Synthetic Tubulysin Derivative, Tubugi-1, Against Invasive Melanoma Cells: The Cell Death Triangle.
2019
Authors:
Drača, DijanaMijatović, Sanja
Krajnović, Tamara
Kaluđerović, Goran N
Wessjohann, Ludger A
Maksimović-Ivanić, Danijela
Document Type:
Article (Published version)
,
© 2019 International Institute of Anticancer Research
Metadata
Show full item recordAbstract:
BACKGROUND/AIM Tubugi-1 is a more stable and accessible synthetic counterpart of natural tubulysins. This study aimed to evaluate its cytotoxic potential against anaplastic human melanoma cells. MATERIALS AND METHODS The viability of A-375 cells was determined by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet assay. The type of cell death and proliferative rate were investigated using flow cytometry and fluorescent microscopy, while the molecular background was evaluated by western blot. RESULTS Tubugi-1 reduced the viability of A-375 cells, inducing massive micronucleation, followed by augmented expression of inhibitor of nuclear factor-κB and caspase-2, typical of a mitotic catastrophe. Disturbed proliferation and G2M block with prominent caspase activity, weakened the expression of B-cell lymphoma 2 and B-cell lymphoma 2-associated X transient up-regulation, coexisted with intensive autophagy. Specific inhibition of autophagy by chloroquine resulted in conversion from mitotic catastrophe to rapid apoptosis. CONCLUSION Multilevel anticancer action of tubugi-1 is extended by co-application of an autophagy inhibitor, giving a new dimension in further preclinical advancement of this potential agent.
Keywords:
Tubugi-1; Apoptosis; Autophagy; Melanoma; Mitotic catastropheSource:
Anticancer Research, 2019, 39, 10, 5403-5415Funding / projects:
- Cellular and molecular mechanisms of recovery of rats from experimental autoimmune encephalomyelitis (RS-MESTD-Basic Research (BR or ON)-173035)
- Molecular mechanisms of physiological and pharmacological control of inflammation and cancer (RS-MESTD-Basic Research (BR or ON)-173013)
- Deutscher Akademischer Austauschdienst
- Institut Pertanian Bogor
DOI: 10.21873/anticanres.13734
PubMed: 31570435
WoS: 000488512600015
Scopus: 2-s2.0-85072777864
URI
https://radar.ibiss.bg.ac.rs/handle/123456789/3484http://ar.iiarjournals.org/content/39/10/5403