Polypeptide Fraction fromArca subcrenataInduces Apoptosis and G2/M Phase Arrest in HeLa Cells via ROS-Mediated MAPKs Pathways

Abstract

Arca subcrenata is documented in the literature of marine Traditional Chinese Medicine. Polypeptide fraction from A. subcrenata, coded as P2, was demonstrated to possess significant antitumor activity in our previous study. However, the underlying mechanism remains undefined. The present study was carried out to investigate the underlying antitumor mechanism of P2 in human cervical cancer HeLa cells by MTT, FCM, LSCM, and western blot assays. The results revealed that P2 significantly induced apoptosis of HeLa cells in a concentration- and time-dependent manner. High level of ROS was provoked by P2, which was in turn responsible for induction of apoptosis through activation of intrinsic mitochondrial pathway and JNK1/2, p38 MAPK pathways, as well as inhibition of ERK1/2 pathway, as evidenced by the abrogation of P2's effect on HeLa cells preincubated with the ROS scavenger NAC. P2 also was observed to display significant effect on G2/M phase arrest by downregulating the expression of cyclin B1/cdc2 complex and upregulating the expression of p21. These findings demonstrate that P2 induces apoptosis and G2/M phase arrest in HeLa cells through ROS-mediated MAPKs pathways, suggesting that P2 would be worth investigating as a promising agent within the scope of marine drugs for treatment of cervical cancer.

A novel function of IMPA2, plays a tumor-promoting role in cervical cancer

“…The KEGG enrichment analysis for the identification of pathways unveils possible involvement of MAPK signaling pathway. MAPK plays an important role in regulating cell proliferation 32 , differentiation 33,34 , cell cycle arrest 35 , apoptosis 24,36,37 , immune function 38 , and autophagy 36,39 . The MAPK signaling pathway is shared by four distinct cascades 40 , including Jun amino-terminal kinases (JNK1/ 2/3), extracellular signal-related kinases (ERK1/2), p38-MAPK and ERK5.…”

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

“…Naphtho [1, 2-β] furan-4, 5-dione (NFD) induces cell apoptosis through activation of JNK and ERK pathways, while ERK protects cells from apoptosis by regulating Bcl-2 family proteins in MDA-MB-231 cells [46]. The polypeptide fraction from Arca subcrenata activates the JNK1/2 and p38 pathways and inactivates the ERK1/2 pathway, and ROS plays a critical role in polypeptide fraction-inhibited growth and induced apoptosis on the MAPK pathways of HeLa cells [47]. In agreement with this finding, we also observed up-regulation of p38 and JNK phosphorylation in PD-treated cervical cancer cells.…”

EIF3D silencing suppresses renal cell carcinoma tumorigenesis via inducing G2/M arrest through downregulation of Cyclin B1/CDK1 signaling

“…G2/M checkpoint in eukaryotic cells is an important cell cycle DNA damage checkpoint, which play an important role in regulating cell cycle progression (16). G2/M arrest is considered to prevent eukaryotic cells from entering the process of mitosis and could be an effective antitumor strategy (17,18). In eukaryotes, cell cycle is regulated by cyclins, cyclin-dependent kinases (CDKs) and cyclin-dependent kinase inhibitors (CDKIs) (19).…”