Journal
ONCOLOGY REPORTS
Volume 40, Issue 5, Pages 2886-2895Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2018.6693
Keywords
sinomenine hydrochloride; radiosensitizer; DNA damage response; DNA double-strand break repair; cancer therapy
Categories
Funding
- National Natural Science Foundation of China [81272488, 81472795, 81572968]
- NINDS-NIH [R01 NS088645]
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS088645] Funding Source: NIH RePORTER
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available