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- Title
d-a-Tocopheryl Polyethylene Glycol 1000 Succinate and a small-molecule Survivin suppressant synergistically induce apoptosis in SKBR3 breast cancer cells.
- Authors
Neophytou, Christiana M.; Mesaritis, Avgoustinos; Gregoriou, Gregoria; Constantinou, Andreas I.
- Abstract
Breast cancer is the second in mortality rate malignancy among women. Despite the many advances in breast cancer treatment, there is still a need to improve drug efficacy and reduce non-specific effects. D-alpha-tocopheryl polyethylene glycol succinate (TPGS) is frequently used in the development of drug delivery systems to improve the pharmacokinetics of anti-cancer drugs and reduce multi-drug resistance. We have previously shown that TPGS not only acts as a carrier molecule but also exerts anti-cancer effects. As part of this study, we investigated the effect of TPGS with YM155, a small molecule suppressant of Survivin, in various breast cancer cell lines representing different subtypes of the disease. We aimed to evaluate the presumed synergistic effect of the TPGS-YM155 combination and reveal its mechanism of action. Our results show that the TPGS-YM155 combination acts synergistically to reduce specifically the viability of SKBR3 cells. The combination of these agents reduced activation of the AKT pathway, decreased Survivin and Bcl-2 levels, and induced caspase-dependent and independent apoptosis via the mitochondrial pathway. Importantly, the TPGS-YM155 combination did not significantly affect the viability of MCF-10A normal immortalized cells. In conclusion, the combination of YM155 and TPGS could be a promising approach against SKBR3-type breast cancer.
- Subjects
POLYETHYLENE glycol; SURVIVIN (Protein); APOPTOSIS; BREAST cancer treatment; DRUG efficacy
- Publication
Scientific Reports, 2019, Vol 9, Issue 1, pN.PAG
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-019-50884-9