The effects of cucurbitacin E on GADD45β-trigger G2/M arrest and JNK-independent pathway in brain cancer cells.

An‐Chin Cheng,Yi‐Chiang Hsu,Chiang‐Chin Tsai

doi:10.1111/jcmm.14250

An‐Chin Cheng, Yi‐Chiang Hsu + Show 1 more

Open Access

https://doi.org/10.1111/jcmm.14250

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Abstract

Cucurbitacin E (CuE), an active compound of the cucurbitacin family, possesses a variety of pharmacological functions and chemotherapy potential. Cucurbitacin E exhibits inhibitory effects in several types of cancer; however, its anticancer effects on brain cancer remain obscure and require further interpretation. In this study, efforts were initiated to inspect whether CuE can contribute to anti‐proliferation in human brain malignant glioma GBM 8401 cells and glioblastoma‐astrocytoma U‐87‐MG cells. An MTT assay measured CuE's inhibitory effect on the growth of glioblastomas (GBMs). A flow cytometry approach was used for the assessment of DNA content and cell cycle analysis. DNA damage 45β (GADD45β) gene expression and CDC2/cyclin‐B1 disassociation were investigated by quantitative real‐time PCR and Western blot analysis. Based on our results, CuE showed growth‐inhibiting effects on GBM 8401 and U‐87‐MG cells. Moreover, GADD45β caused the accumulation of CuE‐treated G2/M‐phase cells. The disassociation of the CDC2/cyclin‐B1 complex demonstrated the known effects of CuE against GBM 8401 and U‐87‐MG cancer cells. Additionally, CuE may also exert antitumour activities in established brain cancer cells. In conclusion, CuE inhibited cell proliferation and induced mitosis delay in cancer cells, suggesting its potential applicability as an antitumour agent.

Highlights

A previous study reported that brain cancer is one of the most in‐ vasive and malignant cancers in developed countries.[1]
The results revealed that the in‐ hibition of GADD45β activity significantly suppressed Cucurbitacin E (CuE)‐induced G2/M arrest in GBM8401 and U‐87‐MG cells (Figure 4B,C), implying that GADD45β could regulate the survival of GBM8401 and U‐87‐ MG cells via CuE
Our findings provide experimental evidence indicating that CuE may irreversibly arrest GBM8401 and U‐87‐MG cell growth

Summary

| INTRODUCTION

A previous study reported that brain cancer is one of the most in‐ vasive and malignant cancers in developed countries.[1]. Cucurbitacins have been widely used in inhibi‐ tion of cancer cell progression as medicinal herbs throughout Asia.[7] In recent years, there is a growing interest in this herb because of its presumed beneficial pharmacological properties as anti‐inflam‐ matory[8] and antitumour agents.[9]. Glioblastomas (GBMs) are highly invasive and recurrence brain tumours,[15] and have been shown to harbour therapy‐resistant can‐ cer stem cells (CSCs), and this is the main cause of death.[16,17] Recent studies indicated that GBMs contain a subpopulation of glioma‐ini‐ tiating tumour cells which exhibits stem cell characteristics and may be responsible for in vivo tumour growth.[18,19] we chose the GBM 8401 and glioblastoma‐astrocytoma U‐87‐MG cells as human brain cancer model to analyse the antitumour activity of CuE. We expect that our study may provide a scientific foundation and technological support for brain GBM therapy

| MATERIALS AND METHODS

| DISCUSSION