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

• Published in: Phytomedicine (Stuttgart) 2013-04, Vol.20 (6), p.512-520
• Main Authors: Liu, Linna, Wang, Jingjie, Shi, Lei, Zhang, Wenjuan, Du, Xiaoyan, Wang, Zhipeng, Zhang, Yan
• Format: Article
• Language: English
• Subjects: Acorus - chemistry; Allylbenzene Derivatives; Animals; Anisoles - pharmacology; Anisoles - therapeutic use; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Asarabacca; Asarone; beta-Galactosidase - metabolism; Care and treatment; Cell Line, Tumor; Cell Proliferation - drug effects; Cell senescence; Cell Transformation, Neoplastic - drug effects; Cellular Senescence - drug effects; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Disease Models, Animal; Gene expression; Gene Expression Regulation, Neoplastic; Health aspects; HT29 Cells; Humans; Lamin Type B - metabolism; Lamins; Lamins - metabolism; Male; Medicine, Botanic; Medicine, Herbal; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Mice, Nude; Oct-1; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Transplantation, Heterologous
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2012.12.008

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.