Piplartine induces inhibition of leukemia cell proliferation triggering both apoptosis and necrosis pathways
Piplartine induces inhibition of leukemia cell proliferation triggering both apoptosis and necrosis pathways
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DOI：
10.1016/j.tiv.2006.07.007
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发表时间：
2007-02-01
影响因子：
3.2
通讯作者：
Costa-Lotufo, Leticia Veras
中科院分区：
文献类型：
--
作者：
Bezerra, Daniel Pereira;Gadelha Militao, Gardenia Carmen;Costa-Lotufo, Leticia Veras
胡椒碱{5，6-二氢-1-[1-氧代-3-（3，4，5-三甲氧基苯基）-2-丙烯基]-2（1H）吡啶酮}是胡椒属植物的生物碱/酰胺成分。本研究采用台盼蓝拒染法观察了匹普拉汀对人白血病细胞株HL-60、K562、Jukart和Molt-4的增殖抑制作用以及对DNA合成的影响。暴露6 h、9 h和12 h后，所有人白血病细胞系的活力均未受到哌plartine的影响，而暴露24 h后观察到稳定下降。如通过孵育24小时后5-溴-2 '-脱氧尿苷（BrdU）掺入的减少所揭示的，piplartine的抗增殖活性似乎与DNA合成的抑制有关。当浓度为10 μ g/ml时，哌嗪介导的细胞数量减少与死亡细胞数量增加相关。这些发现得到了形态学分析的证实。然而，在最低浓度（2.5 μ g/ml），piplartine处理的细胞表现出典型的凋亡形态学变化。在匹拉丁处理的细胞（2.5 μ g/ml）的裂解物中也观察到半胱天冬酶-3活性的增加。我们的研究结果表明，piplartine可以抑制白血病生长，减少细胞存活，触发细胞凋亡和/或坏死，这取决于使用的浓度。(c)2006爱思唯尔有限公司保留所有权利。
Piplartine {5,6-dihydro-1-[1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-2(1H)pyridinone} is an alkaloid/amide component of Piper species. The purpose of the present study was to examine the antiproliferative effects of piplartine on human leukemia cell lines HL-60, K562, Jukart, and Molt-4 using the trypan blue exclusion method, as well as the effect of piplartine on DNA synthesis. The viability of all human leukemia cell lines were not affected by piplartine after 6 h, 9 h, and 12 h exposure, whereas a steady decline was seen after an exposure time of 24 h. The antiproliferative activity of piplartine seemed to be related to the inhibition of DNA synthesis, as revealed by the reduction of 5-bromo-2'-deoxyuridine (BrdU) incorporation after 24 h of incubation. Piplartine-mediated reduction in cell number was associated with an increasing number of dead cells at a concentration of 10 mu g/ml. These findings were corroborated by morphologic analysis. However, at the lowest concentration (2.5 mu g/ml), piplartine-treated cells exhibited typical apoptotic morphological changes. The increase in caspase-3 activity was also observed in lysates of piplartine-treated cells (2.5 mu g/ml). Our findings suggest that piplartine can suppress leukemia growth and reduce cell survival, triggering both apoptosis and/or necrosis, depending on the concentration used. (c) 2006 Elsevier Ltd. All rights reserved.