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Transcriptome analysis of genes associated with breast cancer cell motility in response to Artemisinin treatment.
Kumari, Kanchan; Keshari, Sunita; Sengupta, Debomita; Sabat, Surendra C; Mishra, Sandip K.
Afiliação
  • Kumari K; Cancer Biology Laboratory, Institute of Life Sciences (Government of India), Nalco Square, Bhubaneswar, Odisha, 751023, India.
  • Keshari S; National Central University, Chungli, Taiwan.
  • Sengupta D; Department of Molecular Medicine, Bose Institute, Kolkata, India.
  • Sabat SC; Molecular biology of abiotic stress, Institute of Life Sciences, Nalco Square, Bhubaneswar, Odisha, 751023, India.
  • Mishra SK; Cancer Biology Laboratory, Institute of Life Sciences (Government of India), Nalco Square, Bhubaneswar, Odisha, 751023, India. sandipkmishra@hotmail.com.
BMC Cancer ; 17(1): 858, 2017 Dec 15.
Article em En | MEDLINE | ID: mdl-29246124
ABSTRACT

BACKGROUND:

Well-known anti-malarial drug artemisinin exhibits potent anti-cancerous activities. In-vivo and in-vitro studies showed its anti-tumor and immunomodulatory properties signifying it as a potent drug candidate for study. The studies of mechanisms of cell movement are relevant which can be understood by knowing the involvement of genes in an effect of a drug. Although cytotoxicity and anti-proliferative activity of artemisinin is evident, the genes participating in its anti-migratory and reduced invasive effect are not well studied. The present study reports the alteration in the expression of 84 genes involved in cell motility upon artemisinin treatment in MCF-7 breast cancer cells using pathway focused gene expression PCR array. In addition, the effect of artemisinin on epigenetic modifier HDACs is studied.

METHODS:

We checked the functional stimulus of artemisinin on cell viability, migration, invasion and apoptosis in breast cancerous cell lines. Using qRT-PCR and western blot, we validated the altered expression of relevant genes associated with proliferation, migration, invasion, apoptosis and mammary gland development.

RESULTS:

Artemisinin inhibited cell proliferation of estrogen receptor negative breast cancer cells with fewer efficacies in comparison to estrogen receptor positive ones. At the same time, cell viability and proliferation of normal breast epithelial MCF10A cells was un-affected. Artemisinin strongly inhibited cancer cell migration and invasion. Along with orphan nuclear receptors (ERRα, ERRß and ERRγ), artemisinin altered the ERα/ERß/PR/Her expression status of MCF-7 cells. The expression of genes involved in the signaling pathways associated with proliferation, migration, invasion and apoptosis was significantly altered which cooperatively resulted into reduced growth promoting activities of breast cancer cells. Interestingly, artemisinin exhibited inhibitory effect on histone deacetylases (HDACs).

CONCLUSIONS:

Upregulated expression of tumor suppressor genes along with reduced expression of oncogenes significantly associated with growth stimulating signaling pathways in response to artemisinin treatment suggests its efficacy as an effective drug in breast cancer treatment.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Movimento Celular / Artemisininas / Inibidores de Histona Desacetilases / Transcriptoma / Antineoplásicos Tipo de estudo: Risk_factors_studies Limite: Female / Humans Idioma: En Revista: BMC Cancer Assunto da revista: NEOPLASIAS Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Índia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Movimento Celular / Artemisininas / Inibidores de Histona Desacetilases / Transcriptoma / Antineoplásicos Tipo de estudo: Risk_factors_studies Limite: Female / Humans Idioma: En Revista: BMC Cancer Assunto da revista: NEOPLASIAS Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Índia