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Cancer Cell International

, 10:25

First Online: 04 August 2010Received: 24 February 2010Accepted: 04 August 2010

Abstract

BackgroundLeukemia 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.

ResultsWhen HL-60 cells were treated with different concentration of lycorine, the expression of p21 and TNF-α 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 IκB phosphorylation and blocked NF-κB nuclear import. Cytochrome c was released from mitochondria as observed with confocal laser microscopy.

ConclusionsThe TNF-α 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.

List of abbreviationsAPLacute promyelogenous leukemia

Bcl2B cell lymphoma gene 2

BidBH3-interacting death domain

Cdc2cell division cycle 2

Cdk2cyclin dependent kinase 2

CMLchronic myelogenous leukemia

Cy3cyanine 3

Mcl-1myeloid cell leukemia 1

RT-PCRreverse transcriptase- polymerase chain reaction

SABCstreptavidin-biotin complex

SDS-PAGEsodium dodecyl sulfate polyacrylamide gel electrophoresis

TGF-βtransforming growth factor-beta

TNFtumor necrosis factor

TRAILtumor necrosis factor-related apoptosis-inducing ligand

TRAF1TNF receptor-associated factor 1

Electronic supplementary materialThe online version of this article doi:10.1186-1475-2867-10-25 contains supplementary material, which is available to authorized users.

Jing Liu, Ji-liang Hu contributed equally to this work.

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Autor: Jing Liu - Ji-liang Hu - Bi-Wei Shi - Yan He - Wei-Xin Hu

Fuente: https://link.springer.com/



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