Labd-14-ene-8,13-diol (sclareol) induces cell cycle arrest and apoptosis in human breast cancer cells and enhances the activity of anticancer drugs

Cancer cell spheroids as a model to evaluate chemotherapy protocols

“…8,43 While sclareol did not promote doxorubicin accumulation, it increased its toxicity. A synergistic action of sclareol and doxorubicin has been demonstrated with monolayers, 27 and our results support the existence of this synergy using three-dimensional cultures.…”

“…38 Synergy between doxorubicin and sclareol was demonstrated in vitro after their co-administration. 27 We obtained a similar LDH release with the three sequences, suggesting that the interaction between these two antineoplastic agents is not schedule-dependent. The higher LDH release observed after co-administration of doxorubicin and methotrexate contradicts reports on the absence of any benefit of methotrexate addition in doxorubicin treatment of sarcoma.…”

“…25,49 In conclusion, this study strengthens the likelihood that spheroids can be used to adequately assess drug combinations as the schedule-dependencies observed for dexamethasone, cisplatin and paclitaxel were in agreement with the data from clinical studies 16,37,38,47 and in accordance with in vitro studies for sclareol and dexamethasone. 27,44 Finally, the different efficacies obtained with drug combinations including free, micellar or liposomal doxorubicin and the cancer cell-specific antibody binding to spheroids open opportunities for the testing of tumor-targeted drug formulations in spheroid models. Monoclonal cancer-specific antinuclear autoantibody 2C5 was produced by Harlan Bioproducts using a hybridoma cell line from our laboratory.…”

“…6,15,25,26 We evaluated combinations of clinically relevant drugs belonging to different groups: mitoxantrone (anthracenedione), cisplatin (alkylating-like), dexamethasone (glucocorticosteroid), methotrexate (antifolate), sclareol (labdane diterpene), paclitaxel (taxane) and doxorubicin (anthracycline). In vitro use of these drugs in combination protocols was reported for sclareol and methotrexate, 27,28 in vivo for paclitaxel, cisplatin and dexamethasone; 8,[29][30][31] and with patients for doxorubicin, paclitaxel, mitoxantrone and methotrexate. [16][17][18][32][33][34] Their sequential combination with doxorubicin in a spheroid model was studied in this report.…”

Crude ethyl acetate extract of marine microalga,Chaetoceros calcitrans, induces Apoptosis in MDA-MB-231 breast cancer cells

“…This effect was suggested to be dose-dependent and was irreversible at the high concentration. [21] The cell population of sub-G1 was significantly induced by the CEA extract at the high concentration (120 μg/mL), in which the irreparable DNA underwent fragmentation. [22,23] These results imply that the CEA extract would be useful for the suppression of cell proliferation, with a cytostatic effect at lower concentrations (30 and 60 μg/mL), although a cytotoxic effect was induced at the high concentration (120 μg/mL).…”