Altertoxin ii, a highly effective and specific compound against ewing sarcoma

Andrew J. Robles, Wentao Dai, Saikat Haldar, Hongyan Ma, Victoria M. Anderson, Ross D. Overacker, April L. Risinger, Sandra Loesgen, Peter J. Houghton, Robert H. Cichewicz, Susan L. Mooberry

Resultado de la investigación: Articlerevisión exhaustiva

4 Citas (Scopus)


A screening program designed to identify natural products with selective cytotoxic effects against cell lines representing different types of pediatric solid tumors led to the identification of altertoxin II as a highly potent and selective cytotoxin against Ewing sarcoma cell lines. Altertoxin II, but not the related compounds altertoxin I and alteichin, was highly effective against every Ewing sarcoma cell line tested, with an average 25‐fold selectivity for these cells as compared to cells representing other pediatric and adult cancers. Mechanism of action studies revealed that altertoxin II causes DNA double‐strand breaks, a rapid DNA damage response, and cell cycle accumulation in the S phase. Our studies also demonstrate that the potent effects of altertoxin II are partially dependent on the progression through the cell cycle, because the G1 arrest initiated by a CDK4/6 inhibitor decreased antiproliferative potency more than 10 times. Importantly, the cell‐typeselective DNA‐damaging effects of altertoxin II in Ewing sarcoma cells occur independently of its ability to bind directly to DNA. Ultimately, we found that altertoxin II has a dose‐dependent in vivo antitumor efficacy against a Ewing sarcoma xenograft, suggesting that it has potential as a therapeutic drug lead and will be useful to identify novel targets for Ewing‐sarcoma‐specific therapies.

Idioma originalEnglish (US)
Número de artículo6176
EstadoPublished - dic 1 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Profundice en los temas de investigación de 'Altertoxin ii, a highly effective and specific compound against ewing sarcoma'. En conjunto forman una huella única.

Citar esto