Latex ofEuphorbia antiquorum-induced S-phase arrest via active ATM kinase and MAPK pathways in human cervical cancer HeLa cells

Abstract

Latex of Euphorbia antiquorum (EA) has demonstrated great chemotherapeutic potential for cancer. However, the mechanisms of anti-proliferation of EA on cancer cell remain to be further investigated. The purpose of this study was to explore the influence of EA in human cervical cancer cells. Here, the cell cycle distribution by flow cytometry was examined and the protein expression by the western blotting methods was analyzed. From the cytometric results it was shown that EA-induced S-phase arrest in a concentration manner both in human cervical cancer HeLa and CaSki cells. According the western blot results it was illustrated that EA could downregulate early cyclin E1-Cdk2; and cyclin A-Cdc2 provides a significant additional quantity of S-phase promotion, that in turn promoted the expression of p21(waf1/cip1) and p27(kip1) which were the inhibitors in the complex of cyclin A and Cdc2 that led to cell cycle arrest. Moreover, EA promoted the activation of ataxia telangiectasia mutated (ATM) and check-point kinase-2 (Chk2); however, it negatively regulated the expression of Topoisomerases I and II, Cdc25A, and Cdc25C signaling. Caffeine, an ATM/ATR inhibitor significantly reversed EA downregulation in the levels of Cdc25A. Furthermore, JNK inhibitor SP600125 and p38 MAPK inhibitor SB203580 both could reverse the EA upregulation of the protein of Chk2 level, significantly. This study, therefore, revealed that EA could downregulate topoisomerase, and activate ATM kinase, which then induce parallel Chk 1/2 and MAPK signaling pathways to promote the degradation of Cdc25A to induced S-phase arrest in human cervical cancer HeLa cells.

Exploration of the molecular mechanisms of cervical cancer based on mRNA expression profiles and predicted microRNA interactions

“…Overexpression of miR-424 inhibited the expression of CHEK1 and p-CHEK1 at residue Ser345, and decreased the activity of the luciferase-reporter containing the 3′-untranslated region of CHEK1. Hsieh et al ( 40 ) revealed that Euphorbia antiquorum extracts could downregulate topoisomerase and activate ATM kinase, inducing the CHEK1 / 2 and mitogen activated protein kinase signaling pathways, and promoting the degradation of cell division cycle 25A to induce S-phase arrest in HeLa cells.…”

Protodioscin Induces Apoptosis Through ROS-Mediated Endoplasmic Reticulum Stress via the JNK/p38 Activation Pathways in Human Cervical Cancer Cells

“…MAPKs are involved in many aspects of the control of cellular proliferation and apoptosis and have been implicated in the regulation of gene expression in the ER stress signaling cascade in cervical cancer [24, 25]. We performed Western blotting to analyze MAPK signaling pathways induced by PD in cervical cancer cells, and found that PD induced apoptosis through activation of JNK and p38 expression (Fig.…”

The effect of ionizing radiation on the subcellular localization and kinase activity of protein kinase CK2 in human non-small cell lung cancer cells

“…Our data agree with Carroll and Marshak (1989), they found a higher CK2 activity in S phase cells than that in quiescent cells in WI38 human lung fibroblasts. The increase in S phase was reported to be related to ATM, which is a CK2 phosphorylation substrate, activation (Hsieh et al 2015;Lee et al 2018), indicating the increase in CK2 activity after IR is related to the DNA damage repair process. Almost all eukaryotic cells showed an increase in G2/M phase after radiation (Xu B et al 2002).…”