Inhibitory action of chamaejasmin A against human HEP-2 epithelial cells: effect on tubulin protein.
In this work, the anticancer activity of chamaejasmin A was studied by evaluating its in vitro cytotoxicity against several cell lines (CAL-27, UMSCC-1, UMSCCG19, HEP-2 and Vero cells) using the 3-(4,5)-dimethylthiazoly1)-3,5-diphenytetrazolium bromide assay. Results indicated chamaejasmin A shows more notable anticancer activity against HEP-2 cells, with IC(50) values of 3.48 μM. Furthermore, western blot analysis showed that chamaejasmin A is able to increase the expression of β-tubulin (TB), but not α-TB. In vivo, chamaejasmin A intake through gavage resulted in β-TB depolymerization inhibition in HEP-2 tumors. In silico simulations indicated that chamaejasmin A specifically interacts with the binding site which is located at the top of β-TB, thanks to the presence of strong hydrophobic effects between the core templates and the hydrophobic surface of the TB protein active site, associated with two strong H-bonds. The binding energy (E (inter)) was calculated to be -129.40 kcal mol(-1). Results above suggest that chamaejasmin A possesses anti-cancer properties relating to β-TB depolymerization inhibition.
Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin, 150001, People's Republic of China.
Yan
Y
Zhao
Fenglian
F
Wu
Yu
Y
Wang
Shengwu
S
Chen
Guojun
G
Han
Ming
M
Liu
Dejun
D
Jin
D000818:Animals; D044946:Biflavonoids / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019295:Computational Biology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D006860:Hydrogen Bonding / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D058105:Polymerization / Q000187:drug effects; D055672:Static Electricity; D013816:Thermodynamics; D013997:Time Factors; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D044946:Biflavonoids; D014404:Tubulin; C511440:chamaejasmine