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Vincarubine: Unraveling a cytotoxic mechanism against cancer cells

Authors: Koutova Darja | Abdul Aziz Timbilla Abdul Aziz Timbilla | Královec Karel | Jan Korabecny | Martina Rezacova | Lucie Cahlikova | Rudolf Vrabec | Radim Havelek

Year: 2024

Type of publication: ostatní - přednáška nebo poster

Page from-to: nestránkováno

Titles:

Language	Name	Abstract	Keywords
eng	Vincarubine: Unraveling a cytotoxic mechanism against cancer cells	The naturally occurring monoterpene bis indole alkaloids vincristine and vinblastine are well known and established chemotherapeutics used in the conventional treatment of certain types of cancer. They act as cytotoxic agents mainly by disrupting microtubule dynamics in cells. Another naturally occurring alkaloid with a similar structure, vincarubine, has been isolated from aerial parts of Vinca minor in this study . Given its structure similarity, an initial screening of vincarubine's cytostatic and cytotoxic activity on a panel of nine tumor an d one non tumor cell lines was performed. Vincarubine significantly inhibited cell growth at 10 uM, more so than the positive standard doxorubicine at 1  M. The IC 50 values for these cell lines were determined with a average of 3.5  M. These results encouraged a deeper focus on its mechanism of action. The effects of vincarubine on cell viability and proliferation in A549, MCF 7, A2780, and MRC 5 cell lines were further studied using xCELLigence method in real time. The impact on the cell cycle in A549 cell line suggested that vincarubine perturbs proliferation in the G1 phase, contrary to vincristine. The docking study into the active site of tubulin showed weaker interaction as well, implying the involvement of different mechanisms. The study on activation of caspase 3 and 7 indicated that vincarubine induces apoptosis, particularly in Jurkat and SAOS 2 cell lines, at concentrations of 5 and 10  M. Additionally, vincarubine influence on the level and organisation of proteins such as actin, tubulin, paxilli n, and vinculin was determined through epifluorescence imaging of A549 cells, further suggesting a distinct mechanism of action from vincristine and vinblastine. This study highlights the importance of exploring naturally occurring compounds for cancer therapy, as evidenced by vincarubine's specific mechanism of action and its potential to offer a new therapeutic approach.	vincarubine; cytotoxic mechanism; cancer; cells