Mechanistic investigations of antitumor activity of a Rhodamine B‑oleanolic acid derivative bioconjugate.

Abstract

Cancer remains a major health problem worldwide due to its high mortality rate. New therapeutic options highlight the importance of discovering new compounds that target the tumor microenvironment, interrupt angiogenesis and act selectively. The present study assessed the antitumor effect and investigated the mechanism of action of a rhodamine B-conjugated oleanolic acid derivative (RhodOA). Consequently, the compound was tested on different human tumor cell lines (A375 melanoma, A549 lung adenocarcinoma and MDA-MB-231 breast adenocarcinoma) and on a non-tumor cell line HaCaT human keratinocyte. RhodOA produced a dose-dependent decrease in tumor cell viability especially in the melanoma cells while affecting the keratinocytes less. In melanoma cells, RhodOA reduced cell migration and produced condensation of cell nuclei and of actin fibers. Furthermore, an impairment in melanoma cell mitochondrial function was observed, while the mitochondrial function of keratinocytes was left intact. In the in ovo chorioallantoic membrane model, RhodOA elicited antiangiogenic effect, without showing irritation effect on the membrane. The study provides information on the selective antitumor effect of the derivative and its ability to inhibit cellular respiration, therefore RhodOA can be classified as ‘MITOCAN’.