Dataset Information

Pien Tze Huang induces apoptosis and inhibits proliferation of 5-fluorouracil-resistant colorectal carcinoma cells via increasing miR-22 expression.

ABSTRACT: The well-known traditional Chinese medicine formula Pien Tze Huang (PZH) has long been used to treat various malignancies, including colorectal cancer (CRC). It was recently reported that PZH possesses the ability to overcome multidrug resistance in CRC cells. In the present study, a 5-fluorouracil (5-FU) resistant human CRC cell line (HCT-8/5-FU) was used to further evaluate the effect of PZH on chemotherapy (chemo)-resistance and investigate the mechanisms through which this occurs. The results identified that PZH significantly reduced the viability and cell density of HCT-8/5-FU cells in a dose- and time-dependent manner (P<0.05). PZH inhibited cell survival, reduced the proportion of cells in S-phase, and suppressed the expression of pro-proliferative proteins cyclin D1 and cyclin-dependent kinase 4. In addition, PZH treatment induced nuclear condensation and fragmentation, activated caspase-9 and -3 and increased the pro-apoptotic Bcl-2-associated X protein/B-cell lymphoma 2 protein ratio. Furthermore, PZH treatment upregulated the expression of microRNA-22 (miR-22) and downregulated the expression of c-Myc (a target gene of miR-22). In conclusion, the findings from the present study suggest that PZH can overcome chemo-resistance in cancer cells, likely through increasing miR-22 expression, and by reversing the imbalance between levels of proliferation and apoptosis.

SUBMITTER: Chen Z

PROVIDER: S-EPMC5639424 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pien Tze Huang induces apoptosis and inhibits proliferation of 5-fluorouracil-resistant colorectal carcinoma cells via increasing miR-22 expression.

Chen Zhaorong Z Shen Aling A Liu Liya L Chen Youqin Y Chu Jianfeng J Cai Qiaoyan Q Qi Fei F Sferra Thomas Joseph TJ Peng Jun J

Experimental and therapeutic medicine 20170816 4

The well-known traditional Chinese medicine formula Pien Tze Huang (PZH) has long been used to treat various malignancies, including colorectal cancer (CRC). It was recently reported that PZH possesses the ability to overcome multidrug resistance in CRC cells. In the present study, a 5-fluorouracil (5-FU) resistant human CRC cell line (HCT-8/5-FU) was used to further evaluate the effect of PZH on chemotherapy (chemo)-resistance and investigate the mechanisms through which this occurs. The result ...[more]

PMID: 29042944

Similar Datasets

Project description:The Chinese medicine formula Pien Tze Huang (PZH) has been applied to the treatment of various diseases, the reported anti-tumor mechanisms included regulation of inflammation-associated cytokine secretion and cancer growth pathways. However, the potential influence of PZH on tumor metabolism remains unclear. This study aimed to investigate the global effect of PZH on hepatocellular carcinoma (HCC) compared with the anti-tumor agent sorafenib based on tandem mass tag (TMT) label proteomic and phosphoproteomic analysis in addition to parallel reaction monitoring (PRM) verification. It was observed that PZH could inhibit tumor weight by 59-69% in different concentrations. TMT proteomic studies indicated that fructose/mannose metabolism and glucagon signaling pathway in PZH group, and arachidonic acid metabolism and PPAR signaling pathway in sorafenib group, were significantly enriched, while glycolysis/gluconeogenesis pathway was found to be enriched remarkably both in PZH and sorafenib groups in TMT phosphoproteomic study. PRM verification further indicated that both PZH and sorafenib could down-regulate phosphorylations of the glycolytic enzymes phosphofructokinases 1, fructose-bisphosphate Aldolase A, phosphoglycerate mutase 2 and lactate dehydrogenase A chain, while phosphorylations of long chain fatty acid CoA ligase in fatty acid activation and acetyl-coenzyme A synthetase in glycolysis were significantly inhibited by PZH and sorafenib, respectively. This study proposed that PZH shared a similar anti-tumor mechanism of metabolic regulation to sorafenib, but differed in the regulation of some metabolic nodes. This is the first time to uncover the relationship between the anti-tumor effect of PZH and metabolic related enzymes, which distinguished from the known mechanisms of PZH. These data provided the potential molecular basis for PZH acting as a therapeutic drug for HCC, and offered cues of manipulation on Warburg effect under the treatment of PZH.

Project description:Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by infiltrating inflammatory cells and demyelinating lesions, and T helper (Th) cells play critical roles in the pathogenesis of MS. There is still lack of effective treatments currently. Pien Tze Huang (PZH), a traditional Chinese medicine formula, has been proved to have anti-inflammatory, neuroprotective, and immunoregulatory effects. However, whether PZH can be used to treat MS is still obscure. This study aimed to investigate the possible therapeutic effect and the underlying action mechanism of PZH in relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE) mice. Female SJL/J mice were immunized with myelin proteolipid protein 139-151 (PLP139-151) and pertussis toxin to establish RR-EAE model. Mice were then randomly divided into normal group, model group, PZH group and positive control group (fingolimod, FTY-720), and drugs were orally administered for 60 days from the day 10 after immunization. Sera of mice were collected for ELISA detection. Tissues of CNS were harvested for hematoxylin-eosin (H-E) and luxol fast blue (LFB) staining. Furthermore, Th1, Th17 cells and their related cytokines in the CNS were detected by flow cytometry and quantitative real-time PCR, respectively. Proteins involved in STAT and NF-κB signaling pathways were detected by western blot. The results showed that PZH-treated mice displayed mild or moderate clinical symptoms compared with untreated EAE mice that exhibited severe clinical symptoms. PZH remarkably reduced inflammatory cell infiltration and myelin damage in the CNS of EAE mice. It markedly down-regulated the levels of IFN-γ and IL-17A in sera of EAE mice. Moreover, PZH could reduce the percentages of Th1 and Th17 cells. It also suppressed the production of transcription factors ROR-γt and T-bet as well as the mRNA levels of their downstream pro-inflammatory cytokines, such as IFN-γ and IL-17A. Furthermore, PZH could inhibit the phosphorylation of some key proteins in the STAT and NF-κB signaling pathways. In conclusion, the study demonstrated that PZH had a therapeutic effect on RR-EAE mice, which was associated with the modulation effect on Th1 and Th17 cells.

Dataset Information

Pien Tze Huang induces apoptosis and inhibits proliferation of 5-fluorouracil-resistant colorectal carcinoma cells via increasing miR-22 expression.

Publications

Pien Tze Huang induces apoptosis and inhibits proliferation of 5-fluorouracil-resistant colorectal carcinoma cells via increasing miR-22 expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets