PMID- 30848427
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1873-9601 (Print)
IS  - 1873-961X (Electronic)
IS  - 1873-9601 (Linking)
VI  - 13
IP  - 3
DP  - 2019 Sep
TI  - mTOR inhibitor Everolimus-induced apoptosis in melanoma cells.
PG  - 357-368
LID - 10.1007/s12079-019-00510-0 [doi]
AB  - Melanoma is the most aggressive, therapy-resistant skin cancer. The mammalian 
      target of rapamycin (mTOR), the serine/threonine kinase which integrates both 
      intracellular and extracellular signals, plays a crucial role in coordinating the 
      balance between the growth and death of cells. The object of this study is a 
      comparison of the influence of mTOR inhibitor everolimus in the concentration 
      range between 20 nM and 10 muM, used individually and in combination with selected 
      downstream protein kinases inhibitors: LY294002 (PI3K), U0126 (ERK1/2), AS-703026 
      (MEK) and MK-2206 (AKT) on the expression of pro-survival proteins: p-Bcl-2 
      (S70), p-Bcl-2 (T56), Bcl-2, Bcl-xL, Mcl-1, activity of caspase-3, proliferation 
      and induction of apoptosis in melanoma cells. Current results clearly show that 
      the nanomolar concentration of the mTOR inhibitor everolimus in combination with 
      the inhibitor of MAP kinase (AS-703026) or AKT kinase (MK-2206) is effective in 
      inducing apoptosis and reducing proliferation of melanoma cells. The herein 
      research results confirm the hypothesis on the important role of mTOR signaling 
      in cancer progression, and gives hope that implementation of successful 
      combination of its inhibitors will find recognition and application in cancer 
      treatment in the near future.
FAU - Ciolczyk-Wierzbicka, Dorota
AU  - Ciolczyk-Wierzbicka D
AUID- ORCID: 0000-0003-2631-7308
AD  - Medical Biochemistry, Jagiellonian University Medical College, ul. Kopernika 7, 
      31-034, Krakow, Poland. mbciolcz@cyf-kr.edu.pl.
FAU - Zarzycka, Marta
AU  - Zarzycka M
AD  - Medical Biochemistry, Jagiellonian University Medical College, ul. Kopernika 7, 
      31-034, Krakow, Poland.
FAU - Gil, Dorota
AU  - Gil D
AD  - Medical Biochemistry, Jagiellonian University Medical College, ul. Kopernika 7, 
      31-034, Krakow, Poland.
FAU - Laidler, Piotr
AU  - Laidler P
AD  - Medical Biochemistry, Jagiellonian University Medical College, ul. Kopernika 7, 
      31-034, Krakow, Poland.
LA  - eng
GR  - CCBY/Uniwersytet Jagiellonski Collegium Medicum/
PT  - Journal Article
DEP - 20190308
PL  - Netherlands
TA  - J Cell Commun Signal
JT  - Journal of cell communication and signaling
JID - 101308338
PMC - PMC6732148
OTO - NOTNLM
OT  - Apoptosis
OT  - Caspase-3 activity
OT  - Melanoma
OT  - Proliferation
OT  - Protein kinase inhibitors
OT  - mTOR
COIS- The authors declare that they have no conflict of interest.
EDAT- 2019/03/09 06:00
MHDA- 2019/03/09 06:01
PMCR- 2019/03/08
CRDT- 2019/03/09 06:00
PHST- 2019/02/02 00:00 [received]
PHST- 2019/02/22 00:00 [accepted]
PHST- 2019/03/09 06:00 [pubmed]
PHST- 2019/03/09 06:01 [medline]
PHST- 2019/03/09 06:00 [entrez]
PHST- 2019/03/08 00:00 [pmc-release]
AID - 10.1007/s12079-019-00510-0 [pii]
AID - 510 [pii]
AID - 10.1007/s12079-019-00510-0 [doi]
PST - ppublish
SO  - J Cell Commun Signal. 2019 Sep;13(3):357-368. doi: 10.1007/s12079-019-00510-0. 
      Epub 2019 Mar 8.