Description
Etoposide is a derivative of epipodophyllotoxin that acts as an anticancer chemotherapeutic and immunomodulatory compound, inhibiting DNA topoisomerase II and preventing DNA repair. In breast cancer cells, etoposide increases phosphorylation of p38 MAPK and CHK2 and decreases expression of fragile histidin triad (FHIT), causing cell death. In hepatoma cells, etoposide induces mixed modes of programmed cell death, including both autophagy and apoptosis. In leukemia cells, etoposide increases transcription of PKCδ. Etoposide is also used to treat hemophagocytic lymphohistiocytosis (HLH), in which it decreases release of pro-inflammatory cytokines and inhibits activated T cells, increasing survival rates.
References
Johnson TS, Terrell CE, Millen SH, et al. Etoposide selectively ablates activated T cells to control the immunoregulatory disorder hemophagocytic lymphohistiocytosis. J Immunol. 2014 Jan 1;192(1):84-91. PMID: 24259502.
Mir Mohammadrezaei F, Mohseni kouchesfehani H, Montazeri H, et al. Signaling crosstalk of FHIT, CHK2 and p38 in etoposide induced growth inhibition in MCF-7 cells. Cell Signal. 2013 Jan;25(1):126-32. PMID: 23000346.
Yoo SH, Yoon YG, Lee JS, et al. Etoposide induces a mixed type of programmed cell death and overcomes the resistance conferred by Bcl-2 in Hep3B hepatoma cells. Int J Oncol. 2012 Oct;41(4):1443-54. PMID: 22895528.
Shin SY, Kim CG, Ko J, et al. Transcriptional and post-transcriptional regulation of the PKC delta gene by etoposide in L1210 murine leukemia cells: implication of PKC delta autoregulation. J Mol Biol. 2004 Jul 16;340(4):681-93. PMID: 15223313.
Mizumoto K, Rothman RJ, Farber JL. Programmed cell death (apoptosis) of mouse fibroblasts is induced by the topoisomerase II inhibitor etoposide. Mol Pharmacol. 1994 Nov;46(5):890-5. PMID: 7969076.
Nissen NI, Dombernowsky P, Hansen HH, et al. The epipodophyllotoxin derivatives VM-26 and VP-16-213, 1976-1979, a review. Recent Results Cancer Res. 1980;74:98-106. PMID: 7003663.
