Phosphodiesterase 5 Inhibitor Potentiates Epigallocatechin 3-O-Gallate-Induced Apoptotic Cell Death via Activation of the cGMP Signaling Pathway in Caco-2 Cells

Jaehoon Bae, Kwanwoo Lee, Ji Sun Park, Jinseok Jung, Hirofumi Tachibana, Yoshinori Fujimura, Motofumi Kumazoe, Jae Sung Lim, Young Chang Cho, Seung Jae Lee, Su Jin Park

Research output: Contribution to journalArticlepeer-review

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Abstract

Epigallocatechin 3-O-gallate (EGCG) is a predominant component in green tea with various health benefits. The 67 kDa laminin receptor (67LR) is a nonintegrin cell surface receptor that is overexpressed in various types of cancer; 67LR was identified a cell surface EGCG target that plays a pivotal role in tumor growth, metastasis, and resistance to chemotherapy. However, the plasma concentration of EGCG is limited, and its molecular mechanisms remain unelucidated in colon cancer. In this study, we found that the phosphodiesterase 5 (PDE5) inhibitor, vardenafil (VDN), potentiates EGCG-induced apoptotic cell death in colon cancer cells. The combination of EGCG and VDN induced apoptosis via activation of the endothelial nitric oxide synthase/cyclic guanosine monophosphate/protein kinase Cδ signaling pathway. In conclusion, the PDE5 inhibitor, VDN, may reduce the intracellular PDE5 enzyme activity that potentiates EGCG-induced apoptotic cell death in Caco-2 cells. These results suggest that PDE5 inhibitors can be used to elevate cGMP levels to induce 67LR-mediated, cancer-specific cell death. Therefore, EGCG may be employed as a therapeutic candidate for colon cancer.

Original languageEnglish
Pages (from-to)6247-6256
Number of pages10
JournalCurrent Issues in Molecular Biology
Volume44
Issue number12
DOIs
Publication statusPublished - Dec 2022

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology
  • Microbiology (medical)

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