TMPYP4 exerted antitumor effects in human cervical cancer cells through activation of p38 mitogen-activated protein kinase

Abstract

BackgroundThe aim of the present study was to investigate the potential effects of the 5,10,15,20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4) on the proliferation and apoptosis of human cervical cancer cells and the underlying mechanisms by which TMPyP4 exerted its actions.ResultsAfter human cervical cancer cells were treated with different doses of TMPyP4, cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) method, the apoptosis was observed by flow cytometry (FCM), and the expression of p38 mitogen-activated protein kinase (MAPK), phosphated p38 MAPK (p-p38 MAPK), capase-3, MAPKAPK2 (MK-2) and poly ADP-ribose polymerase (PARP) was measured by Western blot analysis. The analysis revealed that TMPyP4 potently suppressed cell viability and induced the apoptosis of human cervical cancer cells in a dose-dependent manner. In addition, the up-regulation of p-p38 MAPK expression levels was detected in TMPyP4-treated human cervical cancer cells. However, followed by the block of p38 MAPK signaling pathway using the inhibitor SB203580, the effects of TMPyP4 on proliferation and apoptosis of human cervical cancer cells were significantly changed.ConclusionsIt was indicated that TMPyP4-inhibited proliferation and -induced apoptosis in human cervical cancer cells was accompanied by activating the p38 MAPK signaling pathway. Taken together, our study demonstrates that TMPyP4 may represent a potential therapeutic method for the treatment of cervical carcinoma.

miR-22-Notch Signaling Pathway Is Involved in the Regulation of the Apoptosis and Autophagy in Human Ovarian Cancer Cells

“…25) In epithelial ovarian cancer, the expression of miR-22 is downregulated. 18) Our study also suggests that miR-22 expression is significantly suppressed in both OVCAR-3 and SKOV3 cells compared to normal human ovarian cells. Conversely, in some cases, miR-22 becomes an important activator and its significant upregulation is observed in pancreatic cancer patients, 7) and breast tumor samples.…”

“…17) There was ever a report providing the evidence that miR-22 expression is heavily decreased in epithelial ovarian cancer. 18) To further demonstrate the functions of miR-22 in ovarian cancer, using cultured ovarian cancer cell lines OVCAR-3 and SKOV3, we discover that miR-22 upregulation is responsible for the reduction of autophagy and the promotion of apoptosis in ovarian cancer cells by targeting the Notch signal pathway. Therefore, miR-22 may be considered as a potential therapeutic target for the treatment of ovarian cancer.…”

Pyrimethamine Elicits Antitumor Effects on Prostate Cancer by Inhibiting the p38-NF-κB Pathway

“…The p38 MAPK family consists of four isoforms (p38-MAPKa, p38-MAPKb, p38-MAPKg, and p38-MAPKd), which share varied degrees of sequence homology and activity (Zou and Blank, 2017). Several studies have suggested that p38 MAPK is activated in human cancers and is commonly correlated with poor prognosis (Hong et al, 2015;Cao et al, 2016;Mo et al, 2016;Yuan et al, 2016;Cheng and Cao, 2017). Furthermore, small molecular inhibitors of p38 MAPK have been gradually utilized to overpower cancer cells (Campbell et al, 2014;Gilani et al, 2016;Chowchaikong et al, 2018).…”

Nucleophosmin in Its Interaction with Ligands

“…NPM1 binds nucleic acids, including rDNA G-quadruplex sequences both in vitro and in vivo, through its C-terminal domain and depending critically on its folded state [36,42]. TmPyP4 (tetra-N-methyl-pyridyl porphyrin), a cationic porphyrin able to bind G-quadruplex DNA structures with high affinity, has been investigated by several groups for its anticancer and antiproliferative activities [156][157][158][159]. As to NPM1, TmPyP4 was shown to effectively displace NPM1 from nucleoli in both wild-type and mutant NPM1-expressing AML cells, without affecting NPM1 total content [42,160].…”