Dihydroisotanshinone I combined with radiation inhibits the migration ability of prostate cancer cells through DNA damage and CCL2 pathway.

BACKGROUND: Radiotherapy plays an important role in the treatment of prostate cancer. Despite that sophisticated techniques of radiotherapy and radiation combined with chemotherapy were applied to the patients, some tumors may recur. Therefore, the study investigated the effect of dihydroisotanshinone I (DT) and the combination treatment of 5 µM DT and 5Gy irradiation (IR) against the migration ability of prostate cancer cells. METHODS: DT and the combination treatment were studied for its biological activity against migration ability of prostate cancer cells with transwell migration assay. Subsequently, we tried to explore the underlying mechanism with ELISA, flow cytometry and Western's blotting assay. RESULTS: The results showed that DT and the combination treatment substantially inhibited the migration ability of prostate cancer cells. DT and the combined treatment can decrease the ability of macrophages to recruit prostate cancer cells. Mechanistically, DT and the combination treatment reduced the secretion of chemokine (C-C Motif) Ligand 2 (CCL2) from prostate cancer cells. We also found that DT treatment induced the cell cycle of prostate cancer cells entering S phase and increased the protein expression of DNA damage response proteins (rH2AX and phosphorylated ataxia telangiectasia-mutated [ATM]) in DU145 cells and PC-3 cells. CONCLUSIONS: DT displays radiosensitization and antimigration effects in prostate cancer cells by inducing DNA damage and inhibiting CCL2 secretion. We suggest that DT can be used as a novel antimetastatic cancer drug or radiosensitizer in the armamentarium of prostate cancer management.

Danshen improves survival of patients with colon cancer and dihydroisotanshinone I inhibit the proliferation of colon cancer cells via apoptosis and skp2 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Danshen (Salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. However, it's definite clinical effect and mechanism on colon carcinoma is unclear. AIM OF THE STUDY: To test the hypothesis that the protective effect of danshen on colon cancer and discover the bioactive compounds through in vitro study. MATERIALS AND METHODS: We conducted a nationwide cohort study by using population-based data from the Taiwan National Health Insurance Research Database (NHIRD). The study cohort comprised patients diagnosed with malignant neoplasm of colon (ICD-9-CM codes:153) in catastrophic illness database between January 1, 2000, and December 31, 2010. We used the Kaplan-Meier method to estimate colon [corrected] cancer cumulative incidences. Next, human colon cancer cells (HCT 116 cells and HT29 cells) were used to investigate the effect of dihydroisotanshinone I (DT) on the proliferation and apoptosis of human colon cancer cells and the underlying mechanism through XTT assay and flow cytometry. The in vivo effect of DT treatment was investigated through a xenograft nude mouse model. RESULTS: In our study, the in vivo protective effect of danshen in the different stage of colon cancer patients was validated through data from the National Health Insurance Research Database in Taiwan. In vitro, we found that dihydroisotanshinone I (DT), a bioactive compound present in danshen, can inhibit the proliferation of colon carcinoma cells, HCT 116 cells and HT-29 cells. Moreover, DT induced apoptosis of colorectal cancer cells. DT also repressed the protein expression of Skp2 (S-Phase Kinase Associated Protein 2) and the mRNA levels of its related gene, Snail1 (Zinc finger protein SNAI1) and RhoA (Ras homolog gene family, member A). In addition, DT also blocked the colon cancer cells recruitment ability of macrophage by decreasing CCL2 secretion in macrophages. DT treatment also significantly inhibited the final tumor volume in a xenograft nude mouse model. CONCLUSION: Danshen has protective effects in colon cancer patients, which could be attributed to DT through blocking the proliferation of colon cancer cells through apoptosis.

Anti-cancer effect of danshen and dihydroisotanshinone I on prostate cancer: targeting the crosstalk between macrophages and cancer cells via inhibition of the STAT3/CCL2 signaling pathway.

Danshen (Salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. In our study, the in vivo protective effect of danshen in prostate cancer patients was validated through data from the National Health Insurance Research Database in Taiwan. In vitro, we discovered that dihydroisotanshinone I (DT), a bioactive compound present in danshen, can inhibit the migration of both androgen-dependent and androgen-independent prostate cancer cells. In addition, we noted that DT substantially inhibited the migratory ability of prostate cancer cells in both a macrophage-conditioned medium and macrophage/prostate cancer coculture medium. Mechanistically, DT both diminished the ability of prostate cancer cells to recruit macrophages and reduced the secretion of chemokine (C-C motif) ligand 2 (CCL2) from both macrophages and prostate cancer cells in a dose-dependent manner. Moreover, DT inhibited the protein expression of p-STAT3 and decreased the translocation of STAT3 into nuclear chromatin. DT also suppressed the expression of tumor epithelial-mesenchymal transition genes, including RhoA and SNAI1. In conclusion, danshen can prolong the survival rate of prostate cancer patients in Taiwan. Furthermore, DT can inhibit the migration of prostate cancer cells by interrupting the crosstalk between prostate cancer cells and macrophages via the inhibition of the CCL2/STAT3 axis. These results may provide the basis for a new therapeutic approach toward the treatment of prostate cancer progression.

Interplay of mutual electric and magnetic couplings between three-dimensional split-ring resonators.

We experimentally and theoretically study the interplay between capacitive electric and inductive magnetic couplings in infrared metamaterials consisting of densely-packed three-dimensional (3D) meta-atoms. The meta-atom is made of metal-stress-driven assembled 3D split-ring resonators to exhibit strong bi-anisotropy, where electric and magnetic resonances occur simultaneously. By varying the spatial arrangement of the arrayed meta-atoms, the mutual coupling between meta-atoms dramatically modifies their mode profiles and resultant spectral responses. The corresponding numerical simulations evidently retrieved current densities and magnetic field strengths, as well as the transmittance, to reveal the important resonant behavior in the coupled meta-atom systems. We conclude that the mutual electric coupling between the neighboring meta-atoms plays a crucial role to the scattering behaviors of the bi-anisotropic metamaterials.

pH-sensitive behavior of two-component hydrogels composed of N,O-carboxymethyl chitosan and alginate.

A two-component pH-sensitive hydrogel system composed of a water-soluble chitosan derivative (N,O-carboxymethyl chitosan, NOCC) and alginate cross-linked by genipin, glutaraldehyde or Ca2+ was investigated. Preparation and structures of these hydrogels and their swelling characteristics and release profiles of a model protein drug (bovine serum albumin, BSA) in simulated gastrointestinal media are reported. At pH 1.2, the swelling ratios of the hydrogels cross-linked by distinct methods were limited. Of note is that the lowest swelling ratios of test hydrogels were found at pH 4.0. At pH 7.4, the carboxylic acid groups on test hydrogels became progressively ionized and led to a significant swelling. There was barely any BSA released from the glutaraldehyde-cross-linked hydrogel throughout the entire course of the study. The amounts of BSA released at pH 1.2 from the genipin- and Ca(2+)-cross-linked hydrogels were relatively low (approx. 20%). At pH 4.0, there was still significant BSA release from the Ca(2+)-cross-linked hydrogel, while the cumulative BSA released from the genipin-cross-linked hydrogel was limited due to its shrinking behavior. At pH 7.4, the amount of BSA released from the genipin- and Ca(2+)-cross-linked hydrogels increased significantly (approx. 80%) because the swelling of both test hydrogels increased considerably. The aforementioned results indicated that the swelling behaviors and drug-release profiles of these test hydrogels are significantly different due to their distinct cross-linking structures.