Anticancer Effects of Salvia miltiorrhiza Alcohol Extract on Oral Squamous Carcinoma Cells

Abstract

Researchers have reported significant effects from Danshen (Salvia miltiorrhiza) in terms of inhibiting tumor cell proliferation and promoting apoptosis in breast cancer, hepatocellular carcinomas, promyelocytic leukemia, and clear cell ovary carcinomas. Here we report our data indicating that Danshen extracts, especially alcohol extract, significantly inhibited the proliferation of the human oral squamous carcinoma (OSCC) cell lines HSC-3 and OC-2. We also observed that Danshen alcohol extract activated the caspase-3 apoptosis executor by impeding members of the inhibitor of apoptosis (IAP) family, but not by regulating the Bcl-2-triggered mitochondrial pathway in OSCC cells. Our data also indicate that the extract exerted promising effects in vivo, with HSC-3 tumor xenograft growth being suppressed by 40% and 69% following treatment with Danshen alcohol extract at 50 and 100 mg/kg, respectively, for 34 days. Combined, our results indicate appreciable anticancer activity and significant potential for Danshen alcohol extract as a natural antioxidant and herbal human oral cancer chemopreventive drug.

Overview of Salvia miltiorrhiza as a Potential Therapeutic Agent for Various Diseases: An Update on Efficacy and Mechanisms of Action

“…Among them, some studies offered conflicting results regarding the mechanism by which S. miltiorrhiza extract induced apoptosis. For example, 95% ethanol extract of S. miltiorrhiza at doses between 10–50 µg/mL for 48 or 72 h induced apoptosis in OSCC cell lines, by down-regulating the expression of XIAP and survivin, two members of the inhibitor of apoptosis protein (IAP) family; however, treatment with S. miltiorrhiza extract did not change the levels of antiapoptotic proteins Bcl-2 and Bcl-xL and the proapoptotic proteins Bax and Bad, as well as apoptosis-related mitochondrial membrane potential [ 36 ]. In contrast, treatment with methanol extract of S. miltiorrhiza at doses between 10–40 µg/mL for 24 h decreased the expression of Bcl-2 and Bcl-xl and increased the expression of Bax in Glc-82 cells; in addition, treatment with 20 and 40 µg/mL of S. miltiorrhiza extract increased the levels of cleaved caspase-9, caspase-3, and PARP1, suggesting the possibility of the involvement of the mitochondrial apoptotic pathway in S. miltiorrhiza extract-mediated cytotoxicity [ 34 ].…”

“…In the H460 xenograft model, subcutaneous injection of PROS down-regulated STAT3 and VEGF expression and caspase-3 activation. In Wang et al’s study, either double-distilled water (ddH2O), 95% ethanol, or 1:1 water/ethanol extract of S. miltiorrhiza was added to two human oral squamous cell carcinoma (OSCC) cell lines, HSC-3 and OC-2, and it turned out that 95% ethanol extract of S. miltiorrhiza showed the greatest antioxidant and radical scavenging capabilities [ 36 ]. After treatment of HSC-3 cells with S. miltiorrhiza alcohol extract at doses of 10, 25, or 50 µg/mL for 48 or 72 h, significant decreases in the expression of X-linked inhibitor of apoptosis protein (XIAP) and survivin were observed but there were no changes in the levels of mitochondrial membrane potential (ΔΨm), antiapoptotic proteins (Bcl-2 and Bcl-xL), and proapoptotic proteins (Bax and Bcl-2 associated agonist of cell death [Bad]).…”

Pristimerin induces apoptosis of oral squamous cell carcinoma cells via G1 phase arrest and MAPK/Erk1/2 and Akt signaling inhibition

“…Most anticancer drugs mediate their effects via cell apoptosis induction, which is the major mechanism involved in the treatment of cancer, including oral cancer (28). Apoptosis can be initiated either by the mitochondria (the intrinsic pathway) or through cell death receptors (the extrinsic pathway), leading to the activation of caspase cascades and resulting in apoptosis.…”

Health-Promoting Effects of Thymus Phenolic-Rich Extracts: Antioxidant, Anti-inflammatory and Antitumoral Properties

“…It is known that apoptosis can be induced by activation of the caspase cascade through death receptors pathway or the mitochondrial death signaling, whose members are either proapoptotic (Bax, Bad) or antiapoptotic (Bcl-2, Bcl-XL) [ 27 , 28 , 29 ]. Therefore, the induction of programed cell death in cancer cells is one of the strategies used in the development of anti-cancer drugs [ 24 , 30 , 31 , 32 ] and, in particular, plants used in traditional forms have been the focus of attention as plant-based foods, whose regular consumption may be correlated with a lower incidence of cancer [ 33 , 34 , 35 , 36 ].…”