Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells

Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 07/2010; 398(1):62-7. DOI: 10.1016/j.bbrc.2010.06.033
Source: PubMed


Recently, salidroside (p-hydroxyphenethyl-beta-d-glucoside) has been identified as one of the most potent compounds isolated from plants of the Rhodiola genus used widely in traditional Chinese medicine, but pharmacokinetic data on the compound are unavailable. We were the first to report the cytotoxic effects of salidroside on cancer cell lines derived from different tissues, and we found that human breast cancer MDA-MB-231 cells (estrogen receptor negative) were sensitive to the inhibitory action of low-concentration salidroside. To further investigate the cytotoxic effects of salidroside on breast cancer cells and reveal possible ER-related differences in response to salidroside, we used MDA-MB-231 cells and MCF-7 cells (estrogen receptor-positive) as models to study possible molecular mechanisms; we evaluated the effects of salidroside on cell growth characteristics, such as proliferation, cell cycle duration, and apoptosis, and on the expression of apoptosis-related molecules. Our results demonstrated for the first time that salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells and may be a promising candidate for breast cancer treatment.

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Available from: Xiaolan Hu, Nov 25, 2014
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    • "It has been hypothesized that salidroside may alleviate mitochondrial-generated ROS and manipulate mitochondrial-related apoptosis in a variety of cells (10). Moreover, salidroside has been found to exert an antiproliferation effect on a number of various cancer cells (11,12), and induce cell-cycle arrest and apoptosis in breast cancer (13). "
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    ABSTRACT: Oxidative stress is important in carcinogenesis and metastasis. Salidroside, a phenylpropanoid glycoside isolated from Rhodiola rosea L., shows potent antioxidant properties. The aim of the present study was to investigate the roles of salidroside in cell proliferation, the cell cycle, apoptosis, invasion and epithelial‑mesenchymal transition (EMT) in A549 cells. The human alveolar adenocarcinoma cell line, A549, was incubated with various concentrations of salidroside (0, 1, 5, 10 and 20 µg/ml) and cell proliferation was detected by 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay. Propidium iodide (PI) staining was used to determine the cell cycle by flow cytometry. Cell apoptosis was detected by Annexin V‑fluorescein isothiocyanate and PI double‑staining, and tumor invasion was detected by Boyden chamber invasion assay. Western blot analysis was performed to detect the expression of EMT markers, Snail and phospho‑p38. The results showed that salidroside significantly reduced the proliferation of A549 cells, inhibited cell cycle arrest in the G0/G1 phase and induced apoptosis. Salidroside inhibited transforming growth factor‑β‑induced tumor invasion and suppressed the protein expression of Snail. As an antioxidant, salidroside inhibited the intracellular reactive oxygen species (ROS) formation in a dose‑dependent manner in A549 cells, and depletion of intracellular ROS by vitamin C suppressed apoptosis by salidroside treatment. Salidroside was also found to inhibit the expression of phospho‑p38 in A549 cells. In conclusion, salidroside inhibits cell proliferation, the cell cycle and metastasis and induces apoptosis, which may be due to its interference in the intracellular ROS generation, thereby, downregulating the ROS‑phospho‑p38 signaling pathway.
    Oncology letters 04/2014; 7(4):1159-1164. DOI:10.3892/ol.2014.1863 · 1.55 Impact Factor
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    • "It has exhibited a wide range of pharmacological properties, including anti-aging, anti-oxidation, anti-inflammatory, anti-fatigue, anti-depressant activities, antiviral effects, hepatoprotective, neuroprotective, and cardiovascular protective characteristics (Zhang et al., 2007, 2010; Wang et al., 2009). Recent studies have also shown that salidroside may prevent the growth of leukemia, stomach adenocarcinoma and parotid carcinoma (Hu et al., 2010), and may also significantly decrease neovascular reactions (De Bock et al., 2004). Despite its attractive pharmacological activities, the therapeutic potential of salidroside has been significantly restricted by its short biological half-life and poor oral bioavailability (Fan et al., 2007). "
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    ABSTRACT: A novel pH-responsive nano-carrier MSNs-PAA, possessing mesoporous silica nanoparticles (MSNs) cores and poly(acrylic acid) (PAA) shell-layers, was developed for controlled release of salidroside. The vinyl double bonds modified MSNs were synthesized by using cetyltrimethylammonium bromide (CTAB) as templates, tetraethyl orthosilicate (TEOS) as silicon source, and 3-(trimethoxylsilyl) propyl methacrylate (MPS) as surface modification functionalities. The pH-responsive layers of PAA were grafted onto the vinyl double bonds of the MSNs via precipitation polymerization, producing the MSNs-PAA with a hollow cubic core and mesoporous shell with penetrating pore channels. The characteristic results also showed that PAA was successfully grafted onto the surface of the MSNs. The MSNs-PAA was investigated as carriers for loading and regulating the release of salidroside in different pH solutions for the first time. The results demonstrated that the PAA layers on the surface of MSNs-PAA exhibited opened and closed states at different pH values, and thus could regulate the uptake and release of salidroside. The application of such pH-responsive nano-carrier might offer a potential platform for controlled delivery and increasing the bioavailability of drugs.
    International Journal of Pharmaceutics 02/2013; 446(1-2). DOI:10.1016/j.ijpharm.2013.01.071 · 3.65 Impact Factor
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    • "Recent studies have shown that salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells and may be a promising candidate for breast cancer treatment.[19] In a further study, we will focus on investigating (i) the uncertain effect of the salidroside-epirubicin compound; and (ii) the dose-related pharmacologic and probable toxicologic effects of salidroside. "
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    ABSTRACT: Salidroside [2-(4-hydroxyphenyl)ethyl-β-D-glucopyranoside], one of the most potent ingredients extracted from the plant Rhodiola rosea L., has been shown to have a cardiovascular protective effect as an antioxidant, and early treatment of epirubicin-induced cardiotoxicity has been the focus of clinical chemotherapy in patients with breast cancer. However, the cardioprotective effects of salidroside on epirubicin-induced cardiotoxicity, especially early left ventricular regional systolic dysfunction, have to date been sparsely investigated. The aim of this study was to investigate the protective effects of salidroside in preventing early left ventricular regional systolic dysfunction induced by epirubicin. Sixty patients with histologically confirmed breast cancer were enrolled. Eligible patients were randomized to receive salidroside (600 mg/day; n = 30) or placebo (n = 30) starting 1 week before chemotherapy. Patients were investigated by means of echocardiography and strain rate (SR) imaging. We also measured plasma concentrations of reactive oxygen species (ROS). All parameters were assessed at baseline and 7 days after each new epirubicin dose of 100 mg/m2. A decline of the SR peak was observed at an epirubicin dose of 200 mg/m2, with no significant differences between salidroside and placebo (1.35 ± 0.36 vs 1.42 ± 0.49/second). At growing cumulative doses of epirubicin, the SR normalized only with salidroside, showing a significant difference in comparison with placebo at epirubicin doses of 300 mg/m2 (1.67 ± 0.43 vs 1.32 ± 0.53/second, p < 0.05) and 400 mg/m2 (1.68 ± 0.29 vs 1.40 ± 0.23/second, p < 0.05). Moreover, a significant increase in plasma concentrations of ROS was found with placebo, but they remained unchanged with salidroside. Salidroside can provide a protective effect on epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer.
    06/2012; 12(2):101-6. DOI:10.2165/11632530-000000000-00000
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