Midkine downregulation increases the efficacy of quercetin on prostate cancer stem cell survival and migration through PI3K/AKT and MAPK/ERK pathway

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Suat ErdoganGulperi Oktem

Abstract

To examine the functions of growth factor midkine (MK) and a flavonoid quercetin on survival, apoptosis and migration of prostate cancer (PCa) stem cells (CSCs). CD44+/CD133+ and CD44+ stem cells were isolated from PC3 and LNCaP cells, respectively by magnetic-activated cell sorting system. 3D cell culture was used to evaluate the ability of quercetin, MK siRNA, and the combination of both to inhibit spheroid formation, apoptosis and cell cycle arrest. Image-based cytometer, RT-qPCR, Western blotting and transwell migration assays were performed. Quercetin treatment for 24-72 h inhibited PC3 and CD44+/CD133+ stem cell proliferation in a time- and dose-dependent manner. Knockdown of endogenous MK expression significantly suppressed proliferation of CD44+/CD133+ and CD44+ cells as well as their parent cells. Co-administration of MK siRNA and quercetin reduced the cell survival, induced apoptosis and caused G1 phase cell cycle arrest more effectively than the individual therapy. Knockdown of MK significantly enhanced the inhibitory effect of quercetin on CD44+/CD133+ migration and spheroid formation. In addition, the combined therapy inhibited the phosphorylation of PI3K, AKT and ERK1/2, and reduced the protein expression of p38, ...Continue Reading

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Citations

May 9, 2019·Biomolecules·Dharambir KashyapSardul Singh Sandhu
Dec 31, 2019·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Maimaiti MikeliTsutomu Tanabe
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Jul 2, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Soudeh Ghafouri-FardSeyed Abdulmajid Ayatollahi
Jul 18, 2021·Seminars in Cancer Biology·Man ChuZhi-Wei Wang

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