Research articles
ScienceAsia 51 (2023): 1-10 |doi:
10.2306/scienceasia1513-1874.2023.044
Metabolites of lansoprazole inhibit CFTR-mediated Cl-
transport and retard cyst progression
Kanlayanee Tonuma,b, Punyawee Jintanapanyac,d, Nipitpon Srimaid, Napason Chabange,
Sunhapas Soodvilaid,f,*
ABSTRACT: Polycystic kidney disease (PKD) is a genetic disorder that results in renal cyst formation and cyst
enlargement. PKD causes abnormal cell proliferation and fluid secretion in the cyst which results in a loss of normal
function and eventually leads to renal failure. A previous study reported the beneficial effect of lansoprazole, a proton
pump inhibitor, on cyst progression in vitro and renal cyst progression in PKD rats. The present study investigated
whether the major metabolites of lansoprazole, lansoprazole sulfide, and lansoprazole sulfone affected the progression
of microcysts derived from the Madin Darby canine kidney (MDCK) cells. The results showed that treatment of the
MDCK cells with lansoprazole sulfide or lansoprazole sulfone increased the expression of sterol regulatory element
binding protein-1c (SREBP-1c), a target protein of the liver X receptor. Lansoprazole sulfide or lansoprazole sulfone
significantly inhibited cystic fibrosis transmembrane conductance regulator (CFTR)-mediated Cl? secretion compared
with vehicle-treating cells. However, they did not affect calcium-activated chloride channel (CaCC)-mediated Cl
secretion. Incubation of MDCK-derived cysts with lansoprazole sulfide or lansoprazole sulfone for 3 and 6 days led
to a decrease in the growth of the cysts without affecting the viability of the cells. In addition, lansoprazole sulfide
significantly reduced the number of forskolin-induced cysts, but lansoprazole sulfone had no effect. The inhibitory
effect of lansoprazole sulfide on cyst formation was related to reduced cell proliferation. This finding is the first in vitro
evidence supporting that the metabolites of lansoprazole could inhibit Cl? secretion and suppress cyst progression of
the renal collecting duct cells.
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| a |
Department of Physiology, Faculty of Pharmacy, Mahidol University, Bangkok 10400 Thailand |
| b |
Centre of Biopharmaceutical Science for Healthy Ageing, Faculty of Pharmacy, Mahidol University,
Bangkok 10400 Thailand |
| c |
Toxicology Graduate Program, Multidisciplinary Unit, Faculty of Science, Mahidol University,
Bangkok 10400 Thailand |
| d |
Research Center of Transporter Protein for Medical Innovation, Department of Physiology, Faculty of Science,
Mahidol University, Bangkok 10400 Thailand |
| e |
School of Bioinnovation and Bio-Based Product Intelligence, Faculty of Science, Mahidol University,
Bangkok 10400 Thailand |
| f |
Excellent Center for Drug Discovery, Mahidol University, Bangkok 10400 Thailand |
* Corresponding author, E-mail: sunhapas.soo@mahidol.ac.th
Received 17 Jun 2024, Accepted 10 Mar 2025
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