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.