mTOR inhibitor Everolimus-induced apoptosis in melanoma cells.

mTOR inhibitor Everolimus-induced apoptosis in melanoma cells.

Publication date: Mar 08, 2019

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 μM, 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.

Ciolczyk-Wierzbicka, D., Zarzycka, M., Gil, D., and Laidler, P. mTOR inhibitor Everolimus-induced apoptosis in melanoma cells. 21907. 2019 J Cell Commun Signal.

Concepts Keywords
AKT Apoptosis
AKT Kinase Apoptosis
Apoptosis Protein kinase B
Caspase 3 MTOR inhibitors
ERK1 Immunosuppressants
Everolimus Programmed cell death
Extracellular Oncology
Inhibitor Antineoplastic drugs
Intracellular Signal transduction
Kinase Enzymes
MAP Kinase Medicine
MEK Branches of biology
Melanoma Resistant skin cancer
MTOR Proliferation melanoma
Nanomolar Activity Melanoma
PI3K
Rapamycin
Serine
Skin Cancer
Threonine

Semantics

Type Source Name
disease DOID cancer
disease MESH cancer
gene UNIPROT SGSM3
gene UNIPROT MCL1
gene UNIPROT BCL2
gene UNIPROT AKT1
gene UNIPROT MAP2K7
gene UNIPROT MAPK3
gene UNIPROT PIK3CG
gene UNIPROT PIK3CB
gene UNIPROT PIK3CD
gene UNIPROT PIK3CA
disease MESH death
disease MESH growth
drug DRUGBANK Isoxaflutole
drug DRUGBANK L-Threonine
drug DRUGBANK Serine
gene UNIPROT MTOR
drug DRUGBANK Sirolimus
disease DOID skin cancer
disease MESH skin cancer
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
pathway BSID Apoptosis
drug DRUGBANK Everolimus

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