Robledo-Cadena 2020 Pharmaceuticals (Basel)

Robledo-Cadena DX, Gallardo-Pérez JC, Dávila-Borja V, Pacheco-Velázquez SC, Belmont-Díaz JA, Ralph SJ, Blanco-Carpintero BA, Moreno-Sánchez R, Rodríguez-Enríquez S (2020) Non-steroidal anti-inflammatory drugs increase cisplatin, paclitaxel, and doxorubicin efficacy against human cervix cancer cells. Pharmaceuticals (Basel) 13:463.

» PMID: 33333716 Open Access

Robledo-Cadena Diana Xochiquetzal, Gallardo-Perez Juan Carlos, Davila-Borja Victor, Pacheco-Velazquez Silvia Cecilia, Belmont-Diaz Javier Alejandro, Ralph Stephen John, Blanco-Carpintero Betsy Alejandra, Moreno-Ssnchez Rafael, Rodriguez-Enriquez Sara (2020) Pharmaceuticals (Basel)

Abstract: This study shows that the non-steroidal anti-inflammatory drug (NSAID) celecoxib and its non-cyclooxygenase-2 (COX2) analogue dimethylcelecoxib (DMC) exert a potent inhibitory effect on the growth of human cervix HeLa multi-cellular tumor spheroids (MCTS) when added either at the beginning ("preventive protocol"; IC₅₀ = 1 ± 0.3 nM for celecoxib and 10 ± 2 nM for DMC) or after spheroid formation ("curative protocol"; IC₅₀ = 7.5 ± 2 µM for celecoxib and 32 ± 10 µM for DMC). These NSAID IC₅₀ values were significantly lower than those attained in bidimensional HeLa cells (IC₅₀ = 55 ± 9 µM celecoxib and 48 ± 2 µM DMC) and bidimensional non-cancer cell cultures (3T3 fibroblasts and MCF-10A mammary gland cells with IC₅₀ from 69 to >100 µM, after 24 h). The copper-based drug casiopeina II-gly showed similar potency against HeLa MCTS. Synergism analysis showed that celecoxib, DMC, and casiopeinaII-gly at sub-IC₅₀ doses increased the potency of cisplatin, paclitaxel, and doxorubicin to hinder HeLa cell proliferation through a significant abolishment of oxidative phosphorylation in bidimensional cultures, with no apparent effect on non-cancer cells (therapeutic index >3.6). Similar results were attained with bidimensional human cervix cancer SiHa and human glioblastoma U373 cell cultures. In HeLa MCTS, celecoxib, DMC and casiopeina II-gly increased cisplatin toxicity by 41-85%. These observations indicated that celecoxib and DMC used as adjuvant therapy in combination with canonical anti-cancer drugs may provide more effective alternatives for cancer treatment. • Keywords: Bliss-type additivism model, HeLa cells, Celecoxib, Dimethylcelecoxib, Drug synergism, Resistance index • Bioblast editor: Plangger M • O2k-Network Lab: MX Mexiko City Moreno-Sanchez R

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Cancer 

Organism: Human  Tissue;cell: Endothelial;epithelial;mesothelial cell, HeLa, Fibroblast  Preparation: Intact cells 

Coupling state: LEAK 

HRR: Oxygraph-2k 

2021-01