Premium
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
Author(s) -
Zhou Xia,
Zhou LiFei,
Yang Bo,
Zhao HuaJun,
Wang YiQi,
Li XiaoYu,
Ye YiPing,
Chen FengYang
Publication year - 2016
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201600054
Subject(s) - chemistry , apoptosis , cell cycle checkpoint , cell cycle , hedgehog signaling pathway , aglycone , cyclin d1 , hedgehog , cyclin , cell growth , cyclin b1 , microbiology and biotechnology , biochemistry , signal transduction , stereochemistry , cyclin dependent kinase 1 , biology , glycoside
Stemucronatoside K ( SMK ) and its aglycone stephanthraniline A ( STA ) are the most representative of a series of novel C 21 steriodal 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 ( GLI 1, GLI 2, GLI 3, and PTCH 1) 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 C 21 steroids as antitumor lead compounds.