The Anti-Proliferative Role of 15,16-Dihydrotanshinone I (DHTS) Extracted from Salvia miltiorrhiza in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Introduction: Autosomal polycystic kidney disease (ADPKD) is a kidney disorder caused by mutations in polycystin proteins resulting in cystic formation in kidney. Tolvaptan, a vasopressin2-receptor (V2R) antagonist, is the only FDA approved drug currently for ADPKD but it demonstrates serious side e...

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Published inAsia-Pacific journal of molecular biology and biotechnology Vol. 29; p. 71
Main Authors Mahendran, Rhubaniya, Lim, Soo Kun, Ong, Kien Chai, Chua, Kek Heng, Chai, Hwa Chia
Format Journal Article
LanguageEnglish
Published Kuala Lumpur Malaysian Society for Molecular Biology and Biotechnology 01.06.2021
Subjects
Assaying
Cancer
Cell proliferation
Cell viability
Cytotoxicity
Hepatocellular carcinoma
Hepatotoxicity
Kidney diseases
Kidneys
Metformin
Mutation
Polycystic kidney
Salvia miltiorrhiza
Side effects
Sulforhodamine
Vasopressin V2 receptors
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Summary:Introduction: Autosomal polycystic kidney disease (ADPKD) is a kidney disorder caused by mutations in polycystin proteins resulting in cystic formation in kidney. Tolvaptan, a vasopressin2-receptor (V2R) antagonist, is the only FDA approved drug currently for ADPKD but it demonstrates serious side effects such as hepatotoxicity. Dihydrotanshinone I (DHTS) extracted from Salvia miltiorrhiza has been shown previously to stop proliferation in cancers. Given that ADPKD also involves cell proliferation, the present study aims to repurpose this natural compound for ADPKD treatment. Methods: The cell viability of ADPKD cells (WT 9-12), normal kidney cells (HK2), and hepatocellular carcinoma cells, (HepG2, positive control cell line) treated with various concentration of DHTS, metformin and tolvaptan (positive control drugs) was assessed using crystal violet viability assay on day 3 and day 6 of treatment. The cells were treated daily (Model 1), every two days (Model 2), and every three days (Model 3). The DHTS concentration(s) that significantly reduced the WT 9-12 cell viability with minimal inhibitory effect on HK2 cells (≤50%) will be further analyzed with sulforhodamine B (SRB) cytotoxic assay and real time cell analyser (RTCA). Results: 5μM (p<0.05) and 10μM (p<0.001) DHTS treatment from Model 2 significantly inhibited the WT 9-12 viability in the preliminary studies with minimal cytotoxic effects on HK2. (SRB assay and RTCA results will be obtained before conference) Conclusion: DHTS showed promising anti-proliferation effects on ADPKD cell in this study. Although the side effects of DHTS is yet to be determined, this natural compound can be gentler alternative than tolvaptan for ADPKD treatment.
ISSN:0128-7451