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.

• Authors: Lin Li, Grace G L Yue, Clara B S Lau, Handong Sun, Kwok Pui Fung, Ping Chung Leung, Quanbin Han, Po Sing Leung
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 262 Issue 1 Pg. 80-90 (Jul 01 2012) ISSN: 1096-0333 [Electronic] United States
• PMID: 22561874 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Diterpenes
• Tumor Suppressor Protein p53
• eriocalyxin B
• Caspases
• Camptothecin

Topics

• Adenocarcinoma (drug therapy, pathology)
• Animals
• Antineoplastic Agents, Phytogenic (pharmacology, toxicity)
• Apoptosis (drug effects)
• Camptothecin (pharmacology, toxicity)
• Caspases (metabolism)
• Cell Line
• Cell Line, Tumor
• Diterpenes (pharmacology, toxicity)
• G2 Phase Cell Cycle Checkpoints (drug effects)
• Humans
• Liver (drug effects, metabolism)
• M Phase Cell Cycle Checkpoints (drug effects)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Pancreatic Neoplasms (drug therapy, pathology)
• Tumor Suppressor Protein p53 (metabolism)
• Xenograft Model Antitumor Assays