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Sinomenine hydrochloride sensitizes cervical cancer cells to ionizing radiation by impairing DNA damage response

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-inflammat...

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Autores principales: Zhang, Dan, Dong, Yiping, Zhao, Ying, Zhou, Congya, Qian, Yuanjie, Hegde, Muralidhar L., Wang, Haibo, Han, Suxia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151895/
https://www.ncbi.nlm.nih.gov/pubmed/30226618
http://dx.doi.org/10.3892/or.2018.6693
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author Zhang, Dan
Dong, Yiping
Zhao, Ying
Zhou, Congya
Qian, Yuanjie
Hegde, Muralidhar L.
Wang, Haibo
Han, Suxia
author_facet Zhang, Dan
Dong, Yiping
Zhao, Ying
Zhou, Congya
Qian, Yuanjie
Hegde, Muralidhar L.
Wang, Haibo
Han, Suxia
author_sort Zhang, Dan
collection PubMed
description 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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spelling pubmed-61518952019-11-01 Sinomenine hydrochloride sensitizes cervical cancer cells to ionizing radiation by impairing DNA damage response Zhang, Dan Dong, Yiping Zhao, Ying Zhou, Congya Qian, Yuanjie Hegde, Muralidhar L. Wang, Haibo Han, Suxia Oncol Rep Articles 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. D.A. Spandidos 2018-11 2018-09-10 /pmc/articles/PMC6151895/ /pubmed/30226618 http://dx.doi.org/10.3892/or.2018.6693 Text en Copyright © 2018, Spandidos Publications
spellingShingle Articles
Zhang, Dan
Dong, Yiping
Zhao, Ying
Zhou, Congya
Qian, Yuanjie
Hegde, Muralidhar L.
Wang, Haibo
Han, Suxia
Sinomenine hydrochloride sensitizes cervical cancer cells to ionizing radiation by impairing DNA damage response
title Sinomenine hydrochloride sensitizes cervical cancer cells to ionizing radiation by impairing DNA damage response
title_full Sinomenine hydrochloride sensitizes cervical cancer cells to ionizing radiation by impairing DNA damage response
title_fullStr Sinomenine hydrochloride sensitizes cervical cancer cells to ionizing radiation by impairing DNA damage response
title_full_unstemmed Sinomenine hydrochloride sensitizes cervical cancer cells to ionizing radiation by impairing DNA damage response
title_short Sinomenine hydrochloride sensitizes cervical cancer cells to ionizing radiation by impairing DNA damage response
title_sort sinomenine hydrochloride sensitizes cervical cancer cells to ionizing radiation by impairing dna damage response
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151895/
https://www.ncbi.nlm.nih.gov/pubmed/30226618
http://dx.doi.org/10.3892/or.2018.6693
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