β-Asarone induces senescence in colorectal cancer cells by inducing lamin B1 expression.
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.
Department of Pharmaceutics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Linna
L
Liu
Jingjie
J
Wang
Lei
L
Shi
Wenjuan
W
Zhang
Xiaoyan
X
Du
Zhipeng
Z
Wang
Yan
Y
Zhang
D029023:Acorus / Q000737:chemistry*; D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000494:pharmacology / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D034921:Lamin Type B / Q000378:metabolism*; D034882:Lamins / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D001616:beta-Galactosidase / Q000378:metabolism
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D000972:Antineoplastic Agents, Phytogenic; D034921:Lamin Type B; D034882:Lamins; D010936:Plant Extracts; C012195:asarone; D001616:beta-Galactosidase