Toxicity and Apoptosis Related Effects of Benzimidazo [3,2-α] Quinolinium Salts Upon Human Lymphoma Cells



Christian Vélez1, Jessica Soto1, Karoline Ríos1, Luz Silva2, Wigberto Hernandez3, Luis A. Rivera4, Ana I. Ortiz-Colón5, Osvaldo Cox1, Beatriz Zayas1, *
1 Universidad Metropolitana, School of Environmental Affairs, San Juan, Puerto Rico
2 Institute of Biomedical and Forensic Sciences Research of Puerto Rico, San Juan, Puerto Rico
3 Department of Chemistry University of Puerto Rico, San Juan, Puerto Rico
4 Department of Chemistry, University of Puerto Rico at Mayaguez, San Juan, Puerto Rico
5 Department of Anatomy and Neurobiology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico


Article Metrics

CrossRef Citations:
0
Total Statistics:

Full-Text HTML Views: 1747
Abstract HTML Views: 578
PDF Downloads: 307
ePub Downloads: 159
Total Views/Downloads: 2791
Unique Statistics:

Full-Text HTML Views: 487
Abstract HTML Views: 266
PDF Downloads: 196
ePub Downloads: 115
Total Views/Downloads: 1064



© 2017 Vélez et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this authors at the School of Environmental Affairs, Universidad Metropolitana, PO Box 21150 San Juan, Puerto Rico, 00926, Tel: 787-766-1717, Ext 6460, 6412, E-mail: bzayas@suagm.edu


Abstract

Objectives:

The present study evaluates novel cationic quinoline derivatives known as benzimidazo[3,2-a]quinolinium salts (BQS) named NBQ-48 and ABQ-48 that have structural similarities to known anti-cancer substances such as ellipticine and berberine.

Methods:

Toledo human lymphoma (ATCC CRL2631) cells were treated for 24 to 48 hours. Apoptosis related endpoints such as cell cycle arrest, mitochondrial damage, RNS and ROS generation and the activity of several apoptosis related proteins such as caspases and apoptosis inducing factor (AIF) were studied using fluorescence staining and western blot respectively.

Results:

Results indicated a higher toxicity from the amino substituted ABQ-48 versus the NBQ-48 (GI50’s of 50uM versus 100uM respectively). Both compounds induced cell death through various apoptosis related endpoints including a decrease in mitochondrial membrane potential with an increase in ROS and activation of the effector caspase 3. Interestingly, AIF release was observed on cells treated with the amino substituted ABQ-48 but not on the nitro substituted NBQ-48 samples suggesting a caspase independent mechanism for ABQ-48.

Conclusions:

The results obtained presents the toxic effects of two novel benzimidazo[3,2-a]quinolinium salts in human lymphoma tumor cells. The identified mechanism of action includes multiple apoptosis related effects. Furthermore the data presents a clear variation in caspase dependent or independent mechanism for each compound.

Keywords: Benzimidazo[3,2-a]quinolinium Salts, BQS, Apotosis, Apoptosis Inducing Factor, Anti cancer, Unnatural alkaloid, Diffuse large B-cell Lymphoma.