Bidirect effects from cisplatin combine with rosmarinic acid (RA) or hot water extracts of Glechoma hederacea (HWG) on renal cancer cells

Abstract

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

Rosmarinic acid ameliorates renal interstitial fibrosis by inhibiting the phosphorylated-AKT mediated epithelial–mesenchymal transition in vitro and in vivo

“…It is a polyphenolic compound that can potentially be used at the pharmaceutical/nutritional interface. [14][15][16] Its chemical structure is shown in Fig. 1A.…”

“…15 Our previous study reveals that hot water extracts of Glechoma hederacea (HWG) and RA could afford protection against cisplatin-induced inhibition of 786-O cell proliferation and migration, with minimal toxicity in HK-2 human renal proximal tubular epithelial cells. 16 In a carbon tetrachloride (CCL4)-induced rat liver fibro-sis model, RA ameliorated the histopathological morphology, reduced the fibrosis grade, and decreased TGF-β1 and connective transforming growth factor expression levels in the fibrotic liver. 17 In this study, we used a UUO mouse model to identify the anti-renal fibrotic effects of RA.…”

The Antitumor Mechanism of the Polyphenol-enriched Ethyl Acetate Fraction Extract of Glechoma hederacea (Lamiaceae) against HepG2 Cells Involves Apoptosis Pathways

“…Flavonoids, plant polyphenolic compound derivatives of natural origin, have been shown to have a wide range of putative biological activities. Herb plantshave traditionally been used to prevent or treat various human diseases[ 9,14,37,38].…”