Orostachys japonicus exerts antipancreatic cancer activity through induction of apoptosis and cell cycle arrest in PANC-1 cells.

Ji Hyun Kim,Deok Seon Ryu,Gi Suk Nam,Dong Seok Lee,Sung Hyun Kim

doi:10.1002/fsn3.1207

Ji Hyun Kim, Deok Seon Ryu + Show 3 more

Open Access

https://doi.org/10.1002/fsn3.1207

Copy DOI

Abstract

Targeted therapy at the molecular level is important for pancreatic cancer treatment. This study looked over the anticancer activity of Orostachys japonicus in a human pancreatic cancer cell line, PANC‐1. An ethyl acetate fraction containing quercetin, kaempferol, and flavonol glycosides from O. japonicus (OJE) exhibited significant anticancer activity against the PANC‐1. OJE activated caspase‐3, caspase‐8, and caspase‐9, leading to the induction of both intrinsic and extrinsic apoptosis pathways. It also inhibited cyclin D1, cyclin B1, and cyclin‐dependent kinase 4, representing cell cycle arrest at both G1/S and G2/M phases. In addition, OJE phosphorylated MAPKs such as p38, JNK, and ERK, which are important upstream signaling factors in apoptosis and arrest of cell cycle inducing system. In conclusion, OJE effectively exerted antipancreatic cancer activity via induction of apoptosis directed by both intrinsic and extrinsic pathways and arrest of cell cycle regulated at both G1/S and G2/M stages, which is activated by MAPKs, p38, JNK, and ERK.

Highlights

Pancreatic cancer is widely known as a fatal malignant tumor with a low survival rate (Qin, Hao, Tian, Xie, & Yang, 2012), and its incidence has been increasing every year worldwide (Akimoto, Lizuka, Kanematsu, Yoshida, & Takenaga, 2015)
The OJE‐induced phosphorylation of extracellular signal‐regulated kinase (ERK) was completely inhibited by ERK inhibitor U0126 (20 μM) in PANC‐1 cells (Figure 9d). These results represent that the activation of MAPKs affecting upstream signaling pathways of apoptosis and/or arrest of cell cycle in PANC‐1 cells by OJE correlates with the phosphorylation of MAPKs, including ERK
We attempted to establish the molecular mechanisms of OJE‐induced apoptosis and arrest of cell cycle in PANC‐1 pancreatic cancer cells

Summary

| INTRODUCTION

Pancreatic cancer is widely known as a fatal malignant tumor with a low survival rate (Qin, Hao, Tian, Xie, & Yang, 2012), and its incidence has been increasing every year worldwide (Akimoto, Lizuka, Kanematsu, Yoshida, & Takenaga, 2015). It is necessary to establish effective and safe therapies for pancreatic cancer that do not damage normal cells. The intrinsic pathway functions in response to cell damage and cellular stress stimuli. The extrinsic pathway is triggered by extracellular stimuli through death receptors at the cell surface, and its activation leads to the activation of procaspase‐8. Changes in the cellular components during the cell cycle depend on the inhibition or induction of apoptosis in cancer cells (Evan & Vousden, 2001). We studied the inducing effect of the ethyl acetate fraction (OJE) containing quercetin, kaempferol, and flavonol glycosides from O. japonicus on both apoptosis and cell cycle arrest via activation by MAPKs, p38, JNK, and ERK in a human pancreatic cancer cell line, PANC‐1

| MATERIALS AND METHODS

| DISCUSSION

Findings

ETHICAL APPROVAL