β-Asarone induces senescence in colorectal cancer cells by inducing lamin B1 expression.

Abstract

Colorectal cancer is a leading cause of cancer mortality with a complex carcinogenesis that includes reduced cellular senescence. Lamin proteins are decreased in senescing cells, and frequently decreased in malignancies. This study identified a new drug candidate for colorectal cancer that appears to target cell senescence via a lamin protein. β-Asarone (1-propenyl-2,4,5-methoxybenzol) is a compound from the traditional medical herb Acorus calamus Linn. This study tested the in vitro and in vivo effects of β-asarone on colorectal cancer cells by testing cell viability using human colorectal cell lines HT29 and SW480 in MTT assays; tumorigenesis using xenografts in nude mice and a mouse model of colorectal cancer; cell senescence using senescence-associated β-galactosidase activity; and expression of cancer and senescence-related proteins, specifically lamins, Oct-1, p53, p21, and p15, by Western blot. β-Asarone appeared to increase expression of lamin B1, p53, p21, but not lamin A/C. β-Asarone regulates p15 expression by regulation of Oct-1 binding. Collectively, the results suggested that β-asarone inhibits colon cancer formation in vivo and in vitro by inducing senescence. Since β-asarone induced lamin B1 expression, a model is proposed in which β-asarone inhibits colorectal cancer by inducing senescence through lamin B1.

• Authors: Linna Liu, Jingjie Wang, Lei Shi, Wenjuan Zhang, Xiaoyan Du, Zhipeng Wang, Yan Zhang
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 20 Issue 6 Pg. 512-20 (Apr 15 2013) ISSN: 1618-095X [Electronic] Germany
• PMID: 23357361 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013. Published by Elsevier GmbH.

Chemical References

• Allylbenzene Derivatives
• Anisoles
• Antineoplastic Agents, Phytogenic
• Lamin Type B
• Lamins
• Plant Extracts
• asarone
• lamin B1
• beta-Galactosidase

Topics

• Acorus (chemistry)
• Allylbenzene Derivatives
• Animals
• Anisoles (pharmacology, therapeutic use)
• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Transformation, Neoplastic (drug effects)
• Cellular Senescence (drug effects)
• Colorectal Neoplasms (drug therapy, metabolism)
• Disease Models, Animal
• Gene Expression Regulation, Neoplastic
• HT29 Cells
• Humans
• Lamin Type B (metabolism)
• Lamins (metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred ICR
• Mice, Nude
• Phytotherapy
• Plant Extracts (pharmacology, therapeutic use)
• Transplantation, Heterologous
• beta-Galactosidase (metabolism)