In vitro modulation the Notch pathway by piperine: A therapeutic strategy for docetaxel-resistant and non-resistant prostate cancer.

Wang, Rui-Tao; Liu, Hao-En; Sun, Hui-Yuan

Wang, Rui-Tao; Liu, Hao-En; Sun, Hui-Yuan.

Afiliación

Wang RT; Department of Urology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China.
Liu HE; Department of Urology, The Wujin Clinical College of Xuzhou Medical University, Changzhou, China.
Sun HY; Department of Urology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China.

Chem Biol Drug Des ; 103(6): e14562, 2024 Jun.

Article en En | MEDLINE | ID: mdl-38898371

ABSTRACT

ABSTRACT

Docetaxel (DTX) resistance poses a significant challenge in the treatment of prostate cancer (PCa), often leading to chemotherapy failure. This study investigates the ability of piperine, a compound derived from black pepper, to enhance the sensitivity of PCa cells to DTX and elucidates its underlying mechanism. We established a DTX-resistant PCa cell line, DU145/DTX, to conduct our experiments. Through a series of assays, including MTT for cell viability, flow cytometry for apoptosis, Transwell for cell migration and invasion, and western blot for protein expression analysis, we assessed the effects of piperine on these cellular functions and on the Notch signaling pathway components. Our results demonstrated that we successfully established the DTX-resistant PCa cell line DU145/DTX. Piperine effectively decreased the viability of both DU145 and its DTX-resistant counterpart, DU145/DTX, in a concentration and time-dependent manner when used alone and in combination with DTX. Notably, piperine also induced apoptosis and reduced the migration and invasion capabilities of these cells. At the molecular level, piperine down-regulated the Notch pathway by inhibiting Notch1 and Jagged1 signaling, as well as reducing the expression of downstream effectors Hey1 and hes family bHLH transcription factor 1. The study concludes that piperine's ability to modulate the Notch signaling pathway and induce apoptosis highlights its potential as a complementary treatment for DTX-resistant PCa, paving the way for the use of traditional Chinese medicinal compounds in modern oncology treatment strategies.

Asunto(s)

Alcaloides; Apoptosis; Benzodioxoles; Movimiento Celular; Docetaxel; Resistencia a Antineoplásicos; Piperidinas; Alcamidas Poliinsaturadas; Neoplasias de la Próstata; Transducción de Señal; Alcamidas Poliinsaturadas/farmacología; Alcamidas Poliinsaturadas/química; Humanos; Benzodioxoles/farmacología; Benzodioxoles/química; Alcaloides/farmacología; Alcaloides/química; Piperidinas/farmacología; Piperidinas/química; Docetaxel/farmacología; Masculino; Línea Celular Tumoral; Transducción de Señal/efectos de los fármacos; Resistencia a Antineoplásicos/efectos de los fármacos; Neoplasias de la Próstata/tratamiento farmacológico; Neoplasias de la Próstata/metabolismo; Neoplasias de la Próstata/patología; Apoptosis/efectos de los fármacos; Movimiento Celular/efectos de los fármacos; Receptores Notch/metabolismo; Antineoplásicos/farmacología; Antineoplásicos/química; Supervivencia Celular/efectos de los fármacos; Receptor Notch1/metabolismo

Palabras clave

Notch signaling pathway; chemoresistance; docetaxel; piperine; prostate cancer

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piperidinas / Neoplasias de la Próstata / Transducción de Señal / Movimiento Celular / Apoptosis / Resistencia a Antineoplásicos / Alcaloides / Benzodioxoles / Alcamidas Poliinsaturadas / Docetaxel Límite: Humans / Male Idioma: En Revista: Chem Biol Drug Des Asunto de la revista: BIOQUIMICA / FARMACIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

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