Issue 8, 2022

Theaflavin-3,3′-di-gallate represses prostate cancer by activating the PKCδ/aSMase signaling pathway through a 67 kDa laminin receptor

Abstract

Prostate cancer is a major cause of morbidity and mortality in men. Theaflavin-3,3′-digallate (TF-3) is an important functional ingredient of black tea. We aimed to evaluate the cytotoxic effects of TF-3 on prostate cancer and to identify the underlying molecular mechanism. In this study, we explored the effects of TF-3 on prostate cancer in PC-3 cells and in NOD/SCID mice with prostate cancer. The results demonstrated that TF-3 inhibited prostate cancer cell proliferation by regulating the PKCδ/aSMase signaling pathway. The anti-prostate cancer effect of TF-3 was attributed to the expression of the 67 kDa laminin receptor (67LR), which is overexpressed in various cancers, playing a vital role in the growth and metastasis of tumor cells. Stable knockdown of 67LR could efficiently inhibit TF-3 induced apoptosis and cell cycle arrest in PC-3 cells, through interacting with the PKCδ/aSMase signaling pathway. In vivo studies also confirmed the above findings that TF-3 effectively inhibited tumor growth in terms of tumor volume. TF-3 treatment can significantly inhibit tumor growth and up-regulate the phosphorylation of PKCδ and the expression of aSMase in tumor xenografts developed by subcutaneously implanting PC-3 cells and 67LR-overexpressing PC-3 cells in mice. However, in tumor xenografts formed by subcutaneously implanting 67LR-knockdown PC-3 cells, TF-3 has no significant effect on PKCδ/aSMase pathway regulation and tumor growth inhibition.

Graphical abstract: Theaflavin-3,3′-di-gallate represses prostate cancer by activating the PKCδ/aSMase signaling pathway through a 67 kDa laminin receptor

Supplementary files

Article information

Article type
Paper
Submitted
10 Dec 2021
Accepted
04 Mar 2022
First published
18 Mar 2022

Food Funct., 2022,13, 4421-4431

Theaflavin-3,3′-di-gallate represses prostate cancer by activating the PKCδ/aSMase signaling pathway through a 67 kDa laminin receptor

L. Sun, S. Wen, Q. Li, X. Lai, R. Chen, Z. Zhang, J. Cao and S. Sun, Food Funct., 2022, 13, 4421 DOI: 10.1039/D1FO04198C

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