Salvianolic acid A shows selective cytotoxicity against multidrug-resistant MCF-7 breast cancer cells

Abstract

Multidrug resistance (MDR) is a major cause for incurable breast cancer. Salvianolic acid A (SAA), the hydrophilic polyphenolic derivative of Salvia miltiorrhiza Bunge (Danshen/Red Sage), was examined for cytotoxicities to MDR MCF-7 human breast cancer cells and their parental counterparts. We have shown that SAA inhibited proliferation, caused cell cycle arrest at the S phase, and induced apoptosis dose dependently to the two kinds of cancer cells. However, the resistant cells were significantly susceptible to the inhibition of SAA compared with the parental cells. SAA increased the level of reactive oxygen species (ROS) by 6.2-fold in the resistant cells, whereas the level of SAA-induced ROS changed only by 1.6-fold in their parental counterparts. Thus, the data showed that the selective cytotoxicity resulted from the hypersensitivity of the resistant cells to the strongly elevated ROS by SAA. In addition, SAA-triggered apoptosis was associated with increased caspase-3 activity, disrupted mitochondrial membrane potential, downregulated Bcl-2 expression, and upregulated Bax expression in the resistant cells. Moreover, SAA downregulated the level of P-glycoprotein, which was overexpressed in the resistant cells. This indicated that SAA modulated MDR. Furthermore, SAA showed higher antitumor activity than did doxorubicin in xenografts established from the resistant cells. The present work raised a possibility that SAA might be considered a potential choice to overcome MDR for the selective susceptibility of the resistant breast cancer cells to SAA treatment.

Salvianolic acid A reverses the paclitaxel resistance and inhibits the migration and invasion abilities of human breast cancer cells by inactivating transgelin 2

“…Based on these results, we conclude that transgelin 2 is vitally important for paclitaxel resistance and the migration and invasion abilities of human breast cancer cells.Recent studies have highlighted the key role of SAA in cancer therapy. For example, Wang et al31 found that SAA showed higher antitumor activity against multidrug-resistant breast cancer cells and enhanced the apoptosis of tumor cells. It was also revealed that SAA could decrease cell migration by modulating matrix metalloproteinase-9 32, 33 .…”

New insights into salvianolic acid A action: Regulation of the TXNIP/NLRP3 and TXNIP/ChREBP pathways ameliorates HFD-induced NAFLD in rats

“…Salvianolic acid A (SalA) is one of the most efficacious phenolic acids of seven water-soluble compounds isolated from the Radix Salvia miltiorrhiza 11 . Many studies have reported that SalA possesses a variety of pharmacological properties, including anti-oxidant, anti-inflammatory, anti-fibrotic and anti-carcinogenic activities 12 13 14 . Moreover, SalA demonstrated potent protective effects against hepatic fibrosis in high-fat diet (HFD)-fed type 2 diabetic rats, which was likely due to its anti-oxidative and anti-apoptotic properties 15 .…”

Protein arginine methyltransferase 1 may be involved in pregnane x receptor-activated overexpression of multidrug resistance 1 gene during acquired multidrug resistant

“…Interestingly, quercetin, which also has the same aglycone but not glycosylated, did not inhibit PRMT1. In addition, previous studies [ 46 , 47 ] reported that in vitro exposure to salvianolic acid A and naproxen decreased the expression and the efflux function of P-gp though the underling mechanism still unclear. Another study [ 48 ] reported that exposure to felodipline decrease the expression of BCRP, which is another PXR responsive gene.…”