Background: Cisplatin (CDDP) is a chemotherapeutic drug which also causes adverse side effects.Glechoma hederacea is a traditional Chinese herb belonging to the Labiatae family and has many biological activities. Our previous study indicated that rosmarinic acid (RA) was the most abundant phytochemical in G. hederacea. However, the antioxidant or anti-inflammatory effects of the combined treatment of G. hederacea, RA and CDDP on human renal cell carcinoma (RCC) 786-O cells have not been clearly demonstrated. We aimed to investigate the bioefficacy of hot water extracts of G. hederacea (HWG) and RA in inhibiting RCC 786-O cell activity and its synergism with CDDP against metastatic renal cancer cell. Methods:Bioactivities of the combination treatment of HWG, RA, HWG/CDDP and RA/CDDP were assessed using the MTT assay and transwell migration, and the crude extract/compound efficacy was evaluated using wound healing migration assays, flow cytometry and western blotting. Results: Our study indicates that CDDP inhibits 786-O cell proliferation and migration and HWG and RA protect against these effects. On the other hand, HWG and RA demonstrate a low cytotoxic effect in human renal proximal tubular epithelial cell line -2 (HK-2 cells). Cell cycle analysis found that HWG/CDDP and RA/CDDP combination treatment exerted cytotoxicity by inducing G2/M arrest and apoptosis. RA in combination with CDDP significantly inhibit the expression of p-FAK (Tyr 925) in RCC 786-O cells in vitro. Conclusion: We propose that the inhibition of RA on RCC 786-O cell invasion and migration may partly occur through the downregulation of FAK phosphorylation. The HWG/CDDP and RA/CDDP combination treatments may be effective strategies for intervention of RCC 786-O cell activity. BackgroundRenal cell carcinoma (RCC) is the most common type of kidney malignancy and accounts for ~ 3% of tumors in adults. However, only 2% RCC cases are associated with inherited gene mutations. It is also associated with a high metastatic potential [1,2]. RCC is the most lethal genitourinary cancer and patients with metastatic RCC have poor overall survival profiles [3]. 7075% renal cancers are clear cell carcinomas, which have traditionally been resistant to chemo-or radiotherapy [4]. One of the
Background Glechoma hederacea belongs to the Labiatae family and has many biological effects. Our previously in vitro studies, hot water extract of G. hederacea (HWG) possessed antioxidant and anti-inflammatory activities. Also, the Ames test indicated that HWG had no mutagenicity. However, the in vivo toxicity and antioxidant capacity have not been clearly demonstrated. Thus, this study was aimed to evaluate the antioxidant properties and the safety level of HWG by using animal models. Methods The genotoxicity were performed by micronucleus assays in mice. Acute oral toxicity and 28-day repeated feeding toxicity tests were performed via the oral gavage method for Sprague-Dawley (SD) rats. Furthermore, the effect of HWG on the oxidation–antioxidation equilibrium of male rats was also evaluated. Results HWG did not induce an increase in micronucleus ratios in vivo, no acute lethal effect at a maximum tested dose of 5.0 g HWG /kg bw was observed in rats. The 28-day oral toxicity study revealed the no observed adverse effect level (NOAEL) of HWG in rats was 1.0 g/kg bw. The HWG-treatment significantly elevated the vitamin C level and the SOD activity in heart, and increased the vitamin E concentrations in brain. The HWG-treatment maintained the balance of the glutathione level and the activities of catalase and glutathione peroxidase. Besides, the level of lipid peroxidation and plasma of total antioxidant status (TAS) showed that HWG-treated rats were not significantly changed compared with the control group. Conclusions HWG had no genotoxicity, and did not induce acute or subacute toxicity in SD rat. The level of no observed adverse effect level (NOAEL) of HWG rats was 1.0 g/kg bw for subacute toxicity study. HWG possessed antioxidant potential and reduced oxidative stress by improving the antioxidant system in animal.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.