Inhibition by verapamil of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats

Abstract

Summary The effect of verapamil on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) was investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and received i.p. injections of verapamil or vehicle every other day for 16 weeks from the start of the experiment.Pre-neoplastic and neoplastic lesions staining positive for y-glutamyl transpeptidase (GGT) or the placental type of glutathione-S-transferase (GST-P) were examined histochemically at week 16. Prolonged administration of verapamil resulted in a significant decrease in the number of GGT-positive and GST-P-positive lesions. The incidence and volume as a percentage of parenchyma of hepatocellular carcinomas were also significantly less in rats treated with verapamil than in controls. Administration of verapamil significantly decreased the labelling indices of pre-neoplastic lesions and adjacent liver. These findings indicate that verapamil inhibits hepatocarcinogenesis and that this may be related to its inhibitory effect on cell proliferation in neoplastic lesions and surrounding hepatocytes.

Long-term use of calcium channel blocking drugs and breast cancer risk in a prospective cohort of US and Puerto Rican women

“…However, in-vivo studies and animal models have shown inconsistent relationships between calcium channel blocking drugs and apoptosis; treatment with the drugs promotes apoptosis in some cancerous and noncancerous cell types and reduces apoptosis in others [ 23 – 29 ]. In fact, calcium channel blocking drugs appear to have antitumorigenic properties in some situations [ 30 – 33 ]. This lack of convincing biological evidence is consistent with the observed lack of association between calcium channel blocker use and breast cancer risk in this study.…”

Chromatographic Separation of Verapamil Racemate Using a Varicol Continuous Multicolumn Process

“…S-(-)-VER is 10-20 times more potent than R-(+)-VER in slowing the cardiac A-V conduction velocity in humans, dogs and rabbits (Lankford and Bai, 1995;Mateus et al, 2007). Although R-(+)-VER has been shown to have lower antiarrhythmic potency, studies have found that this enantiomer has anti-tumor activity (Uehara et al, 1993;Warmann et al, 2002).…”

Effects of calcium channel blockers on cellular apoptosis

“…20 -26 Moreover, CCBs have been shown to inhibit cell growth and metastasis in various models of neoplasia, including breast carcinoma. [27][28][29][30][31][32][33][34] The carcinogenic potential of CCBs has also been rigorously evaluated in whole animals with fully integrated systems. These animal genotoxicity studies have demonstrated unequivocally that there is not a link between CCB use and tumor development in animals, even at highly elevated drug concentrations administered over an extended period of time.…”