title: The Loss of a Sugar Chain at C(3) Position Enhances Stemucronatoside K-Induced Apoptosis, Cell Cycle Arrest, and Hedgehog Pathway Inhibition in HT-29 Cells.
abstract: Stemucronatoside K (SMK) and its aglycone stephanthraniline A (STA) are the most representative of a series of novel C21steriodal compounds that we have previously isolated from Asclepiadaceae plants. The objectives of this study were to investigate the antitumor activity of SMK and STA, and clarify the effect of the sugar chain at the C(3) position. Our results showed that both SMK and STA decreased the growth of HT-29 cells in a dose- and time-dependent manner. Meanwhile, STA showed much stronger inhibitory effect than SMK. Treatment of HT-29 cells with STA increased the apoptotic cell numbers and the protein expression of cleaved caspase 3 and cleaved-PARP. G1 phase cell cycle arrest and decreased expression of cyclin D1 and cyclin-dependent kinases 4 were also observed after STA treatment. Furthermore, STA reduced the mRNA levels of four Hedgehog pathway components (GLI1, GLI2, GLI3, and PTCH1) and suppressed Shh-induced Hedgehog pathway activation in a concentration-dependent manner. These results indicated that SMK and STA could inhibit the growth of HT-29 cells by inducing apoptosis, cell cycle arrest, and hedgehog pathway inhibition. The loss of sugar chain at C(3) position could enhance SMK's activity. This study is beneficial to understand the use of natural C21steroids as antitumor lead compounds.
authors.affiliation: Zhejiang Cancer Hospital, Hangzhou, 310022, P. R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Zhejiang Cancer Hospital, Hangzhou, 310022, P. R. China.
authors.forename: Li-Fei
authors.initials: LF
authors.lastname: Zhou
authors.affiliation: Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, P. R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, P. R. China.
authors.forename: Hua-Jun
authors.initials: HJ
authors.lastname: Zhao
authors.affiliation: Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, P. R. China.
authors.forename: Yi-Qi
authors.initials: YQ
authors.lastname: Wang
authors.affiliation: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Tianmushan Road 182, Hangzhou, 310013, P. R. China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Li
authors.affiliation: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Tianmushan Road 182, Hangzhou, 310013, P. R. China.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Ye
authors.affiliation: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Tianmushan Road 182, Hangzhou, 310013, P. R. China.
authors.forename: Feng-Yang
authors.initials: FY
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002241:Carbohydrates / Q000737:chemistry*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019073:HT29 Cells; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D002241:Carbohydrates; D053823:Hedgehog Proteins; D012503:Saponins; C531974:stemucronatoside K
keywords: Apoptosis; C21 Steroid; Cell cycle arrest; Hedgehog pathway; Structure-activity relationship