Type II topoisomerases (TOP2s) can alter DNA topology. And it plays an important role in replication, transcription, recombination, and chromosome condensation and segregation.
Passage of a second DNA segment through this enzyme-bridged “DNA gate”. What’s more, TOP2’s DNA cleavage activity is a double-edged sword. The failure of TOP2-mediated DNA would lead to cell death.
In this article, we will introduce a potent anti-cancer chemotherapy agent, Etoposide.
Etoposide inhibits topoisomerase II, thus stopping DNA replication. In vitro, in RIN-m5F cells, Etoposide is capable of causing cytotoxicity on pancreatic β-cells by inducing apoptosis. And it play its role through the JNK/ERK-mediated GSK-3 downstream-triggered mitochondria-dependent signaling pathway.
Additionally, In different cancer cells, Etoposide inhibits HCT116 FBXW+/+, FBXW-/- and p53-/- as a dose-dependent manner. The IC50 values are 0.945 μM; 0.375 μM; and 1.437 μM, respectively.
Metastatic melanoma is a kind of aggressive skin cancer, exhibiting high resistance to chemotherapy. Indeed, the presence of cancer stem cells (CSCs) causes cancer resistance to chemotherapy.
The CSCs constitute a pool of self-renewing cells and has the ability to sustain tumor growth. Additionally, symmetric division of CSCs allows cell population expansion while maintaining their distinctive traits.
There exists evidence that supports the presence of CSCs in several malignancies, including blood, brain, breast and, melanoa.
Etoposide is a cytostatic agent acting through apoptotic mechanisms. Besides, Etoposide has frequent use in lung cancer, leukemia, and testicular tumors.
In FBXW7-deficient cells, Etoposide delays p53 recovery. Additionally, FBXW7 expression is disappeared in FBXW7-/- cells.
In vitro, Etoposide and Anti-Human VEGF significantly abolish P1 sphere-forming ability, an effect associated with apoptosis of this subset of cells.
When Etoposide and Anti-Human VEGF-treated hypoxic cells inject intravenously into immunodeficient mice. The mice reveal a reduced capacity to induce lung colonies, which also appear with a longer latency period. Furthermore, Etoposide with NSC 109724 and NSC 241240, reduces the tumor volume in the hepatoblastoma cell injected NMRI nude mice.
In conclusion, Etoposide is a potent anti-cancer chemotherapy agent. It plays its anti-cancer role in vitro and in vivo.
. Lee KI, et al. Toxicol In Vitro. 2016 Jul 26. pii: S0887-2333(16)30147-3.
. Calvani M, det al. Oncotarget. 2016 Jun 9. doi: 10.18632/oncotarget.9939.