sincalide and Prostatic-Neoplasms

Prostate cancer (PC) is the most common malignancy in male reproductive system. Sennoside A (SA) is an anthraquinone active ingredient extracted from Rheum officinale Baill., which exerts anti-tumor activity on different tumors. In the present study, the toxicity of SA on PC3 and DU 145 cells was detected via CCK-8. The effects of SA on growth, apoptosis, and autophagy were determined through CCK-8, Hoechst stain, flow cytometry, western blot, and immunofluorescence examinations. An in vivo experiment was performed in xenografted mice with intraperitoneal introduction of 10 mg/kg SA and validated via TUNEL, immunohistochemistry and western blot. The results showed that SA inhibited the cell viability with a IC50 value of 52.36 and 67.48 µM in DU 145 and PC3 cells respectively, and enhanced the apoptosis of PC3 and DU 145 cells. Additionally, SA elevated the relative LC3B expression, and the relative protein expression of LC3II/LC3I and Beclin-1, but diminished the P62 protein expression. The relative protein level of p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR was reduced with SA treatment, which was verified by the 740 Y-P application. The 740 Y-P treatments also restored the SA-induced the cell viability, apoptosis rate and relative LC3B expression. Meanwhile, SA inhibited the growth of PC cell and the relative protein level of PI3K/AKT/mTOR axis in vivo. Taken together, SA regulated the proliferation, apoptosis and autophagy via inactivating the PI3K/AKT/mTOR axis in PC.

Topics: Animals; Apoptosis; Autophagy; Cell Line, Tumor; Cell Proliferation; Humans; Male; Mice; Phosphatidylinositol 3-Kinases; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Sennosides; Signal Transduction; Sincalide; TOR Serine-Threonine Kinases

Near‑infrared fluorescence (NIRF) imaging is an attractive novel modality for the detection of cancer. A previous study defined two organic polymethine cyanine dyes as ideal NIRF probes, IR‑783 and its derivative MHI‑148, which have excellent optical characteristics, superior biocompatibility and cancer targeting abilities. To investigate the feasibility of NIRF dye‑mediated prostate cancer imaging, dye uptake and subcellular co‑localization were investigated in PC‑3, DU‑145 and LNCaP human prostate cancer cells and RWPE‑1 normal prostate epithelial cells. Different organic anion transporting peptide (OATP) inhibitors were utilized to explore the potential role of the OATP subtype, including the nonspecific OATP inhibitor bromosulfophthalein, the OATP1 inhibitor 17β‑estradiol, the selective OATP1B1 inhibitor rifampicin and the selective OATP1B3 inhibitor cholecystokinin octapeptide. NIRF dyes were also used for the simulated detection of circulating tumor cells and the rapid detection of prostate cancer in human prostate cancer tissues and prostate cancer xenografts in mouse models. The results revealed that the cancer‑specific uptake of these organic dyes in prostate cancer cells occurred primarily via OATP1B3. A strong NIRF signal was detected in prostate cancer tissues, but not in normal tissues that were stained with IR‑783. Prostate cancer cells were recognized with particular NIR fluorescence in isolated mononuclear cell mixtures. The results of the present study demonstrated that NIRF dye‑mediated imaging is a feasible and practicable method for prostate cancer detection, although further investigative studies are required before clinical translation.

Topics: Animals; Carbocyanines; Cell Line; Estradiol; Flow Cytometry; Fluorescent Dyes; Humans; Liver-Specific Organic Anion Transporter 1; Male; Mice; Mice, Nude; Microscopy, Confocal; Neoplastic Cells, Circulating; Organic Anion Transporters; Organic Anion Transporters, Sodium-Independent; Organic Cation Transport Proteins; Prostate; Prostatic Neoplasms; Rifampin; Sincalide; Solute Carrier Organic Anion Transporter Family Member 1B3; Spectroscopy, Near-Infrared; Sulfobromophthalein; Transplantation, Heterologous

C-C chemokine ligand 2 (CCL2) is a chemokine that has been demonstrated to play a pivotal role in prostate cancer tumorigenesis and metastasis. These effects are mediated by the ligand binding to the G protein-coupled receptor (GPCR) C-C chemokine receptor 2 (CCR2). It has recently been demonstrated that CCL2 increases Akt phosphorylation in prostate cancer cells, and prevents prostate cancer cells from autophagic death through activation of Akt pathway. The purpose of this study was to determine the mechanism by which CCL2 activates Akt in prostate cancer PC-3 cell line. CCL2-induced phosphorylation of Akt was inhibited by pertussis toxin and the adenylyl cyclase inhibitor SQ22536. Akt phosphorylation was promoted by prior treatment with cholera toxin. The results suggest that CCL2-induced Akt phosphorylation is mediated by the Galphai complex and adenylyl cyclase. This is the first study that demonstrates a direct involvement of adenylyl cyclase in CCL2-induced Akt phosphorylation.

Topics: Adenylyl Cyclase Inhibitors; Adenylyl Cyclases; Adjuvants, Immunologic; Blotting, Western; Chemokine CCL2; Cholera Toxin; Humans; Male; Pertussis Toxin; Phosphatidylinositol 3-Kinases; Phosphorylation; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; rho GTP-Binding Proteins; rho-Associated Kinases; Signal Transduction; Sincalide; Tumor Cells, Cultured