Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro
2024
Аутори:
Bovan, DijanaKrajnović, Tamara
Vuković, Nenad L.
Vukić, Milena D.
Mijatović, Sanja
Tanić, Nikola
Arsenijević, Nebojša
Maksimović-Ivanić, Danijela
Тип документа:
Чланак у часопису (Објављена верзија)
,
© The Author(s), under exclusive licence to Springer Nature B.V. 2024
Метаподаци
Приказ свих података о документуАпстракт:
Background: Shikonin is a naturally occurring naphthoquinone found in the roots of several genera of the Boraginaceae family, widely known for its numerous biological activities, such as antiinflammatory, antioxidant, antimicrobial and anticancer. In this study, the antitumor effect of six naphthoquinones isolated from the roots of Onosma visianii was evaluated using two cell lines, mouse melanoma B16 and highly aggressive rat glioma cell line C6.
Methods and results: All examined shikonins dose-dependently decreased the viability of tested cells, with compounds 5 and 6 being the most potent ones and hence subjected to further analysis. The diminished viability of B16 melanoma cells was in correlation with detected caspase-mediated apoptosis. Importantly, observed altered cell morphology along with the loss of dividing potential upon exposure to both shikonins implied reprogram of B16 cell phenotype. Elevated expression of myelin basic protein indicated the acquirement of Schwann‐like cell phenotype, while detected autophagy might be connected to this phenomenon. On the contrary, upon exposure to both agents, C6 cells underwent specific cell death—anoikis, provoked by detachment from the extracellular matrix and compromised integrin signaling. Oppositely to compound 5, compound 6 realized anoikis in a caspase-independent manner and under sustained ERK1/2 activation, indicating the deviation from standard proanoikis signaling.
Conclusions: Herein, we have pointed out the diversity and novelty in the mode of action of shikonin derivatives depending on the tumor cell features, which represents a good platform for new investigations of these promising natural compounds.
Кључне речи:
Shikonins; Melanoma; Glioma; Differentiation; AnoikisИзвор:
Molecular Biology Reports, 2024, 51, 1, 218-Финансирање / пројекти:
- Joint funding of Development and research projects of the Republic of Serbia and the People’s Republic of China [Grant Number No. 06/2018]
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
DOI: 10.1007/s11033-023-09093-x
ISSN: 0301-4851
PubMed: 38281240