Sinomenine hydrochloride sensitizes cervical cancer cells to ionizing radiation by impairing DNA damage response.
Sinomenine hydrochloride sensitizes cervical cancer cells to ionizing radiation by impairing DNA damage response.
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青藤碱盐酸盐通过损害 DNA 损伤反应使宫颈癌细胞对电离辐射敏感。
DOI：
10.3892/or.2018.6693
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发表时间：
2018-11
期刊：
影响因子：
4.2
通讯作者：
Han S
中科院分区：
文献类型：
--
作者：
Zhang D;Dong Y;Zhao Y;Zhou C;Qian Y;Hegde ML;Wang H;Han S
利用源自传统药物的植物化合物来改善人类疾病的势头一直在增强，因为它们具有高生物利用度和温和的副作用。青藤碱是一种从青风藤中提取的生物活性碱化合物，具有抗炎和抗肿瘤作用。然而，其抗肿瘤特性的分子机制尚未完全表征。本研究观察了水溶性青藤碱盐酸盐（SH）对人宫颈癌细胞株（HeLa）的放射增敏作用。SH通过促进电离辐射（IR）诱导的DNA双链断裂（DSB）的积累以及干扰DNA损伤检查点的激活而使HeLa细胞对IR敏感。然后我们研究了SH介导的细胞对IR增敏的分子机制，发现SH在转录水平抑制DNA损伤反应（DDR）因子Ku80和Rad51的表达。最后，在宫颈癌小鼠异种移植模型中证实了SH的放射增敏活性。与单纯IR相比，SH和IR联合治疗显著减缓了肿瘤的生长速度。总的来说，我们的研究不仅提供了分子的见解SH在细胞反应IR的新作用，但也表明了治疗潜力的SH作为一种放射增敏剂在宫颈癌治疗。
The use of plant-based compounds derived from traditional medicine to improve human diseases has been gaining momentum, due to their high bioavailability and moderate adverse effects. Sinomenine is one such biomonomer alkali compound derived from Sinomenium acutum and is known for its anti-inflammatory and antitumor effects. However, the molecular mechanism(s) of its antitumor properties are not fully characterized. In the present study, we evaluated the radiosensitizing effects of the water-soluble sinomenine, sinomenine hydrochloride (SH) in human cervical cancer cell line (HeLa). SH sensitized HeLa cells to ionizing radiation (IR) by promoting accumulation of IR-induced DNA double-strand breaks (DSBs) and also by interfering with DNA damage checkpoint activation. We then investigated the molecular mechanisms underlying the SH-mediated cellular sensitization to IR and found that SH inhibited the expression of DNA damage response (DDR) factors Ku80 and Rad51 at the transcription level. Finally, the radiosensitizing activity of SH was confirmed in a cervical cancer mouse xenograft model. The combinatorial treatment of SH and IR significantly slowed the tumor growth rate compared with IR alone. Collectively, our study not only provides molecular insights into the novel role of SH in cellular response to IR, but also suggests a therapeutic potential of SH as a radiosensitizer in cervical cancer therapy.
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影响因子：
6.2
作者：
Delaney, G;Jacob, S;Barton, M
通讯作者：
Barton, M
DOI：
10.1186/1478-811x-8-27
发表时间：
2010-09-22
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Freeman AK;Monteiro AN
通讯作者：
Monteiro AN
DOI：
10.1186/alzrt167
发表时间：
2013
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Kanungo J
通讯作者：
Kanungo J
影响因子：
3.8
作者：
Choi, Kyu-Sung;Kim, Ji Yeon;Lim, In Young
通讯作者：
Lim, In Young
影响因子：
4.8
作者：
Kitahara, O;Katagiri, T;Nakamura, Y
通讯作者：
Nakamura, Y