Novel functions for 2-phenylbenzimidazole-5-sulphonic acid: Inhibition of ovarian cancer cell responses and tumour angiogenesis.

Abstract

In this study, we investigated the effects and molecular mechanisms of 2-phenylbenzimidazole-5-sulphonic acid (PBSA), an ultraviolet B protecting agent used in sunscreen lotions and moisturizers, on ovarian cancer cell responses and tumour angiogenesis. PBSA treatment markedly blocked mitogen-induced invasion through down-regulation of matrix metalloproteinase (MMP) expression and activity in ovarian cancer SKOV-3 cells. In addition, PBSA inhibited mitogen-induced cell proliferation by suppression of cyclin-dependent kinases (Cdks), but not cyclins, leading to pRb hypophosphorylation and G1 phase cell cycle arrest. These anti-cancer activities of PBSA in ovarian cancer cell invasion and proliferation were mediated by the inhibition of mitogen-activated protein kinase kinase 3/6-p38 mitogen-activated protein kinase (MKK3/6-p38MAPK ) activity and subsequent down-regulation of MMP-2, MMP-9, Cdk4, Cdk2 and integrin β1, as evidenced by treatment with p38MAPK inhibitor SB203580. Furthermore, PBSA suppressed the expression and secretion of vascular endothelial growth factor in SKOV-3 cells, leading to inhibition of capillary-like tubular structures in vitro and angiogenic sprouting ex vivo. Taken together, our results demonstrate the pharmacological effects and molecular targets of PBSA on modulating ovarian cancer cell responses and tumour angiogenesis, and suggest further evaluation and development of PBSA as a promising chemotherapeutic agent for the treatment of ovarian cancer.

• Authors: Min Su Kim, Jae Hyeon Kim, Eun-Kyung Ahn, Young-Rak Cho, Surim Han, Choong-Hyun Lee, Gyu-Un Bae, Joa Sub Oh, Kyu-Bong Kim, Dong-Wan Seo
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 4 Pg. 2688-2700 (02 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 31958895 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Adipates
• Imidazoles
• Intracellular Signaling Peptides and Proteins
• Pyridines
• Succinates
• Vascular Endothelial Growth Factor A
• poly(tetramethylene succinate-co-tetramethylene adipate)
• MAP-kinase-activated kinase 3
• Protein Serine-Threonine Kinases
• Cyclin-Dependent Kinases
• p38 Mitogen-Activated Protein Kinases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• SB 203580

Topics

• Adipates (pharmacology)
• Animals
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cyclin-Dependent Kinases (metabolism)
• Down-Regulation (drug effects)
• Female
• G1 Phase (drug effects)
• Human Umbilical Vein Endothelial Cells
• Humans
• Imidazoles (pharmacology)
• Intracellular Signaling Peptides and Proteins (metabolism)
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Neovascularization, Pathologic (drug therapy, metabolism)
• Ovarian Neoplasms (drug therapy, metabolism)
• Protein Serine-Threonine Kinases (metabolism)
• Pyridines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Succinates (pharmacology)
• Vascular Endothelial Growth Factor A (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)