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A novel compound modified from tanshinone inhibits tumor growth in vivo via activation of the intrinsic apoptotic pathway
Tian H.-L.1; Yu T.2; Xu N.-N.1; Feng C.1; Zhou L.-Y.1; Luo H.-W.4; Chang D.C.1; Le X.-F.3; Luo K.Q.2
2010-11-01
Source PublicationCancer Letters
ISSN03043835
Volume297Issue:1Pages:18-30
Abstract

A novel compound, acetyltanshinone IIA (ATA) was obtained from chemical modifications of tanshinone TIIA (TIIA) isolated from a medicinal plant, Salvia miltiorrhiza. ATA exhibited increased water solubility and stronger apoptotic activity on multiple cancer cell lines than TIIA. ATA displayed a higher growth inhibition ability on breast cancer especially HER2 positive cells than normal cells and it inhibited xenografted tumor growth in mice. Mechanistic studies showed that ATA could induce significant reactive oxygen species (ROS) generation, Bax translocation to mitochondria, resulting in mitochondria damage, cytochrome c release, caspase-3 activation and apoptotic cell death. ATA-mediated ROS production and its downstream apoptotic events could be blocked by an antioxidant agent, propyl gallate, indicating the prominent role of ROS in ATA-induced apoptosis. Overexpression of Bcl-2 protein reduced ATA-induced cell death. In conclusion, ATA is a novel anticancer agent with potent in vitro and in vivo anticancer ability. ROS-mediated Bax activation should be the mechanism by which ATA induces apoptosis and inhibits tumor growth. © 2010 Elsevier Ireland Ltd.

KeywordAnticancer Drug Apoptosis Breast Cancer Reactive Oxygen Species Tanshinone Iia
DOI10.1016/j.canlet.2010.04.020
URLView the original
Indexed BySCI
Language英语
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000282715000003
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Cited Times [WOS]:34   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Hong Kong University of Science and Technology
2.Nanyang Technological University
3.University of Texas MD Anderson Cancer Center
4.China Pharmaceutical University
Recommended Citation
GB/T 7714
Tian H.-L.,Yu T.,Xu N.-N.,et al. A novel compound modified from tanshinone inhibits tumor growth in vivo via activation of the intrinsic apoptotic pathway[J]. Cancer Letters,2010,297(1):18-30.
APA Tian H.-L..,Yu T..,Xu N.-N..,Feng C..,Zhou L.-Y..,...&Luo K.Q..(2010).A novel compound modified from tanshinone inhibits tumor growth in vivo via activation of the intrinsic apoptotic pathway.Cancer Letters,297(1),18-30.
MLA Tian H.-L.,et al."A novel compound modified from tanshinone inhibits tumor growth in vivo via activation of the intrinsic apoptotic pathway".Cancer Letters 297.1(2010):18-30.
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