TY  - JOUR
A1  - Jüngel, Eva
A1  - Maxeiner, Sebastian
A1  - Rutz, Jochen
A1  - Justin, Saira
A1  - Roos, Frederik
A1  - Khoder, Wael Y.
A1  - Tsaur, Igor
A1  - Nelson, Karen
A1  - Bechstein, Wolf Otto
A1  - Haferkamp, Axel
A1  - Blaheta, Roman A.
T1  - Sulforaphane inhibits proliferation and invasive activity of everolimus-resistant kidney cancer cells in vitro
T2  - OncoTarget
N2  - Although the mechanistic target of rapamycin (mTOR) inhibitor, everolimus, has improved the outcome of patients with renal cell carcinoma (RCC), improvement is temporary due to the development of drug resistance. Since many patients encountering resistance turn to alternative/complementary treatment options, an investigation was initiated to evaluate whether the natural compound, sulforaphane (SFN), influences growth and invasive activity of everolimus-resistant (RCCres) compared to everolimus-sensitive (RCCpar) RCC cell lines in vitro. RCC cells were exposed to different concentrations of SFN and cell growth, cell proliferation, apoptosis, cell cycle, cell cycle regulating proteins, the mTOR-akt signaling axis, adhesion to human vascular endothelium and immobilized collagen, chemotactic activity, and influence on surface integrin receptor expression were investigated. SFN caused a significant reduction in both RCCres and RCCpar cell growth and proliferation, which correlated with an elevation in G2/M- and S-phase cells. SFN induced a marked decrease in the cell cycle activating proteins cdk1 and cyclin B and siRNA knock-down of cdk1 and cyclin B resulted in significantly diminished RCC cell growth. SFN also modulated adhesion and chemotaxis, which was associated with reduced expression of the integrin subtypes α5, α6, and β4. Distinct differences were seen in RCCres adhesion and chemotaxis (diminished by SFN) and RCCpar adhesion (enhanced by SFN) and chemotaxis (not influenced by SFN). Functional blocking of integrin subtypes demonstrated divergent action on RCC binding and invasion, depending on RCC cell sensitivity to everolimus. Therefore, SFN administration could hold potential for treating RCC patients with established resistance towards everolimus.
KW  - renal cell carcinoma
KW  - complementary and alternative medicine
KW  - sulforaphane
KW  - proliferation
KW  - invasion
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45840
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-458404
SN  - 1949-2553
N1  - All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
VL  - 7
IS  - 51
SP  - 85208
EP  - 55219
PB  - Impact Journals LLC
CY  - [S.l.]
ER  -