scholarly journals GSK-3β Inhibition Enhances Sorafenib-induced Apoptosis in Melanoma Cell Lines

2007 ◽  
Vol 283 (2) ◽  
pp. 726-732 ◽  
Author(s):  
David J. Panka ◽  
Daniel C. Cho ◽  
Michael B. Atkins ◽  
James W. Mier
Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2012
Author(s):  
Kathryn M. Appleton ◽  
Charuta C. Palsuledesai ◽  
Sean A. Misek ◽  
Maja Blake ◽  
Joseph Zagorski ◽  
...  

The Ras/MEK/ERK pathway has been the primary focus of targeted therapies in melanoma; it is aberrantly activated in almost 80% of human cutaneous melanomas (≈50% BRAFV600 mutations and ≈30% NRAS mutations). While drugs targeting the MAPK pathway have yielded success in BRAFV600 mutant melanoma patients, such therapies have been ineffective in patients with NRAS mutant melanomas in part due to their cytostatic effects and primary resistance. Here, we demonstrate that increased Rho/MRTF-pathway activation correlates with high intrinsic resistance to the MEK inhibitor, trametinib, in a panel of NRAS mutant melanoma cell lines. A combination of trametinib with the Rho/MRTF-pathway inhibitor, CCG-222740, synergistically reduced cell viability in NRAS mutant melanoma cell lines in vitro. Furthermore, the combination of CCG-222740 with trametinib induced apoptosis and reduced clonogenicity in SK-Mel-147 cells, which are highly resistant to trametinib. These findings suggest a role of the Rho/MRTF-pathway in intrinsic trametinib resistance in a subset of NRAS mutant melanoma cell lines and highlight the therapeutic potential of concurrently targeting the Rho/MRTF-pathway and MEK in NRAS mutant melanomas.


2017 ◽  
Vol 404 ◽  
pp. 70-78 ◽  
Author(s):  
Andreas Borst ◽  
Sebastian Haferkamp ◽  
Johannes Grimm ◽  
Manuel Rösch ◽  
Guannan Zhu ◽  
...  

2020 ◽  
Vol 15 (4) ◽  
pp. 1934578X2092232
Author(s):  
Jin Jie Dillon Ng ◽  
Zee Upton ◽  
David Leavesley ◽  
Chen Fan

Melanoma is the most lethal form of various skin cancers and contributes to more than 79% of all skin cancer deaths. Although there are numerous therapies available for melanoma, the high rate of recurrence in melanoma post-therapy remains a challenging issue for both patients and clinicians. Apoptosis is one of the foundations for cancer treatment as deficient apoptosis is one of the most essential reasons for the formation of tumour tissues. Shikonin (SHI), an active component extracted from Lithospermum erythrorhizon, has been broadly demonstrated to possess antitumorigenic property due to its apoptosis-inducing ability in various cancer cell lines. The analogs of SHI, such as deoxyshikonin (DO-SHI) and (β,β-dimethylacryl)shikonin (β,β-SHI), have also been found to possess similar bioactivities. The apoptosis-inducing ability of SHI and its analogs enable them to be potential anticancer therapies. In this study reported herein, we investigated the effects of SHI, DO-SHI, and β,β-SHI on both human (A375) and mouse (B16-F0 and B16-F10) melanoma cell lines. Cell viability was measured using Alamar blue assay, while cell migration was detected using scratch assay. Cell apoptosis was captured using terminal deoxynucleotidyl dUTP nick end labeling and fluorescence activated cell sorting. Signaling pathway activation was detected using Western blotting. Our results revealed that SHI, DO-SHI, and β,β-SHI reduce cell viability, inhibit cell migration, and induce apoptosis in melanoma cell lines. These 3 molecules-induced apoptosis in A375 is regulated via mitogen-activated protein kinase/caspase 3 signaling pathway. In particular, DO-SHI and β,β-SHI induce higher apoptosis rate in A375 and B16-F0 compared to SHI. The data from this study demonstrate that DO-SHI and β,β-SHI offer potential new reagents for managing melanoma.


2003 ◽  
Vol 13 (2) ◽  
pp. 153-159 ◽  
Author(s):  
Takahiko Kamei ◽  
Madoka Inui ◽  
Shinnosuke Nakamura ◽  
Kenya Okumura ◽  
Akira Goto ◽  
...  

2005 ◽  
Vol 15 (2) ◽  
pp. 83-89 ◽  
Author(s):  
Yiqun G. Shellman ◽  
Deborah Ribble ◽  
Leslie Miller ◽  
John Gendall ◽  
Kayleen VanBuskirk ◽  
...  

Biochimie ◽  
2013 ◽  
Vol 95 (4) ◽  
pp. 934-945 ◽  
Author(s):  
Francesco Albano ◽  
Alessandro Arcucci ◽  
Giuseppina Granato ◽  
Simona Romano ◽  
Stefania Montagnani ◽  
...  

2022 ◽  
Vol 23 (2) ◽  
pp. 831
Author(s):  
Jakub Rok ◽  
Zuzanna Rzepka ◽  
Justyna Kowalska ◽  
Klaudia Banach ◽  
Artur Beberok ◽  
...  

Malignant melanoma is still a serious medical problem. Relatively high mortality, a still-growing number of newly diagnosed cases, and insufficiently effective methods of therapy necessitate melanoma research. Tetracyclines are compounds with pleiotropic pharmacological properties. Previously published studies on melanotic melanoma cells ascertained that minocycline and doxycycline exerted an anti-melanoma effect. The purpose of the study was to assess the anti-melanoma potential and mechanisms of action of minocycline and doxycycline using A375 and C32 human amelanotic melanoma cell lines. The obtained results indicate that the tested drugs inhibited proliferation, decreased cell viability, and induced apoptosis in amelanotic melanoma cells. The treatment caused changes in the cell cycle profile and decreased the intracellular level of reduced thiols and mitochondrial membrane potential. The exposure of A375 and C32 cells to minocycline and doxycycline triggered the release of cytochrome c and activated initiator and effector caspases. The anti-melanoma effect of analyzed drugs appeared to be related to the up-regulation of ERK1/2 and MITF. Moreover, it was noticed that minocycline and doxycycline increased the level of LC3A/B, an autophagy marker, in A375 cells. In summary, the study showed the pleiotropic anti-cancer action of minocycline and doxycycline against amelanotic melanoma cells. Considering all results, it could be concluded that doxycycline was a more potent drug than minocycline.


Sign in / Sign up

Export Citation Format

Share Document