Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo.
2019
Аутори:
Paskaš, SvetlanaMazzon, Emanuela
Basile, Maria Sofia
Cavalli, Eugenio
Al-Abed, Yousef
He, Mingzhu
Rakočević, Sara
Nicoletti, Ferdinando
Mijatović, Sanja
Maksimović-Ivanić, Danijela
Тип документа:
Чланак у часопису (Рецензирана верзија)
,
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Метаподаци
Приказ свих података о документуАпстракт:
We generated a nitric oxide (NO)-releasing derivative of the anti-HIV protease inhibitor lopinavir by linking the NO moiety to the parental drug. We investigated the effects of lopinavir and its derivative lopinavir-NO on melanoma cell lines in vitro and in vivo. Lopinavir-NO exhibited a twofold stronger anticancer action than lopinavir in vitro. These results were successfully translated into syngeneic models of melanoma in vivo, where a significant reduction in tumour volume was observed only in animals treated with lopinavir-NO. Both lopinavir and lopinavir-NO inhibited cell proliferation and induced the trans-differentiation of melanoma cells to Schwann-like cells. In melanoma cancer cell lines, both lopinavir and lopinavir-NO induced morphological changes, minor apoptosis and reactive oxygen species (ROS) production. However, caspase activation and autophagy were detected only in B16 cells, indicating a cell line-specific treatment response. Lopinavir-NO released NO intracellularly, and NO neutralization restored cell viability. Treatment with lopinavir-NO induced only a transient activation of Akt and inhibition of P70S6 kinase. The results of this study identify lopinavir-NO as a promising candidate for further clinical trials in melanoma and possibly other solid tumours.
Кључне речи:
HIV protease inhibitors; Lopinavir; Melanoma; Nitric oxide; Schwann-like cells; Trans-differentiationИзвор:
Investigational New Drugs, 2019Финансирање / пројекти:
- Молекуларни механизми физиолошке и фармаколошке контроле инфламације и канцера (RS-MESTD-Basic Research (BR or ON)-173013)
- IRCCS Centro Neurolesi “Bonino–Pulejo”, Messina, Italy
DOI: 10.1007/s10637-019-00733-3
PubMed: 30706336
WoS: 000486034100020
Scopus: 2-s2.0-85060929429
URI
http://link.springer.com/10.1007/s10637-019-00733-3https://radar.ibiss.bg.ac.rs/handle/123456789/3261