Up-regulation of p21 and TNF-alpha is mediated in lycorine-induced death of HL-60 cells.
BACKGROUND
Leukemia is one of the most life-threatening cancers today, and acute promyelogenous leukemia (APL) is a common type of leukemia. Many natural compounds have already been found to exhibit significant anti-tumor effects. Lycorine, a natural alkaloid extracted from Amaryllidaceae, exhibited anti-leukemia effects in vitro and in vivo. The survival rate of HL-60 cells exposed to lycorine was decreased, cell growth was slowed down, and cell regeneration potential was inhibited. HL-60 cells exhibited typical apoptotic characteristic. Lycorine can suppress leukemia growth and reduce cell survival and inducing apoptosis of tumor cells. The purpose of this work is to elucidate the mechanism by which lycorine induces APL cells.


RESULTS
When HL-60 cells were treated with different concentration of lycorine, the expression of p21 and TNF-alpha was up-regulated in a concentration-dependent manner as shown by real-time quantitative reverse transcriptase-polymerase chain reaction and Western blotting. Lycorine also down-regulated p21-related gene expression, including Cdc2, Cyclin B, Cdk2 and Cyclin E, promoted Bid truncation, decreased IkappaB phosphorylation and blocked NF-kappaB nuclear import. Cytochrome c was released from mitochondria as observed with confocal laser microscopy.


CONCLUSIONS
The TNF-alpha signal transduction pathway and p21-mediated cell-cycle inhibition were involved in the apoptosis of HL-60 cells induced by lycorine. These results contribute to the development of new lycorine-based anti-leukemia drugs.
Liu
Jing
J
Molecular Biology Research Center, School of Biological Science and Technology, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, People's Republic of China.
Hu
Ji-Liang
JL
Molecular Biology Research Center, School of Biological Science and Technology, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, People's Republic of China.
Shi
Bi-Wei
BW
Molecular Biology Research Center, School of Biological Science and Technology, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, People's Republic of China.
He
Yan
Y
Molecular Biology Research Center, School of Biological Science and Technology, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, People's Republic of China.
Hu
Wei-Xin
WX
Molecular Biology Research Center, School of Biological Science and Technology, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, People's Republic of China.