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Title: Eriocalyxin B induces apoptosis and cell cycle arrest in pancreatic adenocarcinoma cells through caspase- and p53-dependent pathways

Abstract

Pancreatic cancer is difficult to detect early and responds poorly to chemotherapy. A breakthrough in the development of new therapeutic agents is urgently needed. Eriocalyxin B (EriB), isolated from the Isodon eriocalyx plant, is an ent-kaurane diterpenoid with promise as a broad-spectrum anti-cancer agent. The anti-leukemic activity of EriB, including the underlying mechanisms involved, has been particularly well documented. In this study, we demonstrated for the first time EriB's potent cytotoxicity against four pancreatic adenocarcinoma cell lines, namely PANC-1, SW1990, CAPAN-1, and CAPAN-2. The effects were comparable to that of the chemotherapeutic camptothecin (CAM), but with much lower toxicity against normal human liver WRL68 cells. EriB's cytoxicity against CAPAN-2 cells was found to involve caspase-dependent apoptosis and cell cycle arrest at the G2/M phase. Moreover, the p53 pathway was found to be activated by EriB in these cells. Furthermore, in vivo studies showed that EriB inhibited the growth of human pancreatic tumor xenografts in BALB/c nude mice without significant secondary adverse effects. These results suggest that EriB should be considered a candidate for pancreatic cancer treatment. -- Highlights: ► We study Eriocalyxin B (EriB)'s cytotoxic effects on pancreatic cancer cell lines. ► EriB inhibits cell proliferation via mediation of apoptosismore » and cell cycle arrest. ► The effects are involved in caspase-dependent apoptosis and p53 pathway. ► In vivo study also shows EriB inhibits the growth of human pancreatic tumor. ► EriB can be a good candidate for chemotherapy in pancreatic cancer.« less

Authors:
 [1];  [2];  [2];  [3];  [2];  [3];  [2];  [4];  [1];  [2];  [2];  [3];  [2];  [3];  [2];  [2];  [1]
  1. School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China)
  2. (China)
  3. Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China)
  4. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, CAS, Yunnan (China)
Publication Date:
OSTI Identifier:
22215350
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 262; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CARCINOMAS; CELL CYCLE; CELL PROLIFERATION; CHEMOTHERAPY; IN VIVO; LIVER; MICE; PANCREAS; TOXICITY

Citation Formats

Li, Lin, Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, Yue, Grace G.L., State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, Lau, Clara B.S., Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, Sun, Handong, Fung, Kwok Pui, Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, Leung, Ping Chung, State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, Han, Quanbin, E-mail: simonhan@hkbu.edu.hk, State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, School of Chinese Medicine, The Hong Kong Baptist University, Hong Kong, and Leung, Po Sing, E-mail: psleung@cuhk.edu.hk. Eriocalyxin B induces apoptosis and cell cycle arrest in pancreatic adenocarcinoma cells through caspase- and p53-dependent pathways. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.04.021.
Li, Lin, Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, Yue, Grace G.L., State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, Lau, Clara B.S., Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, Sun, Handong, Fung, Kwok Pui, Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, Leung, Ping Chung, State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, Han, Quanbin, E-mail: simonhan@hkbu.edu.hk, State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, School of Chinese Medicine, The Hong Kong Baptist University, Hong Kong, & Leung, Po Sing, E-mail: psleung@cuhk.edu.hk. Eriocalyxin B induces apoptosis and cell cycle arrest in pancreatic adenocarcinoma cells through caspase- and p53-dependent pathways. United States. doi:10.1016/J.TAAP.2012.04.021.
Li, Lin, Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, Yue, Grace G.L., State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, Lau, Clara B.S., Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, Sun, Handong, Fung, Kwok Pui, Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, Leung, Ping Chung, State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, Han, Quanbin, E-mail: simonhan@hkbu.edu.hk, State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, School of Chinese Medicine, The Hong Kong Baptist University, Hong Kong, and Leung, Po Sing, E-mail: psleung@cuhk.edu.hk. Sun . "Eriocalyxin B induces apoptosis and cell cycle arrest in pancreatic adenocarcinoma cells through caspase- and p53-dependent pathways". United States. doi:10.1016/J.TAAP.2012.04.021.
@article{osti_22215350,
title = {Eriocalyxin B induces apoptosis and cell cycle arrest in pancreatic adenocarcinoma cells through caspase- and p53-dependent pathways},
author = {Li, Lin and Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong and Yue, Grace G.L. and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong and Lau, Clara B.S. and Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong and Sun, Handong and Fung, Kwok Pui and Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong and Leung, Ping Chung and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong and Han, Quanbin, E-mail: simonhan@hkbu.edu.hk and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong and School of Chinese Medicine, The Hong Kong Baptist University, Hong Kong and Leung, Po Sing, E-mail: psleung@cuhk.edu.hk},
abstractNote = {Pancreatic cancer is difficult to detect early and responds poorly to chemotherapy. A breakthrough in the development of new therapeutic agents is urgently needed. Eriocalyxin B (EriB), isolated from the Isodon eriocalyx plant, is an ent-kaurane diterpenoid with promise as a broad-spectrum anti-cancer agent. The anti-leukemic activity of EriB, including the underlying mechanisms involved, has been particularly well documented. In this study, we demonstrated for the first time EriB's potent cytotoxicity against four pancreatic adenocarcinoma cell lines, namely PANC-1, SW1990, CAPAN-1, and CAPAN-2. The effects were comparable to that of the chemotherapeutic camptothecin (CAM), but with much lower toxicity against normal human liver WRL68 cells. EriB's cytoxicity against CAPAN-2 cells was found to involve caspase-dependent apoptosis and cell cycle arrest at the G2/M phase. Moreover, the p53 pathway was found to be activated by EriB in these cells. Furthermore, in vivo studies showed that EriB inhibited the growth of human pancreatic tumor xenografts in BALB/c nude mice without significant secondary adverse effects. These results suggest that EriB should be considered a candidate for pancreatic cancer treatment. -- Highlights: ► We study Eriocalyxin B (EriB)'s cytotoxic effects on pancreatic cancer cell lines. ► EriB inhibits cell proliferation via mediation of apoptosis and cell cycle arrest. ► The effects are involved in caspase-dependent apoptosis and p53 pathway. ► In vivo study also shows EriB inhibits the growth of human pancreatic tumor. ► EriB can be a good candidate for chemotherapy in pancreatic cancer.},
doi = {10.1016/J.TAAP.2012.04.021},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 262,
place = {United States},
year = {2012},
month = {7}
}