Cell lines

myeloma cell lines (JK-6L, RPMI8226, and ARH-77 cell lines)

Preparation method

The solubility of this compound in DMSO is >14.5mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

70 μM; 16 h

Applications

In myeloma cell lines, the combination of bortezomib (10 nM) and verapamil (70 μM) markedly reduced the viability of the JK-6L, RPMI8226, and ARH-77 cell lines. JK-6L cells were more sensitive toward bortezomib and verapamil treatment. Combination of bortezomib and verapamil might induce predominantly apoptotic cell death and activation of caspase 3/7.

Animal models

The collagen-induced arthritis (CIA) mice model

Dosage form

20 mg/kg; intraperitoneally every day starting on day 21

Application

In CIA mice model, verapamil remarkably attenuated development of arthritis and alleviated inflammation. Verapamil also significantly reduced mRNA levels of inflammation-associated molecules, including IL-1β, IL-6, NOS-2, and COX-2.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Verapamil hydrochloride is a calcium channel antagonist.

Verapamil (hydrochloride) is an L-type calcium channel antagonist. The combination of Bortezomib and Verapamil (70 μM) markedly declines the viability of the JK-6L, RPMI 8226, and ARH-77 cell lines after 16 hours of culture[1]. The enzyme hydrolase activity of recombinant human carboxylesterase (CES2) is substantially inhibited by Verapamil with Ki of 3.84±0.99μM[2].

Verapamil, a calcium channel antagonist, is injected i.v. into a femoral vein prior to ischemia. Verapamil (1 mg/kg) significantly decreases the incidence of ventricular arrhythmias including premature ventricular contractions (PVC), ventricular tachycardia (VT) and ventricular fibrillation (VF) for 45-min coronary artery occlusion. Total arrhythmia scores are significantly increased when the heart is subjected to ischemia (P<0.01 vs. sham). Verapamil (1 mg/kg) significantly prevented the enhancement of total arrhythmia scores induced by ischemia (P<0.01 vs. ischemia). Results indicate that Verapamil exerts an anti-arrhythmic property[3].

References:
[1]. Meister S, et al. Calcium channel blocker Verapamil enhances endoplasmic reticulum stress and cell death induced by proteasome inhibition in myeloma cells. Neoplasia. 2010 Jul;12(7):550-61.
[2]. Yanjiao X, et al. Evaluation of the inhibitory effects of antihypertensive drugs on human carboxylesterase in vitro. Drug Metab Pharmacokinet. 2013;28(6):468-74.
[3]. Zhou P, et al. Anti-arrhythmic effect of Verapamil is accompanied by preservation of cx43 protein in rat heart. PLoS One. 2013 Aug 12;8(8):e71567.