Rosamines targeting the cancer oxidative phosphorylation pathway. Academic Article uri icon


  • Reprogramming of energy metabolism is pivotal to cancer, so mitochondria are potential targets for anticancer therapy. A prior study has demonstrated the anti-proliferative activity of a new class of mitochondria-targeting rosamines. This present study describes in vitro cytotoxicity of second-generation rosamine analogs, their mode of action, and their in vivo efficacies in a tumor allografted mouse model. Here, we showed that these compounds exhibited potent cytotoxicity (average IC50<0.5 M), inhibited Complex II and ATP synthase activities of the mitochondrial oxidative phosphorylation pathway and induced loss of mitochondrial transmembrane potential. A NCI-60 cell lines screen further indicated that rosamine analogs 4 and 5 exhibited potent antiproliferative effects with Log10GI50=-7 (GI50=0.1 M) and were more effective against a colorectal cancer sub-panel than other cell lines. Preliminary in vivo studies on 4T1 murine breast cancer-bearing female BALB/c mice indicated that treatment with analog 5 in a single dosing of 5 mg/kg or a schedule dosing of 3 mg/kg once every 2 days for 6 times (q2d6) exhibited only minimal induction of tumor growth delay. Our results suggest that rosamine analogs may be further developed as mitochondrial targeting agents. Without a doubt proper strategies need to be devised to enhance tumor uptake of rosamines, i.e. by integration to carrier molecules for better therapeutic outcome.

published proceedings

  • PLoS One

author list (cited authors)

  • Lim, S. H., Wu, L., Kiew, L. V., Chung, L. Y., Burgess, K., & Lee, H. B.

citation count

  • 13

complete list of authors

  • Lim, Siang Hui||Wu, Liangxing||Kiew, Lik Voon||Chung, Lip Yong||Burgess, Kevin||Lee, Hong Boon

editor list (cited editors)

  • Pandey, S.

publication date

  • March 2014