Selective Killing of Cancer Cells by Nonplanar Aromatic Hydrocarbon-Induced DNA Damage
Selective Killing of Cancer Cells by Nonplanar Aromatic Hydrocarbon-Induced DNA Damage
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非平面芳香烃诱导的 DNA 损伤选择性杀死癌细胞
DOI：
10.1002/advs.201901341
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发表时间：
2019
期刊：
影响因子：
15.1
通讯作者：
Liu Peifeng
中科院分区：
文献类型：
--
作者：
Zhou Yan;Gan Fuwei;Zhang Yuanliang;He Xiaozhen;Shen Chengshuo;Qiu Huibin;Liu Peifeng
目前大量的化学治疗剂通过抑制癌细胞的DNA合成来防止肿瘤的生长。最近发现，许多平面多环芳烃（PAH）衍生物，以前被称为致癌物，通过DNA交联显示抗癌活性。然而，这些多环芳烃的实际应用受到其对大多数肿瘤的低治疗效率和选择性的限制。本文报道了一种名为[4]helicenium的非平面PAH的抗癌特性，与正常细胞相比，它对肝、肺癌和白血病细胞表现出高度选择性的细胞毒性。此外，[4]helicenium有效抑制肝癌荷瘤小鼠的肿瘤生长，在正常小鼠中几乎没有副作用。RNA测序和确证结果表明[4]helicenium在肿瘤细胞中比在正常细胞中诱导更多的DNA损伤，导致肿瘤细胞周期停滞和凋亡增加。这项研究揭示了多环芳烃在选择性杀伤肿瘤细胞中的一个意想不到的作用和分子机制，并为精确的癌症治疗提供了一个有效的策略。
A large number of current chemotherapeutic agents prevent the growth of tumors by inhibiting DNA synthesis of cancer cells. It has been found recently that many planar polycyclic aromatic hydrocarbons (PAHs) derivatives, previously known as carcinogenic, display anticancer activity through DNA cross‐linking. However, the practical use of these PAHs is substantially limited by their low therapeutic efficiency and selectivity toward most tumors. Herein, the anticancer property of a nonplanar PAH named [4]helicenium, which exhibits highly selective cytotoxicity toward liver, lung cancer, and leukemia cells compared with normal cells, is reported. Moreover, [4]helicenium effectively inhibits tumor growth in liver cancer‐bearing mice and shows little side effects in normal mice. RNA sequencing and confirmatory results demonstrate that [4]helicenium induces more DNA damage in tumor cells than in normal cells, resulting in tumor cell cycle arrest and apoptosis increment. This study reveals an unexpected role and molecular mechanism for PAHs in selectively killing tumor cells and provides an effective strategy for precision cancer therapies.