Abstract
BackgroundCisplatin (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.MethodsBioactivities 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.ResultsOur 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 combined treatment exerted cytotoxicity by inducing G2/M arrest and apoptosis. RA in combined with CDDP significantly inhibiting the expression of p-FAK (Tyr 925) in RCC 786-O cells in vitro.ConclusionWe 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 combined treatments may be effective strategies for intervention of RCC 786-O cell activity.
Highlights
Cisplatin (CDDP) is a chemotherapeutic drug which causes adverse side effects
Inhibitory effects of HWG, rosmarinic acid (RA) and CDDP on the growth of HK‐2 and 786‐O cells To study the effects of HWG, RA and CDDP on the proliferation of HK-2 cells, 786-O cells were exposed to different concentrations of HWG, RA and CDDP for 48 h and monitored using the MTT assay
Our study demonstrated that CDDP dose-dependently inhibits 786-O cell and HK-2 cells proliferation
Summary
Cisplatin (CDDP) is a chemotherapeutic drug which causes adverse side effects. Glechoma hederacea is a traditional Chinese herb belonging to the Labiatae family and has many biological activities. 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. Clear cell RCC (ccRCC) is the most common subtype of renal cancer and accounts for approximately 70–75% of cases, so it cannot be assumed that all RCC derived cell lines represent ccRCC [3,4,5]. Phytochemicals are naturally occurring plant-based compounds that can augment the anti-cancer activity of CDDP, with minimal side effects. Combination therapy, which is a treatment modality combining two or more therapeutic agents is a cornerstone in cancer therapy and has provided highly effective results [9,10,11,12]
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