3-4-dihydroxyphenyllactic-acid and Lung-Neoplasms

Sodium Danshensu, extracted from the root of the Salvia miltiorrhiza, has pleiotropic effects including anti-oxidation, anti-inflammation and anti-tumor. However, whether Sodium Danshensu has an anti-cancer effect in lung cancer remains to be elucidated. The present study aimed to illustrate the effects of Sodium Danshensu on lung cancer cells and the potential molecular mechanisms. BEAS-2B, A549, and NCI-H1299 cells were stimulated with 25, 50, and 100 μM Sodium Danshensu for 24, 48, and 72 h, and then cell viability, apoptosis, migration and invasion were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry and Transwell assays, respectively. Moreover, the levels of Proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP9), B-cell lymphoma-2 (Bcl-2) associated X (Bax), Bcl-2, phosphorylated (p)-phosphoinositide 3-kinase (PI3K), and p-Protein kinase B (AKT) in lung cancer cells were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) and/or Western blot assays. We observed that Sodium Danshensu suppressed cells viability, migration, and invasion, as well as promoted cells apoptosis in A549 and NCI-H1299 cells in a dose-dependent manner, while Sodium Danshensu had no cytotoxic effect on the proliferation activity of BEAS-2B cells. Moreover, the expression of PCNA, MMP9, Bcl-2 were decreased, but Bax was up-regulated in Sodium Danshensu-treated A549 and NCI-H1299 cells. Our findings also revealed that Sodium Danshensu inhibited PI3K/AKT pathway in A549 and NCI-H1299 cells. In conclusion, our study provided the first evidence that Sodium Danshensu suppressed the malignant biological behaviors of lung cancer cells, indicating that Sodium Danshensu might be a latent candidate for lung cancer therapy.

Topics: A549 Cells; Apoptosis; Cell Movement; Cell Proliferation; Humans; Lactates; Lung Neoplasms; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Sodium

Increased survival of cancer cells mediated by high levels of ionizing radiation (IR) reduces the effectiveness of radiation therapy for non-small cell lung cancer (NSCLC). In the present study, danshensu which is a selected component of traditional oriental medicine (TOM) compound was found to reduce the radioresistance of NSCLC by inhibiting the nuclear factor-κB (NF-κB) pathway. Of the various TOM compounds reported to inhibit the IR activation of NF-κB, danshensu was chosen as a final candidate based on the results of structural comparisons with human metabolites and monoamine oxidase B (MAOB) was identified as the putative target enzyme. Danshensu decreased the activation of NF-κB by inhibiting MAOB activity in A549 and NCI-H1299 NSCLC cells. Moreover, it suppressed IR-induced epithelial-to-mesenchymal transition, expressions of NF-κB-regulated prosurvival and proinflammatory genes, and in vivo radioresistance of mouse xenograft models. Taken together, this study shows that danshensu significantly reduces MAOB activity and attenuates NF-κB signaling to elicit the radiosensitization of NSCLC.

Topics: Animals; Antineoplastic Agents, Phytogenic; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Drugs, Chinese Herbal; Epithelial-Mesenchymal Transition; Gamma Rays; Gene Expression Regulation, Neoplastic; Humans; Lactates; Lung Neoplasms; Medicine, East Asian Traditional; Mice; Mice, Nude; Monoamine Oxidase; Monoamine Oxidase Inhibitors; NF-kappa B; Radiation Tolerance; Xenograft Model Antitumor Assays

Danshensu, the major water-soluble component of Radix Salviae Miltiorrhizae (Danshen), is the basic chemical structure of various salvianolic acids. This study was to evaluate the anti-tumor activity of danshensu in a series of in vitro and in vivo models. The effect of danshensu on B16F10 melanoma cell and HUVEC proliferation were assessed by MTS assay, and cell invasion and migration were investigated by transwell chamber assay. The effect of danshensu on angiogenesis was evaluated by HUVEC migration assay, tube formation assay and chick chorioallantoic membrane assay. The expression of MMP-2, -9 and VEGF in B16F10 melanoma cell were detected by western blotting after danshensu treatment. The role of danshensu in tumor metastasis in vivo was evaluated by spontaneous and experimental B16F10 melanoma metastasis model. Although danshensu had no inhibitory effect on B16F10 melanoma cell and HUVEC proliferation, it significantly inhibited B16F10 melanoma cell invasion (at 0.05, 0.5, 5 microM) and migration (at 0.5, 5 microM). It also dramatically suppressed VEGF-induced endothelial migration (at 0.5, 5 microM), tube formation in vitro (at 4, 20 microM) and new vessel formation in CAM in vivo (100 microg/egg). Danshensu (at 5, 50 microM) significantly down-regulates protein expression of MMP-2, -9 and VEGF in B16F10 melanoma cell. In animal model, danshensu (20, 40 mg/kg) also possessed inhibitory effect on lung metastasis in spontaneous (46-day treatment) and experimental (23-day treatment) B16F10 melanoma metastasis model. All these results suggest that danshensu has anti-tumor activity by affecting on tumor angiogenesis and tumor invasion.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents, Phytogenic; Cell Movement; Cells, Cultured; Chick Embryo; Chorioallantoic Membrane; Dose-Response Relationship, Drug; Down-Regulation; Endothelial Cells; Female; Humans; Lactates; Lung Neoplasms; Matrix Metalloproteinases, Secreted; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Neoplasm Invasiveness; Neovascularization, Pathologic; Osmolar Concentration; Tumor Burden; Vascular Endothelial Growth Factors