Dihydromyricetin prevents cardiotoxicity and enhances anticancer activity induced by adriamycin.
Dihydromyricetin prevents cardiotoxicity and enhances anticancer activity induced by adriamycin.
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二氢杨梅素可预防心脏毒性并增强阿霉素诱导的抗癌活性
DOI：
10.18632/oncotarget.2410
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发表时间：
2015-02-20
期刊：
影响因子：
--
通讯作者：
He Q
中科院分区：
文献类型：
--
作者：
Zhu H;Luo P;Fu Y;Wang J;Dai J;Shao J;Yang X;Chang L;Weng Q;Yang B;He Q
阿霉素是一种广泛应用于多种化疗方案的蒽环类抗生素，但其心脏毒性一直受到挑战，在最严重的情况下会导致致命的充血性心力衰竭。本研究表明，从显齿蛇葡萄中提取的天然产物二氢杨梅素对阿霉素致ICR小鼠心肌损伤具有保护作用。二氢杨梅素可降低小鼠血清中ALT、LDH和CKMB水平，从而显著减少阿霉素引起的中毒性死亡。保护作用也表明，在原代心肌细胞的异常心电图变化，消除增殖停滞和凋亡细胞死亡的缓解。进一步的研究表明，二氢杨梅素挽救了阿霉素引起的抗凋亡蛋白ARC的丢失，参与了心脏保护作用。有趣的是，阿霉素与二氢杨梅素联合使用时，阿霉素的抗癌活性没有受到损害，这通过阿霉素加二氢杨梅素在人白血病U937细胞和异种移植模型中以p53依赖性方式实现的增强的抗癌作用来证明。这些结果共同保证了二氢杨梅素作为阿霉素的合理心脏保护剂的潜在价值，通过保护心肌细胞免于凋亡，同时增强阿霉素的抗癌活性，从而进一步增加后者的治疗窗口。
Adriamycin, a widely used anthracycline antibiotic in multiple chemotherapy regimens, has been challenged by the cardiotoxicity leading to fatal congestive heart failure in the worst condition. The present study demonstrated that Dihydromyricetin, a natural product extracted from ampelopsis grossedentat, exerted cardioprotective effect against the injury in Adriamycin-administrated ICR mice. Dihydromyricetin decreased ALT, LDH and CKMB levels in mice serum, causing a significant reduction in the toxic death triggered by Adriamycin. The protective effects were also indicated by the alleviation of abnormal electrocardiographic changes, the abrogation of proliferation arrest and apoptotic cell death in primary myocardial cells. Further study revealed that Dihydromyricetin-rescued loss of anti-apoptosis protein ARC provoked by Adriamycin was involved in the cardioprotection. Intriguingly, the anticancer activity of Adriamycin was not compromised upon the combination with Dihydromyricetin, as demonstrated by the enhanced anticancer effect achieved by Adriamycin plus Dihydromyricetin in human leukemia U937 cells and xenograft models, in a p53-dependent manner. These results collectively promised the potential value of Dihydromyricetin as a rational cardioprotective agent of Adriamycin, by protecting myocardial cells from apoptosis, while potentiating anticancer activities of Adriamycin, thus further increasing the therapeutic window of the latter one.
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影响因子：
2
作者：
Hase, K;Ohsugi, M;Namba, T
通讯作者：
Namba, T
影响因子：
105.7
作者：
BONADONNA, G;MONFARDINI, S;FOSSATIB.F
通讯作者：
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影响因子：
7.4
作者：
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通讯作者：
Wu, X
影响因子：
7.7
作者：
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通讯作者：
Kitsis RN
影响因子：
3.2
作者：
Hasinoff, Brian B.;Herman, Eugene H.
通讯作者：
Herman, Eugene H.