Vargo Melissa A, Voss Oliver H, Poustka Frantisek, Cardounel Arturo J, Grotewold Erich, Doseff Andrea I
Pulmonary and Critical Care, USA.
Biochem Pharmacol. 2006 Sep 14;72(6):681-92. doi: 10.1016/j.bcp.2006.06.010. Epub 2006 Jul 17.
Apigenin, a flavone abundantly found in fruits and vegetables, exhibits antiproliferative, anti-inflammatory, and antimetastatic activities through poorly defined mechanisms. In the present study, the treatment of different cell lines with apigenin resulted in selective antiproliferative and apoptotic effect in monocytic and lymphocytic leukemias. Apigenin-induced-apoptosis was mediated by the activation of caspase-9 and caspase-3. Apigenin was found intracellularly and localized to the mitochondria. Treatment of monocytic cells with apigenin was accompanied by an increase in reactive oxygen species (ROS) and phosphorylation of the MAPKs, p38 and ERK. However, the inhibition of ROS, p38 or ERK failed to block apoptosis, suggesting that these cellular responses induced by apigenin are not essential for the induction of apoptosis. In addition, apigenin induced the activation of PKCdelta. Pharmacological inhibition of PKCdelta, the expression of dominant-negative PKCdelta and silencing of PKCdelta in leukemia cells showed that apigenin-induced-apoptosis requires PKCdelta activity. Together, these results indicate that this flavonoid provides selective activity to promote caspase-dependent-apoptosis of leukemia cells and uncover an essential role of PKCdelta during the induction of apoptosis by apigenin.
芹菜素是一种在水果和蔬菜中大量存在的黄酮类化合物，其通过尚不明确的机制表现出抗增殖、抗炎和抗转移活性。在本研究中，用芹菜素处理不同细胞系可导致单核细胞性和淋巴细胞性白血病出现选择性抗增殖和凋亡效应。芹菜素诱导的凋亡由半胱天冬酶 -9 和半胱天冬酶 -3 的激活介导。芹菜素在细胞内被发现并定位于线粒体。用芹菜素处理单核细胞会伴随着活性氧（ROS）增加以及丝裂原活化蛋白激酶（MAPKs）p38 和细胞外信号调节激酶（ERK）的磷酸化。然而，抑制 ROS、p38 或 ERK 未能阻断凋亡，这表明芹菜素诱导的这些细胞反应对于凋亡诱导并非必不可少。此外，芹菜素诱导了蛋白激酶 Cδ（PKCδ）的激活。在白血病细胞中对 PKCδ 进行药理抑制、表达显性负性 PKCδ 以及使 PKCδ 沉默表明，芹菜素诱导的凋亡需要 PKCδ 活性。总之，这些结果表明这种黄酮类化合物具有选择性活性以促进白血病细胞的半胱天冬酶依赖性凋亡，并揭示了 PKCδ 在芹菜素诱导凋亡过程中的重要作用。
