Shikonin derivatives trigger phenotype reprogramming of B16 mouse melanoma cells
2023
Authors:
Krajnović, TamaraBovan, Dijana
Vuković, Nenad L.
Vukić, Milena D.
Mihajlović, Sanja
Tanić, Nikola
Arsenijević, Nebojša
Maksimović-Ivanić, Danijela
Contributors
Spasojević, IvanDocument Type:
Conference object (Published version)
,
© 2023 by the Faculty of Chemistry, University of Belgrade
Metadata
Show full item recordAbstract:
Shikonin is a naphthoquinone found in the roots of plants of the Boraginaceae family and
is widely known for its numerous biological activities, including anticancer. In this study,
the antitumor mode of action of shikonin derivatives isolated from the roots of Onosma
visianii was investigated in mouse melanoma cell line B16. MTT and CV assays showed
that six examined shikonins decreased B16 cell viability in a dose-dependent manner, with
compounds 5 and 6 exhibiting the highest cytotoxic activity. This effect correlated with
caspase-mediated apoptosis, which was detected by flow cytometry and fluorescence
microscopy. In addition, CFSE staining revealed a strong blockage of cell division in
response to treatment, with a more profound effect of compound 6. The altered cell
morphology together with the loss of dividing potential upon exposure to both shikonins
implied reprogramming of the B16 cell phenotype. The absence of melanogenesis
enhancement coupled with an elevated level of myelin basic protein in response to
treatment with both tested agents suggested that the cells transdifferentiated into a
Schwann-like phenotype, with possible involvement of the autophagic process in this
conversion. Differentiation of malignant cells has become favourable in cancer treatment,
bearing in mind the phenomenon of apoptosis-induced proliferation. Hence, the specific
antitumor mode of action of shikonin derivatives on melanoma in vitro shown here
provides a good platform for new investigations of these promising natural compounds.
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
In:
- Spasojević I, editor. Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia. Belgrade: Faculty of Chemistry; 2023. p. 96.