Thidiazuron suppresses breast cancer via targeting miR-132 and dysregulation of the PI3K-Akt signaling pathway mediated by the miR-202-5p-PTEN axis.

Ibrahim, Hairul-Islam Mohamed; Ismail, Mohammad Bani; Ammar, Rebai Ben; Ahmed, Emad A

Ibrahim, Hairul-Islam Mohamed; Ismail, Mohammad Bani; Ammar, Rebai Ben; Ahmed, Emad A.

Afiliación

Ibrahim HM; Biological Sciences Department, College of Science, King Faisal University, Hofouf, Alhasa 31982, Saudi Arabia.
Ismail MB; Pondicherry Centre for Biological Science and Educational Trust, Pondicherry 605005, India.
Ammar RB; Biological Sciences Department, College of Science, King Faisal University, Hofouf, Alhasa 31982, Saudi Arabia.
Ahmed EA; Biological Sciences Department, College of Science, King Faisal University, Hofouf, Alhasa 31982, Saudi Arabia.

Biochem Cell Biol ; 99(3): 374-384, 2021 06.

Article en En | MEDLINE | ID: mdl-33103467

RESUMEN

Chemo-resistance and metastasis are the most common causes of breast cancer recurrence and death. Thidiazuron (TDZ) is a plant growth regulator (phytohormone) whose biological effects on humans and animals has not yet been determined. In this study, we investigated the anticancer activity of this phytohormone on the drug resistant-triple negative breast cancer cell line MDA-MB-231. Treatment of the breast cancer cells with TDZ (1-50 µmol/L) caused more stressful environment and induced a significant increase in active caspase-positive cells. In addition, TDZ treatment (5 and 10 µmol/L) significantly attenuated the migration and the invasiveness of these highly metastatic cancer cells. Mechanistically, TDZ reduces cancer progression and invasiveness by targeting miR-202-5p, which stimulates the expression of phosphatase and tensin homolog (PTEN), the tumor suppressor that downregulates the PI3K-Akt signaling pathway. Treatment with TDZ significantly upregulates miRNA-132, the suppressor of breast cancer proliferation, which is also implicated in dysregulation of the TEN-Akt-NFκB signaling pathway. Interestingly, our molecular docking analysis revealed a potential non-covalent interaction between TDZ and Akt, PTEN, and PI3K. These findings suggest that TDZ suppresses breast cancer metastasis by targeting miRNA-132, the miR-202-5p-PTEN axis, and the PI3K-Akt signaling pathway downstream.

Asunto(s)

Biomarcadores de Tumor/metabolismo; Neoplasias de la Mama/tratamiento farmacológico; Regulación Neoplásica de la Expresión Génica/efectos de los fármacos; MicroARNs/genética; Fosfohidrolasa PTEN/metabolismo; Compuestos de Fenilurea/farmacología; Tiadiazoles/farmacología; Apoptosis; Biomarcadores de Tumor/genética; Neoplasias de la Mama/genética; Neoplasias de la Mama/metabolismo; Neoplasias de la Mama/patología; Proliferación Celular; Femenino; Humanos; Invasividad Neoplásica; Fosfohidrolasa PTEN/genética; Fosfatidilinositol 3-Quinasas/genética; Fosfatidilinositol 3-Quinasas/metabolismo; Proteínas Proto-Oncogénicas c-akt/genética; Proteínas Proto-Oncogénicas c-akt/metabolismo; Células Tumorales Cultivadas

Palabras clave

PI3KAkt signaling pathway; breast cancer; cancer du sein; miR-132; thidiazuron; voie de signalisation PI3KAkt

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos de Fenilurea / Tiadiazoles / Neoplasias de la Mama / Biomarcadores de Tumor / Regulación Neoplásica de la Expresión Génica / MicroARNs / Fosfohidrolasa PTEN Límite: Female / Humans Idioma: En Revista: Biochem Cell Biol Asunto de la revista: BIOQUIMICA Año: 2021 Tipo del documento: Article País de afiliación: Arabia Saudita Pais de publicación: Canadá

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