Diallyl disulfide enhances carbon ion beams-induced apoptotic cell death in cervical cancer cells through regulating Tap73/ΔNp73
Diallyl disulfide enhances carbon ion beams-induced apoptotic cell death in cervical cancer cells through regulating Tap73/ΔNp73
复制标题
二烯丙基二硫化物通过调节 Tap73/Delta Np73 增强碳离子束诱导的宫颈癌细胞凋亡
DOI：
10.1080/15384101.2015.1104438
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发表时间：
2015-12-02
期刊：
影响因子：
4.3
通讯作者：
Liu, Yuanyuan
中科院分区：
文献类型：
--
作者：
Di, Cuixia;Sun, Chao;Liu, Yuanyuan
二烯丙基二硫化物(DADS)是通过水蒸气蒸馏从粉碎的大蒜中提取的，据报道，它在几种癌症类型中具有抗癌活性。然而，DADS对高LET碳束诱导的细胞死亡的影响仍不清楚。因此，我们使用人宫颈癌细胞来阐明这种二烯丙基硫化物的分子效应。放射治疗仍是治疗的主要手段，特别是在晚期宫颈癌中，仍有提高放射敏感性以减少放射剂量的空间。在这项研究中，我们发现高LET碳束辐射效应的显著特征是抑制细胞活力、细胞周期停滞、凋亡细胞显著增加、转录因子p73的调节以及细胞凋亡途径的关键介质的改变。我们进一步证明，照射后的HeLa细胞经10MU的DADS处理后，细胞存活率下降，放射敏感性增加。此外，经DADS处理的细胞明显抑制辐射诱导的G2/M期停滞，但促进辐射诱导的细胞凋亡。此外，DADS和辐射通过上调促凋亡的Tap73和抗凋亡的Np73及其下游蛋白FASLG和APAF1的比例，加剧了细胞凋亡通路的激活。综上所述，这些结果表明DADS是一种潜在的宫颈癌放射增敏剂。
Diallyl disulfide (DADS), extracted from crushed garlic by steam-distillation, has been reported to provide the anticancer activity in severalcancertypes. However,the effect of DADS on high-LET carbon beams - induced cell death remains unknown. Therefore, we used human cervical cancer cells to elucidate the molecular effects ofthis dallylsulfide. Radiotherapy remains the mainstay of treatment, especially in advanced cervical cancer and there is still space to improve the radiosensitivity to reduce radiation dosage. In this study, we found that radiation effects evoked by high-LET carbon beam was marked by inhibition of cell viability, cell cycle arrest, significant rise of apoptotic cells, regulation of transcription factor, such as p73, as well as alterations of crucial mediator of theapoptosispathway. We further demonstratedthat pretreatment of 10 mu M DADS in HeLa cells exposed to radiation resulted in decrease in cell viability and increased radiosensitivity. Additionally, cells pretreated with DADS obviously inhibited the radiation-induced G2/M phase arrest, but promoted radiation-induced apoptosis. Moreover, combination DADS and the radiation exacerbated the activation of apoptosis pathways through up-regulated ration of pro-apoptotic Tap73 to anti-apoptotic Np73, and its downstream proteins, such as FASLG, and APAF1. Taken together, these results suggest thatDADS is a potentialcandidate as radio sensitive agent for cervical cancer.