title: Tanshinone I induces cyclin D1 proteasomal degradation in an ERK1/2 dependent way in human colorectal cancer cells.
abstract: Tanshinone I (TAN I) as one of the naturally occurring diterpenes from Salvia miltiorrhizae Bunge (Danshen) has been reported to exhibit an anti-cancer activity. However, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to elucidate the biological mechanism by which TAN I may induce the inhibition of cell growth in human colorectal cancer cells. The treatment of TAN I suppressed the cell proliferation in HCT116 and SW480 cells and decreased the level of cyclin D1 protein. However, the mRNA level of cyclin D1 did not changed by TAN I treatment. Inhibition of proteasomal degradation by MG132 blocked TAN I-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with TAN I. In addition, phosphorylation of cyclin D1 at threonine-286 was increased by TAN I and a point mutation of threonine-286 to alanine attenuated TAN I-mediated cyclin D1 downregulation. Inhibition of ERK1/2 suppressed cyclin D1 phosphorylation and subsequent downregulation by TAN I. From these results, we suggest that TAN I-mediated cyclin D1 downregulation may result from proteasomal degradation through its ERK1/2-mediated phosphorylation of threonine-286. In conclusion, the current study provides new mechanistic link between TAN I, cyclin D1 downregulation and cell growth in human colorectal cancer cells.
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea.
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea.
authors.forename: Gwang Hun
authors.initials: GH
authors.lastname: Park
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea.
authors.forename: Hyun Ji
authors.initials: HJ
authors.lastname: Eo
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea.
authors.forename: Hun Min
authors.initials: HM
authors.lastname: Song
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea.
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Medicinal Plant Resources, Andong National University, Andong 760749, Republic of Korea.
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Kwon
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea; Department of Medicinal Plant Resources, Andong National University, Andong 760749, Republic of Korea; Insititute of Agricultural Science and Technology, Andong National University, Andong 760749, Republic of Korea.
authors.forename: Jin Suk
authors.initials: JS
authors.lastname: Koo
authors.affiliation: Department of Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea; Department of Medicinal Plant Resources, Andong National University, Andong 760749, Republic of Korea; Insititute of Agricultural Science and Technology, Andong National University, Andong 760749, Republic of Korea. Electronic address: jjb0403@anu.ac.kr.
authors.forename: Jin Boo
authors.initials: JB
authors.lastname: Jeong
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; C530104:CCND1 protein, human; C021751:tanshinone; D019938:Cyclin D1; D046988:Proteasome Endopeptidase Complex
keywords: Cancer chemoprevention; Colorectal cancer; Cyclin D1; Danshen; Tanshinone I