peoniflorin and Stomach-Neoplasms

Paeoniflorin, a representative pinane monoterpene glycoside in plants of Paeoniaceae family, possesses promising anticancer activities on diverse tumours. This paper summarized the advance of Paeoniflorin on cancers in vivo and in vitro, discussed the related molecular mechanisms, as well as suggested some perspectives of the future investigations.. Anticancer activities of paeoniflorin have been comprehensively investigated, including liver cancer, gastric cancer, breast cancer, lung cancer, pancreatic cancer, colorectal cancer, glioma, bladder cancer and leukaemia. Furthermore, the potential molecular mechanisms corresponding to the antitumour effects of Paeoniflorin might be related to the following aspects: inhibition of tumour cell proliferation and neovascularization, induction apoptosis, and inhibition of tumour invasion and metastasis.. Paeoniflorin has wide spectrum antitumour activities; however, in vivo and clinical investigations on antitumour effect of Paeoniflorin are lacking which should be focused on further studies. Our present review on antitumour effects of Paeoniflorin would be beneficial for the further molecular mechanisms study, candidate antitumour drug development and clinical research of Paeoniflorin in the future.

Topics: Animals; Apoptosis; Breast Neoplasms; Cell Proliferation; Colorectal Neoplasms; Glioma; Glucosides; Humans; Leukemia; Liver Neoplasms; Lung Neoplasms; Monoterpenes; Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Urinary Bladder Neoplasms

To investigate the inhibitory effects of paeoniflorin on migration- and invasion-promoting capacities of gastric cancer associated fibroblasts (GCAFs) and to explore the molecular mechanism underlying the effects.. Paired gastric normal fifbroblast (GNF) and GCAF cultures were established from resected tissues. GCAFs were treated with control medium, or 2.5, 5 or 10 μg/mL paeoniflorin. Conditioned media were prepared from GNFs, GCAFs, control-treated GCAFs and paeoniflorin-treated GCAFs, and used to culture AGS human gastric cancer cells. The migration and invasion capacities of AGS cells were determined with wound healing test and transwell invasion assay, respectively. The interleukin 6 (IL-6) mRNA and microRNA-149 expression in GCAFs were detected by reverse transcription-quantitative polymerase chain reaction. The IL-6 protein expression and secretion by GCAFs were measured with Western blot and enzyme-linked immunosorbent assay analysis, respectively. The protein levels of phosphorylated signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase (MMP) and MMP9 in AGS cells were examined by Western blot.. GCAFs displayed enhanced capacities to induce AGS cell migration and invasion as compared with GNFs. Paeoniflorin treatment significantly inhibited the migration- and invasion-promoting capacities of GCAFs (P<0.05). GCAFs produced and secreted more IL-6 into the conditioned medium than GNFs, leading to over-activation of STAT3-MMP signaling in AGS cells. Paeoniflorin suppressed IL-6 production and secretion by up-regulating microRNA149 expression in GCAFs, and subsequently prevented GCAFs from activating IL-6-STAT3-MMP signaling of AGS cells.. Paeoniflorin inhibits the migration- and invasion-promoting capacities of GCAFs by targeting microRNA-149 and IL-6. Paeoniflorin is potentially a novel therapeutic agent against cancer microenvironment.

Topics: Adenocarcinoma; Adult; Cancer-Associated Fibroblasts; Cell Movement; Cells, Cultured; Culture Media, Conditioned; Down-Regulation; Fibroblasts; Gene Expression Regulation, Neoplastic; Glucosides; Humans; Interleukin-6; Male; Margins of Excision; MicroRNAs; Monoterpenes; Neoplasm Invasiveness; Primary Cell Culture; Stomach Neoplasms; Tumor Microenvironment

To examine the potential anti-tumor activity of paeoniflorin in the human gastric carcinoma cell line MGC-803.. Cell viability and cytotoxic effects in MGC-803 cells were analyzed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay, respectively. Cell apoptosis of MGC-803 cells was measured using flow cytometry, DAPI staining assay and caspase-3 activity assay. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression of microRNA-124 (miR-124) in response to paeoniflorin. The expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), phospho-Akt (p-Akt) and phospho-signal transducer and activator of transcription 3 (p-STAT3) were also measured by quantitative RT-PCR and Western blot analysis in normal, miR-124 and anti-miR-124 over-expressing MGC-803 cells, treated with paeoniflorin.. Paeoniflorin was found to inhibit MGC-803 cell viability in a dose-dependent manner. Paeoniflorin treatment was associated with the induction of apoptosis and caspase-3 activity in MGC-803 cells. Paeoniflorin treatment significantly increased miR-124 levels and inhibited the expression of PI3K, Akt, p-Akt and p-STAT3 in MGC-803 cells. Interestingly, the over-expression of miR-124 inhibits PI3K/Akt and phospho-STAT3 expressions in MGC-803 cells. PI3K agonist (IGF-1, 1 μg/10 μL) or over-expression of STAT3 reversed the effect of paeoniflorin on the proliferation of MGC-803 cells. Over-expression of anti-miR-124 in MGC-803 cells reversed paeoniflorin-induced up-regulation.. In summary, the in vitro data suggest that paeoniflorin is a potential novel therapeutic agent against gastric carcinoma, which inhibits cell viability and induces apoptosis through the up-regulation of miR-124 and suppression of PI3K/Akt and STAT3 signaling.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Blotting, Western; Carcinoma; Caspase 3; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Glucosides; Humans; MicroRNAs; Monoterpenes; Phosphatidylinositol 3-Kinase; Phosphorylation; Proto-Oncogene Proteins c-akt; Real-Time Polymerase Chain Reaction; Signal Transduction; STAT3 Transcription Factor; Stomach Neoplasms; Time Factors; Transfection; Up-Regulation

Research into the evasion of drug resistance and adverse effects is highly significant and urgent in the clinic. Therefore, accumulating studies have focused on the development of novel target-specific molecules related to drug resistance, and the establishment of rational therapeutic approaches. Currently, studies have shown that NF-κB activation may play an essential role in the development of chemotherapy resistance in carcinoma cells. Paeoniflorin, a principal bioactive component of the root of Paeonia lactiflora Pall., has been reported to exhibit various pharmacological effects. In the present study, we reported for the first time that paeoniflorin at non-toxic concentrations may effectively modulate multidrug resistance (MDR) of the human gastric cancer cell line SGC7901/vincristine (VCR) via the inhibition of NF-κB activation and, at least partly, by subsequently downregulating its target genes MDR1, BCL-XL and BCL-2.

Topics: Antineoplastic Agents, Phytogenic; ATP Binding Cassette Transporter, Subfamily B, Member 1; bcl-X Protein; Benzoates; Bridged-Ring Compounds; Cell Line, Tumor; Down-Regulation; Drug Resistance, Neoplasm; Enzyme Activation; Glucosides; Humans; Monoterpenes; NF-kappa B; Paeonia; Plant Roots; Proto-Oncogene Proteins c-bcl-2; Stomach Neoplasms

We sought to determine whether paeoniflorin enhances 5-fluorouracil-induced apoptosis in human gastric carcinoma cells, and, if so, to determine the relationship between this apoptosis and NF-kappaB activation.. Paeoniflorin was diluted to different concentrations and added to gastric carcinoma cells (SGC-7901) at different times. Western blot was used to test the expression of NF-kappaB in nuclear and I kappaB alpha, p-I kappaB alpha, IKK alpha in cytoplasm. Further, the intranuclear expression of NF-kappaB was confirmed by ELISA assay. The impact of paeoniflorin and 5-fluorouracil on cell apoptosis of gastric carcinoma cells was estimated by flow cytometry.. Paeoniflorin revealed dramatic inhibition of NF-kappaB activity in the nuclei of the cells. The inhibition pattern of NF-kappaB was exhibited in a time- and dose-dependent manner, which was confirmed by Western blot and ELISA. Decreased nuclear translocation of NF-kappaB induced by paeoniflorin was found by preventing I kappaB alpha phosphorylation. Moreover, 5-fluorouracil-induced cell apoptosis was promoted by paeoniflorin in gastric carcinoma cells.. Paeoniflorin can inhibit NF-kappaB activity of SGC-7901 cells, and enhance 5-fluorouracil-induced apoptosis of gastric carcinoma cells.

Topics: Active Transport, Cell Nucleus; Antineoplastic Agents; Apoptosis; Benzoates; Bridged-Ring Compounds; Cell Line, Tumor; Cell Nucleus; Fluorouracil; Glucosides; Humans; I-kappa B Proteins; Monoterpenes; NF-kappa B; NF-KappaB Inhibitor alpha; Phosphorylation; Stomach Neoplasms