Synergistic interactions of cytarabine-adavosertib in leukemic cell lines proliferation and metabolomic endpoints

Marine-Derived Anticancer Agents Targeting Apoptotic Pathways: Exploring the Depths for Novel Cancer Therapies

“…The key challenge to cytarabine therapy and chemotherapeutic approaches continued to be the compound 1 resistance of AML cells. Reducing the expression of the G2/M checkpoint kinase Wee-1 (Wee1) in AML cells is an important target mechanism to mitigate cancer resistance and DNA repair [ 70 ]. Adavosertib and other Wee1 inhibitors functioned as the main source of interference for the delayed G2/M transition, which in turn caused the induction of apoptosis [ 70 ].…”

“…Reducing the expression of the G2/M checkpoint kinase Wee-1 (Wee1) in AML cells is an important target mechanism to mitigate cancer resistance and DNA repair [ 70 ]. Adavosertib and other Wee1 inhibitors functioned as the main source of interference for the delayed G2/M transition, which in turn caused the induction of apoptosis [ 70 ]. Interestingly, in the Jurkat acute lymphoblastic leukemia (ALL) animal system, the therapeutic combination of 1 and adavosertib changed important metabolic pathways [ 70 ].…”

“…Adavosertib and other Wee1 inhibitors functioned as the main source of interference for the delayed G2/M transition, which in turn caused the induction of apoptosis [ 70 ]. Interestingly, in the Jurkat acute lymphoblastic leukemia (ALL) animal system, the therapeutic combination of 1 and adavosertib changed important metabolic pathways [ 70 ]. The primary enriched processes, such as the mitochondrial electron transport chain, gluconeogenesis, and Krebs cycle, were disrupted with this combinatorial pharmacological treatment [ 70 ].…”

“…Interestingly, in the Jurkat acute lymphoblastic leukemia (ALL) animal system, the therapeutic combination of 1 and adavosertib changed important metabolic pathways [ 70 ]. The primary enriched processes, such as the mitochondrial electron transport chain, gluconeogenesis, and Krebs cycle, were disrupted with this combinatorial pharmacological treatment [ 70 ]. Collectively, the synergistic pharmacological interaction of 1 with adavosertib provided a more mechanistic understanding of 1 ’s impact on all cell apoptosis, proliferation, and cancer development [ 70 ].…”

“…The primary enriched processes, such as the mitochondrial electron transport chain, gluconeogenesis, and Krebs cycle, were disrupted with this combinatorial pharmacological treatment [ 70 ]. Collectively, the synergistic pharmacological interaction of 1 with adavosertib provided a more mechanistic understanding of 1 ’s impact on all cell apoptosis, proliferation, and cancer development [ 70 ]. Even with the previously described antiAML characteristics, cytarabine administration in adult fruit flies was found to cause intestinal cell damage in a recent study [ 71 ].…”