Trichosanthin down-regulated p210Bcr-Abl and enhanced imatinib-induced growth arrest in chronic myelogenous leukemia cell line K562.
OBJECTIVE
Trichosanthin (TCS), an active component extracted from the root tubers of traditional Chinese medical herb Tian-Hua-Fen of the Cucurbitaceae family, has long been used for medical purpose in China; there is increasing interest in developing TCS as cancer therapeutic agents. The present study was to investigate the growth arrest of K562 cells and its molecular mechanisms, which the drugs induced by TCS and the possible functional interaction of TCS with imatinib (STI571) to K562 cells.


METHODS
Trypan blue exclusive staining was used to access the cell growth inhibition; western blot was used to evaluate the p210(Bcr-Abl), phosphorylated tyrosine kinase (PTK), and some signaling molecules involving in cell proliferation and apoptosis in K562 cells.


RESULTS
TCS and imatinib inhibited K562 cells at a time- and dose-dependent manners, respectively; TCS down-regulated p210(Bcr-Abl) at a time- and dose-dependent manners; TCS synergistically enhanced imatinib-induced K562 cell growth arrest and down-regulation of p210(Bcr-Abl), PTK activities, procaspase-3, Hsp90,NF-kappaB and PKC.


CONCLUSIONS
The results suggest that TCS not only by itself involves but also synergizes activities of imatinib to induce K562 cell growth arrest, down-regulation of p210(Bcr-Abl) and its downstream signals and to stimulate the effect of the tyrosine kinase inhibition.
Zhang
Kunzhong
K
Institute of Clinical Pharmacology, School of Pharmacy, Fujian Medical University, Fujian 350004, People's Republic China.
Xu
Jianhua
J
Huang
Xiuwang
X
Wu
Lixian
L
Wen
Caixia
C
Hu
Yingying
Y
Su
Yu
Y
Chen
Yuanzhong
Y
Zhang
Zhiqiang
Z
D001549:Benzamides; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004357:Drug Synergism; D016313:Genes, abl / Q000187:drug effects*; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells / Q000187:drug effects*; D008958:Models, Molecular; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D015978:Trichosanthin / Q000737:chemistry / Q000494:pharmacology*
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D015978:Trichosanthin; D000068877:Imatinib Mesylate