Baicalin suppresses lung cancer growth by targeting PDZ-binding kinase/T-LAK cell-originated protein kinase.

Xin Diao,Danfen Yang,Wentian Liu,Yu Chen

doi:10.1042/bsr20181692

Abstract

Baicalin is the main bioactive component extracted from the traditional Chinese medicine Baical Skullcap Root, and its anti-tumor activity has been studied in previous studies. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine/threonine protein kinase, is highly expressed in many cancer cells and stimulates the tumorigenic properties, and so, it is a pivotal target for agent to cure cancers. We reported for the first time that baicalin suppressed PBK/TOPK activities by directly binding with PBK/TOPK in vitro and in vivo. Ex vivo studies showed that baicalin suppressed PBK/TOPK activity in JB6 Cl41 cells and H441 lung cancer cells. Moreover, knockdown of PBK/TOPK in H441 cells decreased their sensitivity to baicalin. In vivo study indicated that injection of baicalin in H441 tumor-bearing mice effectively suppressed cancer growth. The PBK/TOPK downstream signaling molecules Histone H3 and ERK2 in tumor tissues were also decreased after baicalin treatment. Taken together, baicalin can inhibit proliferation of lung cancer cells as a PBK/TOPK inhibitor both in vitro and in vivo.

Highlights

PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine-threonine mitogen-activated protein kinase, is a member of the MEK protein family [1,2]
Previous studies showed that PBK/TOPK was highly expressed in multiple types of cancers and associated with poor prognosis, such as lymphoma, leukemia, melanoma, colorectal, breast and lung cancers, and cholangiocarcinoma [8,9,10,11,12,13,14]
A strong band was seen in baicalin–conjugated beads group, whereas no obvious band representing PBK/TOPK was observed in beads without baicalin group (Figure 1A)

Summary

Introduction

PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine-threonine mitogen-activated protein kinase, is a member of the MEK protein family [1,2]. It is involved in mitotic checkpoint of cell [3], DNA damage [4], tumor transformation and metastasis [5,6], and inflammation [7]. It was reported that TOPK exhibits high expression levels in cancer tissues but low expression levels in normal tissues [15]. These suggest that TOPK might be a prominent drug target for cancer chemotherapy. PBK/TOPK inhibitor HI-TOPK-032 [16], OTS964 [17] had brought some side-effects, which have been facing a critical challenge clinically [17]; we aimed to look for traditional medicine to inhibit PBK/TOPK activity

Objectives

Methods

Results

Conclusion