Autophagic cell death and premature senescence: New mechanism of 5-fluorouracil and sulforaphane synergistic anticancer effect in MDA-MB-231 triple negative breast cancer cell line
2018
Milczarek, Malgorzata | Wiktorska, Katarzyna | Mielczarek, Lidia | Koronkiewicz, Mirosława | Dąbrowska, Aleksandra | Lubelska, Katarzyna | Matosiuk, Dariusz | Chilmonczyk, Zdzisław
In view of the need for new, more effective therapies for the triple negative breast cancer treatment, the aim of the study was to evaluate the anticancer activity and mechanism of action of the sulforaphane and 5-fluorouracil combination in the triple negative breast cancer cell line MDA-MB-231.Changes in the number of live cells after alone and sequential treatment were determined by the MTT test. The Chou and Talaly method was used to identify the type of interaction. Confocal microscopy, flow cytometry, western blot and spectrophotometry were used to examine apoptosis, autophagy and premature senescence. The western blot method was applied to measure the level of enzymes that are crucial for the 5-fluorouracil activity.Sulforaphane and 5-fluorouracil have been shown to interact synergistically in the breast cancerMDA-MB-231 cell line, resulting in a significant reduction of the number of live cells compared to alone treatments. Sulforaphane has decreased the level of thymidylate synthetase, which was also observed in the case of the sequential sulforaphane and 5-fluorouracil treatment. Studies of the interaction mechanism have revealed that sulforaphane and 5-fluorouracil act synergistically in the MDA-MB-231 cells by inducing autophagic cell death and premature senescence.
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