Abstract
Objective: To explore whether Rhaponticum uniflorum (R. uniflorum) had anti-tumor effects in oral cancer and investigate the molecular mechanisms involved in these anti-tumor effects.Methods: Chemical compositions of R. uniflorum ethyl acetate (RUEA) extracts were detected by ultra-performance liquid chromatography-Q/time-of-flight mass spectrometry (UPLC-Q/TOF-MS), followed by pharmacology-based network prediction analysis. The effects of RUEA extracts on proliferation, apoptosis, migration, and invasion ability of human oral squamous cell carcinoma (OSCC) cell line SCC15 were evaluated by CCK8 assay, Annexin V- fluorescein isothiocyanate/propidium iodide staining, wound healing assay, and Matrigel invasion assay, respectively. The mRNA and protein expression of peroxiredoxin1 (Prx1), the epithelial-to-mesenchymal transition (EMT) marker E-cadherin, vimentin, and Snail were determined by quantitative real-time reverse transcription polymerase chain reaction and western blotting. A mouse xenograft model of SCC15 cells was established to further evaluate the effect of RUEA extracts in vivo. Immunohistochemical assessment of Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling staining of apoptotic cells were performed on the tumor tissues to assess the effects of RUEA extracts on proliferation and apoptosis.Results: Fourteen compounds were identified from RUEA extracts by UPLC-Q/TOF-MS. The pharmacology-based network prediction analysis showed that Prx1 could be a potential binder of RUEA extracts. In SCC15 cells, RUEA extracts inhibited cell viability, induced apoptosis, and suppressed cell invasion and migration in a concentration-dependent manner. After treatment with RUEA extracts, the mRNA and protein expression of E-cadherin increased, whereas those of Prx1, vimentin, and Snail decreased. RUEA extracts also affected the EMT program and suppressed cell invasion and migration in Prx1 knockdown SCC15 cells. In an OSCC mouse xenograft model, RUEA extracts (25 and 250 mg/kg) significantly inhibited the growth of tumors. Compared with the control group, Ki67 expression was reduced and apoptosis rates were elevated in the transplanted tumors treated with RUEA extracts. RUEA extracts increased the expression of E-cadherin and decreased the expression of Prx1, vimentin, and Snail in vivo.Conclusion: RUEA extracts inhibited tumor growth and invasion by reducing Prx1 expression and suppressing the EMT process in OSCC. RUEA extracts may be a potential candidate for OSCC treatment.
Highlights
Oral cancer is one of the most common cancers, with more than 560,000 new cases and 300,000 deaths reported worldwide annually (Siegel et al, 2014)
The original specimen was deposited for future use, and the R. uniflorum ethyl acetate (RUEA) extracts were dissolved in dimethyl sulfoxide (DMSO) and diluted to obtain two different storage concentrations (50 μg/mL and 50 mg/mL)
Yan et al (2013) showed that RUWEs enhanced the total antioxidant capacity, increased scavenging activity of free hydroxyl radicals, and regulated superoxide dismutase activity. These findings suggest that RUEA extracts may inhibit tumor growth and induce apoptosis by modulating oxidative stress in Oral squamous cell carcinoma (OSCC)
Summary
Oral cancer is one of the most common cancers, with more than 560,000 new cases and 300,000 deaths reported worldwide annually (Siegel et al, 2014). The 5-year survival rate for head and neck cancer remains consistent at around 50%. Oral squamous cell carcinoma (OSCC) accounts for almost 95% of all head and neck cancers and can develop from oral precancerous lesions, such as leukoplakia and lichen planus (Warnakulasuriya, 2010). Accumulating evidence has suggested that natural plants used in traditional Chinese medicine (TCM) have outstanding advantages such as efficiency, hypotoxicity, sufficiency, and beneficial effects on the treatment of cancers in clinical practice in China and other countries (Shu et al, 2005). Compared with isolated compounds from natural plants, research suggests that complex containing many active phytochemical components in TCM have unique advantages.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
