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Invest New Drugs. 2019 Jun 8. doi: 10.1007/s10637-019-00789-1. [Epub ahead of print]

Novel thiosemicarbazones induce high toxicity in estrogen-receptor-positive breast cancer cells (MCF7) and exacerbate cisplatin effectiveness in triple-negative breast (MDA-MB231) and lung adenocarcinoma (A549) cells.

Author information

1
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Col. Los Reyes Iztacala, CP 54059, Tlalnepantla, Estado de México, Mexico.
2
Facultad de Ciencias Químicas, Universidad Autónoma Benito Juárez, Oaxaca, Mexico.
3
Laboratorio Nacional en Salud: Diagnóstico Molecular y Efecto Ambiental en Enfermedades Crónico-Degenerativas, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Col. Los Reyes Iztacala, CP 54059, Tlalnepantla, Estado de México, Mexico.
4
Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, México.
5
Carrera de Enfermería, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Col. Los Reyes Iztacala, CP 54059, Tlalnepantla, Estado de México, Mexico.
6
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Col. Los Reyes Iztacala, CP 54059, Tlalnepantla, Estado de México, Mexico. felipe.vaca@gmail.com.
7
Laboratorio Nacional en Salud: Diagnóstico Molecular y Efecto Ambiental en Enfermedades Crónico-Degenerativas, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Col. Los Reyes Iztacala, CP 54059, Tlalnepantla, Estado de México, Mexico. felipe.vaca@gmail.com.
8
Subdirección de Investigación Básica, Instituto Nacional de Cancerología, San Fernando No. 22, Tlalpan, CP 14080, Ciudad de México, Mexico. felipe.vaca@gmail.com.

Abstract

Cis-diamminedichloroplatinum(II) (CDDP), known as cisplatin, has been extensively used against breast cancer, which is the most frequent cancer among women, and lung cancer, the leading cancer that causes death worldwide. Novel compounds such as thiazole derivatives have exhibited antiproliferative activity, suggesting they could be useful against cancer treatment. Herein, we synthesized two novel thiosemicarbazones and an aldehyde to combine with CDDP to enhance efficacy against ER-positive breast MCF7 cancer cells, triple-negative/basal-B mammary carcinoma cells (MDA-MB231) and lung adenocarcinoma (A549) human cells. We synthesized 2,3,5,6-tetrafluoro-4-(2-mercaptoetanothiolyl)benzaldehyde (ALD), 5-[(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl)thio]-2-furaldehyde thiosemicarbazone (TSC1) and 5-[(4-(trifluoromethyl)phenyl)thio]-2-furaldehyde thiosemicarbazone (TSC2) and used them alone or in combination with subtoxic CDDP concentrations to evaluate cytotoxicity, cytoskeleton integrity and mitochondrial function. We found that none of the synthesized compounds improved CDDP activity against MCF7 cell cultures; however, TSC2 was effective in enhancing the cytotoxicity of CDDP against MDA-MB231 and A549 cancer cell cultures. We demonstrated that the cytotoxic effect is related to the TSC2 capacity to induce disruption in the cytoskeleton network and to decrease mitochondrial function.

KEYWORDS:

Breast cancer cells; Cytoskeleton disruption; Lung cancer cells; Mitochondrial dysfunction; Thiosemicarbazones

PMID:
31177399
DOI:
10.1007/s10637-019-00789-1

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