Oxalomalate reduces tumor progression in melanoma via ROS-dependent proapoptotic and antiangiogenic effects.

In this study, we investigated the therapeutic effects of OMA in melanoma and elucidated the associated underlying mechanisms of action using in vitro and in vivo models. OMA targeting IDH enzymes suppressed melanoma growth through activation of apoptosis and inhibition of angiogenesis. Mechanistically, our findings showed that OMA activated p53-mediated apoptosis through ROS-dependent ATM-Chk2 signaling and reduced the expression of vascular endothelial growth factor through ROS-dependent E2F1-mediated hypoxia inducible factor-1α degradation. In particular, OMA-induced suppression of IDH activity resulted in induction of ROS stress response, ultimately leading to apoptotic cell death and antiangiogenic effects in melanoma cells. Thus, OMA might be a potential candidate drug for melanoma skin cancer therapy.
PMID: 30639360 [PubMed - as supplied by publisher]

Source: Biochimie - January 9, 2019 Category: Biochemistry Authors: Kim SH, Kil IS, Kwon OS, Kang BS, Lee DS, Lee HS, Lee JH, Park JW Tags: Biochimie Source Type: research