Effects of Fucoidan and Chemotherapeutic Agent Combinations on Malignant and Non-malignant Breast Cell Lines.
Curr Pharm Biotechnol
; 18(9): 748-757, 2017.
Article
em En
| MEDLINE
| ID: mdl-29141543
ABSTRACT
OBJECTIVES:
Breast cancer is a leading cause of death among women in both developed and Third World countries. Fucoidan is a natural plant metabolite produced by brown seaweeds with proven anticancer potential. This study determined the cytotoxic, apoptotic and cell cycle effects of fucoidan alone and in combination with first-line anticancer drugs (cisplatin, doxorubicin and taxol) in MCF-7 breast cancer cells and non-malignant MCF-12A breast epithelial cells as control.METHODS:
Cytotoxicity was evaluated using the MTT reduction assay. Cell cycle distribution and apoptosis were assessed by flow cytometry using Annexin VFITC/PI and Hoechst 33342 staining, and caspases-3, -7 and -9 activation.RESULTS:
Fucoidan alone was significantly more cytotoxic to MCF-7 breast cancer cells compared to the MCF-12A non-cancerous breast epithelial cell line. In MCF-7 cells, the presence of fucoidan caused cell cycle arrest at G1 with accumulation of cells in the sub-G1 phase with the activation of caspases-3,-7 and -9. Furthermore, combination of fucoidan with the standard chemotherapeutic agents-cisplatin, doxorubicin and taxol-significantly enhanced the cytotoxicity of these drugs and accumulation of cells in the G2/M and sub-G1 phases, and induction of apoptosis. No significant differences were observed between fucoidan-treated and untreated MCF-12A cells with respect to cytotoxicity and cell cycle distribution profiles. By contrast, in non-cancerous MCF-12A cells, fucoidan attenuated the toxicity of doxorubicin and cisplatin in combination by increasing their IC50 values. This effect was not demonstrated with the taxol combination.CONCLUSIONS:
Fucoidan is an effective antitumor agent, either alone or in combination with cisplatin, doxorubicin and taxol in MCF-7 breast cancer cells. Drug combinations that discriminate between cancerous and non-cancerous cells afford a plausible and viable strategy of attaining therapeutic efficacy and avoiding possible toxicity and side effects. These findings suggest that fucoidan is a promising candidate for cancer combination therapies.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Polissacarídeos
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Apoptose
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Células Epiteliais
Limite:
Female
/
Humans
Idioma:
En
Revista:
Curr Pharm Biotechnol
Ano de publicação:
2017
Tipo de documento:
Article