peoniflorin and Colorectal-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

Paeoniflorin (PF) is a natural plant ingredient with remarkable antitumor effects. Herein, we investigated the biological effects and mechanism of PF in colorectal cancer (CRC) cell stemness. The messenger RNA (mRNA) and protein expressions were assessed using quantitative real-time polymerase chain reaction and western blot. The viability, proliferation, and migration and invasion of CRC cells were evaluated using cell counting kit-8, clone-formation, and transwell migration and invasion assays, respectively. The sphere-formation capacity was determined using the sphere-formation assay. A dual-luciferase reporter gene assay was employed to analyze the interaction between miR-3194-5p and catenin beta-interacting protein 1 (CTNNBIP1). The viability, migration, invasion, epithelial-mesenchymal transition, and stemness of CRC cells were repressed by PF. MiR-3194-5p was upregulated in CRC tissues and cells. MiR-3194-5p knockdown suppressed CRC cell stemness, while miR-3194-5p overexpression had the opposite effect. In addition, the inhibition of CRC cell stemness caused by PF was eliminated by miR-3194-5p overexpression. CTNNBIP1 functioned as the target of miR-3194-5p, whose knockdown abrogated the repression of CRC cell stemness and Wnt/β-catenin signaling activation by PF.PF regulated the miR-3194-5p/CTNNBIP1/Wnt/β-catenin axis to repress CRC cell stemness.

Topics: beta Catenin; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs

Chronic inflammation plays a positive role in the development and progression of colitis-associated colorectal cancer (CAC). Medicinal plants and their extracts with anti-inflammatory and immunoregulatory properties may be an effective treatment and prevention strategy for CAC. This research aimed to explore the potential chemoprevention of paeoniflorin (PF) for CAC by network pharmacology, molecular docking technology, and in vivo experiments. The results showed that interleukin-6 (IL-6) is a key target of PF against CAC. In the CAC mouse model, PF increased the survival rate of mice and decreased the number and size of colon tumors. Moreover, reduced histological score of colitis and expression of Ki-67 and PCNA were observed in PF-treated mice. In addition, the chemoprevention mechanisms of PF in CAC may be associated with suppression of the IL-6/STAT3 signaling pathway and the IL-17 level. This research provides experimental evidence of potential chemoprevention strategies for CAC treatment.

Topics: Animals; Cell Transformation, Neoplastic; Chemoprevention; Colitis-Associated Neoplasms; Colorectal Neoplasms; Disease Models, Animal; Glucosides; Interleukin-6; Mice; Molecular Docking Simulation; Monoterpenes; Network Pharmacology; STAT3 Transcription Factor

Paeoniflorin (PF) exhibits tumor suppressive functions in a variety of human cancers. However, the function of PF and molecular mechanism in colorectal cancer are elusive. In the present study, we investigated whether PF could exert its antiproliferative activity, anti-migration, and anti-invasive function in colorectal cancer cells. We found that PF inhibited cell growth and induced apoptosis and blocked cell cycle progression in the G0/G1 phase in colorectal cancer cells. Moreover, we found that PF suppressed cell migration and invasion in colorectal cancer cells. FoxM1 has been reported to play an important oncogenic role in human cancers. We also determine whether PF inhibited the expression of FoxM1, leading to its anti-cancer activity. We found that PF treatment in colorectal cancer cells resulted in down-regulation of FoxM1. The rescue experiments showed that overexpression of FoxM1 abrogated the tumor suppressive function induced by PF treatment. Notably, depletion of FoxM1 promoted the anti-tumor activity of PF in colorectal cancer cells. Therefore, inhibition of FoxM1 could participate in the anti-tumor activity of PF in colorectal cancer cells.

Topics: Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Forkhead Box Protein M1; Glucosides; Humans; Monoterpenes; Neoplasm Invasiveness

BACKGROUND Colorectal cancer is one of the leading causes of death in China, and the development of effective drugs is urgently needed. Here, we report on Paeoniflorin (PF), a product isolated from the roots of the peony plant, as a possible candidate because of its anti-tumor effects on epithelial-to-mesenchymal transition (EMT) of PF in human colorectal cancer (CRC). MATERIAL AND METHODS Cell proliferation, wound healing, and Transwell assays were used to analyze the effects of PF on in vitro cell migration and invasion of HCT116 and SW480, 2 colorectal cancer cell lines. The tumor xenograft model was used to verify the anti-metastasis effects of PF in vivo. The RNA and protein levels of epithelia-cadherin (E-cadherin), Vimentin, and histone deacetylase2 (HDAC2) were measured by qPCR and Western blot analysis to explore the mechanism involved. RESULTS Our results showed that PF inhibited colorectal cancer cell migration and invasion and suppressed the metastatic potential of the cancer cells in vivo. Moreover, PF significantly decreased the expression of HDAC2 and Vimentin, while increasing the expression of E-cadherin. CONCLUSIONS These results suggest that PF inhibits colorectal cancer cell migration and invasion ability and reverses the EMT process, through inhibiting the expression of HDAC2, and then affects the expression level of E-cadherin and Vimentin at the cell level. Our results were also verified in the tumor xenograft model. This indicates that PF may be a candidate for colorectal cancer treatment.

Topics: Animals; Cadherins; Cell Line, Tumor; Cell Movement; Cell Proliferation; China; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Glucosides; Histone Deacetylase 2; Humans; Medicine, Chinese Traditional; Mice; Mice, Nude; Monoterpenes; Signal Transduction; Vimentin; Wound Healing; Xenograft Model Antitumor Assays

The aim of the therapy of human malignancies is the inhibition of cell proliferation and/or induction of apoptosis. In present experiment, we investigated the in vitro and in vivo anticancer effects and associated mechanisms of paeoniflorin (PF), isolated from the paeony root, against colorectal cancer. In vitro, cell growth assay obviously showed the inhibition of tumor cell growth in a dose-dependent manner. Flow cytometry analysis showed that PF could mainly have the cell cycle arrest at G1, which is associated with DNA damage and activation of p53/14-3-3 zeta (ζ). The pro-apoptotic effect of PF was demonstrated by Annexin V-PI staining, and activation of caspase-3 and caspase-9 by Western immunoblotting. In vivo, the results showed that positive cells of PCNA in PF and docetaxel-treated group was decreased to 30% and 15% compared with control group of tumors, respectively. But apoptosis cells in PF- and docetaxel treated groups studied by TUNEL is increased to 40 ± 1.2% and 30 ± 1.5% compared with 24 ± 2.3% in negative control, respectively. Furthermore, the efficiency of tumor-bearing mice treated by PF was superior to docetaxel in vivo. Overall, PF may be an effective chemopreventive agent against colorectal cancer HT29, and the mechanism could be mediated via an regulation of p53/14-3-3ζ.

Topics: Animals; Apoptosis; Benzoates; Bridged-Ring Compounds; Caspase 3; Caspase 9; Cell Cycle; Cell Division; Colorectal Neoplasms; Electrophoresis, Agar Gel; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Glucosides; HT29 Cells; Humans; Immunohistochemistry; Mice; Mice, Nude; Monoterpenes; Xenograft Model Antitumor Assays