Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells

Autor:	Javier Alejandro Belmont-Díaz, Sara Rodríguez-Enríquez, Víctor M. Dávila-Borja, Juan Carlos Gallardo-Pérez, Betsy Alejandra Blanco-Carpintero, Rafael Moreno-Sánchez, Silvia Cecilia Pacheco-Velázquez, Stephen John Ralph, Diana Xochiquetzal Robledo-Cadena
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	dimethylcelecoxib lcsh:Medicine lcsh:RS1-441 Pharmaceutical Science Pharmacology Article lcsh:Pharmacy and materia medica HeLa resistance index chemistry.chemical_compound Therapeutic index Drug Discovery medicine Doxorubicin HeLa cells IC50 Cisplatin drug synergism biology celecoxib lcsh:R biology.organism_classification Paclitaxel chemistry Cancer cell Bliss-type additivism model Celecoxib Molecular Medicine medicine.drug
Zdroj:	Pharmaceuticals Volume 13 Issue 12 Pharmaceuticals, Vol 13, Iss 463, p 463 (2020)
ISSN:	1424-8247
DOI:	10.3390/ph13120463
Popis:	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 (&ldquo preventive protocol&rdquo IC50 = 1 ± 0.3 nM for celecoxib and 10 ± 2 nM for DMC) or after spheroid formation (&ldquo curative protocol&rdquo IC50 = 7.5 ± 2 µ M for celecoxib and 32 ± 10 µ M for DMC). These NSAID IC50 values were significantly lower than those attained in bidimensional HeLa cells (IC50 = 55 ± 9 µ M celecoxib and 48 ± M DMC) and bidimensional non-cancer cell cultures (3T3 fibroblasts and MCF-10A mammary gland cells with IC50 from 69 to > 100 µ M, 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&ndash 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.
Databáze:	OpenAIRE
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