Vincristine promotes differential levels of apoptosis, mitotic catastrophe, and senescence depending on the genetic background of glioblastoma cells

Vincristine (VCR) is a classical chemotherapeutic that has been revisited to treat refractory solid tumors producing encouraging results. VCR binds to tubulin and decreases the rate of microtubule dynamics, thus triggering many cellular responses and behaviors. However, the dynamics of these responses and fates are uncharacterized. This study combined systems biology approaches with acute and long-term in vitro experiments to predict key pathways and mechanisms associated with cell fates during and after VCR treatment. Glioblastoma (GBM) cells were treated with clinically relevant doses of VCR, and interconnected cell fates were explored. A correlation matrix based on experimental cell analysis reported strong negative correlations between cell number, nuclear irregularities, senescence, or apoptosis, depending on the cells' genetic makeup and treatment regimen. P53 would be essential in all analyzed processes according to topological network analysis. Furthermore, despite the high acute sensitivity, both cell lines re-growth in the long term after a single VCR treatment, especially in those populations with high levels of autophagy. These multiple responses may also be triggered in patients' exposed tumors, which should be considered to allow the rational design of VCR protocols, including modulators of the cell fates and pathways mentioned above.