Journal
ANTICANCER RESEARCH
Volume 39, Issue 7, Pages 3767-3775Publisher
INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.13525
Keywords
Loratadine; azelastine; histamine receptor antagonists; repositioning drug; Cancer; P-gp; drug-resistance
Categories
Funding
- National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2017R1D1A1B03029158]
Ask authors/readers for more resources
Background/Aim: Previously, we showed that KBV20C cancer cells highly resistant to antimitotic drugs were sensitized by co-treatment with a repositioned drug fluphenazine. Materials and Methods: Considering that fluphenazine plays a role as a histamine receptor antagonist, we investigated low doses of 21 other histamine receptor antagonists (lidocaine, cimetidine, chlorpromazine, diphenhydramine, promethazine, ranitidine, famotidine, clemastine, chlorpheniramine, desloratadine, loratadine, cyproheptadine, azelastine, brompheniramine, carbinoxamine, fexofenadine, hydroxyzine, levocetirizine, meclizine, nizatidine, and pemirolast) to identify repositioned drugs for their sensitizing effects on antimitotic drug-resistant KBV20C cells at relatively low doses. Results: Co-treatment with loratadine, and with azelastine highly sensitized KBV20C cells to vincristine treatment. Loratadine and azelastine reduced cell viability, increased G(2) arrest, and up-regulated apoptosis when co-administered with vincristine. In detailed quantitative analysis, combination of vincristine with loratadine had a higher sensitization effect than that with azelastine. Azelastine had a higher P-glycoprotein (P-gp)-inhibitory activity, similar to that of verapamil, indicating that sensitization by vincristine-azelastine involved the P-gp-inhibitory effects of azelastine. However, loratadine had a very low P-gpinhibitory activity, suggesting that loratadine sensitization to vincristine is independent of the P-gp-inhibition. Co-treatment with eribulin and loratadine increased the sensitization of KBV20C cells, suggesting that loratadine can be combined with other antimitotic drugs to sensitize resistant cancer cells. Conclusion: These findings provide important information regarding the sensitization of drug-resistant cells and indicate that loratadine may be used in patients with potentially resistant cancer without any toxic effects from P-gp inhibition.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available