[Retracted] Ginsenoside Rg3 Alleviates Antithyroid Cancer Drug Vandetanib‐Induced QT Interval Prolongation

Abstract

Inhibition of human ether-a-go-go-related gene (hERG) potassium channel is responsible for acquired long QT syndromes, which leads to life-threatening cardiac arrhythmia. A multikinase inhibitor, vandetanib, prolongs the progression-free survival time in advanced medullary thyroid cancer. However, vandetanib has been reported to induce significant QT interval prolongation, which limits its clinical application. Some studies have showed that ginsenoside Rg3 decelerated hERG K(+) channel tail current deactivation. Therefore, in this study, we aim to confirm whether ginsenoside Rg3 targeting hERG K(+) channel could be used to reverse the vandetanib-induced QT interval prolongation. Electrocardiogram (ECG) and monophasic action potential (MAP) were recorded using electrophysiology signal sampling and analysis system in Langendorff-perfused rabbit hearts. The current clamp mode of the patch-clamp technique was used to record transmembrane action potential. The whole-cell patch-clamp technique was used to record the hERG K+ current. In Langendorff-perfused hearts, vandetanib prolonged the QT interval in a concentration-dependent manner with an IC50 of 1.96 μmol/L. In human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), vandetanib significantly prolonged the action potential duration at 50%, 70%, and 90% repolarization (APD50, APD70, and APD90). In stable transfected human hERG gene HEK293 cells, vandetanib caused concentrate-dependent inhibition in the step and tail currents of hERG. As expected, ginsenoside Rg3 relieved vandetanib-induced QT interval prolongation in Langendorff-perfused heart and reversed vandetanib-induced APD prolongation in hiPSC-CMs. Furthermore, ginsenoside Rg3 alleviated vandetanib-induced hERG current inhibition and accelerated the process of the channel activation. Ginsenoside Rg3 may be a promising cardioprotective agent against vandetanib-induced QT interval prolongation through targeting hERG channel. These novel findings highlight the therapeutic potential of ginsenoside to prevent vandetanib-induced cardiac arrhythmia.

Exploration of the Use of Natural Compounds in Combination with Chemotherapy Drugs for Tumor Treatment

“…Ginsenoside Rg3, a tetracyclic triterpene saponin extracted from Red ginseng, has been shown to selectively inhibit tumor cell invasion and metastasis [ 115 ]. However, a study on the QT prolongation induced by the anti-thyroid cancer drug vandetanib showed that ginsenoside Rg3 combined with vandetanib could increase the inactivating current of hERG Kchannel, thereby reversing the QT prolongation [ 116 ].…”

Acacetin Alleviates Cardiac Fibrosis via TGF-β1/Smad and AKT/mTOR Signal Pathways in Spontaneous Hypertensive Rats

“…Western blot analysis was performed to detect the protein expression with the protocol as described previously [11]. Briefly, total protein was extracted by using RIPA lysis buffer containing protease inhibitors for 15~20 min from ventricular tissues of WKY, SHR, or human fibroblasts.…”

Ginsenoside Rh1 regulates gastric cancer cell biological behaviours and transplanted tumour growth in nude mice via the TGF‐β/Smad pathway

“…Meyer, possess a plethora of pharmacological properties 7 . Moreover, ginsenosides have been reported to confer anti‐tumour effects in a variety of cancers including gastrointestinal cancer, non‐small cell lung cancer, and thyroid cancer 8–10 . Ginsenoside Rh1 is one of the main bioactive compounds extracted from red ginseng, and recent investigations have suggested that Rh1 as a traditional medicine monomer is capable of exerting certain antitumor properties 11,12 .…”

“…7 Moreover, ginsenosides have been reported to confer anti-tumour effects in a variety of cancers including gastrointestinal cancer, non-small cell lung cancer, and thyroid cancer. [8][9][10] Ginsenoside Rh1 is one of the main bioactive compounds extracted from red ginseng, and recent investigations have suggested that Rh1 as a traditional medicine monomer is capable of exerting certain antitumor properties. 11,12 What is more, ginsenoside Rh1 was previously associated with a blockade of cell migration and invasion in breast cancer and colorectal cancer.…”