIC ACTIVITY OF 1-O-UNDECYL GLYCEROL

Hernández-Colina M1, Martín A2, Calero A, Del Toro G.1

1Pharmacology &Toxicology Dept., Pharmacy and Food Institute. Havana, Cuba. E-mail: marianhc@ifal.uh.cu
2Center for Genetic Engineering and Biotechnology, Havana, Cuba.
Abstract

1-O-alkylglycerols exhibit several pharmacological properties, which include sperm motility improvement, antidrepanocitary, antiangiogenic and antitumor activity. The cytotoxic activity of this family of compounds has been reported previously by our workgroup, but it didn´t include the 11 carbon chain molecule, 1-O-undecylglycerol (C11). The aim of this work was to demonstrate the cytotoxic activity of several concentrations of C11 in tumor cell cultures of different histological origins (A549, A375, MCF-7, MDA MB231), and compare with normal cell cultures (Vero cells, human primary fibroblast, 3T3A31, 184B5). Cytotoxicity was measured by MTT assay, and GI50 was determined using curve interpolation in GraphPad Prism v5.0. Taking into account the lowest GI50, obtained in breast cancer cells (MCF-7, MDAMB231), impedance measured by Real Time Cell Analyzer X-Celligence® performance showed differential behavior and cell index for cancer and normal breast cells treated with C11. The levels of caspase-3 and Akt after 3 and 24h of treatment with C11 changed in MCF-7 cells with respect to normal cells. We concluded that C11 has selective and concentration dependent cytotoxic action on cancer cell culture, which is more prominent in breast cancer cells, and mediated by apoptotic activity and Akt modulation in MCF-7 cells. 1-Oundecylglycerol could be a good candidate for further studies in selective anticancer therapy.