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Selective Killing of Cancer Cells by Nonplanar Aromatic Hydrocarbon‐Induced DNA Damage
Advanced Science ( IF 14.3 ) Pub Date : 2019-09-16 , DOI: 10.1002/advs.201901341
Yan Zhou 1, 2 , Fuwei Gan 3 , Yuanliang Zhang 4 , Xiaozhen He 1, 2 , Chengshuo Shen 3 , Huibin Qiu 3 , Peifeng Liu 1, 2
Advanced Science ( IF 14.3 ) Pub Date : 2019-09-16 , DOI: 10.1002/advs.201901341
Yan Zhou 1, 2 , Fuwei Gan 3 , Yuanliang Zhang 4 , Xiaozhen He 1, 2 , Chengshuo Shen 3 , Huibin Qiu 3 , Peifeng Liu 1, 2
Affiliation
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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.
中文翻译：
非平面芳香烃诱导的 DNA 损伤选择性杀死癌细胞
目前大量的化疗药物通过抑制癌细胞的DNA合成来阻止肿瘤的生长。最近发现，许多以前被认为具有致癌性的平面多环芳烃（PAHs）衍生物，通过DNA交联表现出抗癌活性。然而，这些多环芳烃的实际应用因其对大多数肿瘤的低治疗效率和选择性而受到极大限制。在此，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，它对肝癌、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 可有效抑制肝癌小鼠的肿瘤生长，并且对正常小鼠几乎没有副作用。 RNA测序和验证结果表明，[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细胞凋亡增加。这项研究揭示了PAHs在选择性杀死肿瘤细胞方面的意想不到的作用和分子机制，并为精准癌症治疗提供了有效策略。
更新日期：2019-09-16
中文翻译：
非平面芳香烃诱导的 DNA 损伤选择性杀死癌细胞
目前大量的化疗药物通过抑制癌细胞的DNA合成来阻止肿瘤的生长。最近发现，许多以前被认为具有致癌性的平面多环芳烃（PAHs）衍生物，通过DNA交联表现出抗癌活性。然而，这些多环芳烃的实际应用因其对大多数肿瘤的低治疗效率和选择性而受到极大限制。在此，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，它对肝癌、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 可有效抑制肝癌小鼠的肿瘤生长，并且对正常小鼠几乎没有副作用。 RNA测序和验证结果表明，[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细胞凋亡增加。这项研究揭示了PAHs在选择性杀死肿瘤细胞方面的意想不到的作用和分子机制，并为精准癌症治疗提供了有效策略。
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