UNBS1450 from Calotropis procera as a regulator of signaling pathways involved in proliferation and cell death

Abstract

Despite significant progress in oncology therapeutics in the last decades, the urge to discover and to develop new, alternative or synergistic anti-cancer agents still remains. For centuries it has been known that the coarse shrub Calotropis procera is a very promising source of ascaricidal, schizonticidal, anti-bacterial, anthelmintic, insecticidal, anti-inflammatory, anti-diarrhoeal, larvicidal and cytotoxic chemicals. Different compounds like norditerpenic esters, organic carbonates, the cysteine protease procerain, alkaloids, flavonoids, sterols as well as numerous types of cardenolides have provided this plant for centuries with scientists' interest. The chemical class of cardenolides and their related bioactivity evaluation and structure-activity relationship (SAR) studies pointed out their therapeutic utility and led to the discovery of promising drug candidates. Recently the cardiotonic steroid UNBS1450 01 (derived from 2-oxovoruscharin 02) from C. procera was shown to additionally exert an anti-cancer activity. UNBS1450 01 has been proven to be a potent sodium pump inhibitor, showing anti-proliferative and cell death-inducing activities. This anti-cancer potential of UNBS1450 01 is achieved by disorganization of the actin cytoskeleton after binding to the sodium pump at the cellular membrane, by inducing autophagy-related cell death, by repressing NF-kappaB activation as well as by down-regulating c-Myc in cancer cells. We aim to review pharmacologically important chemical extracts from C. procera and focus more specifically on the anti-cancer activities of UNBS1450 01.

Anti-cancer potential of South Asian plants

“…To reveal the probable phyto-chemicals responsible for anti-cancer effect, focus has been directed towards heat-stable latex proteins from C. procera due to its inhibitory activities on sarcoma 180 growth 37 . On the other hand, studies have also emphasized non-protein phyto-constituent such as the cardiotonic steroid UNBS1450 (8) from C. procera that additionally exert anticancer activity by cytoskeleton disorganization, autophagyrelated cell death induction, NF-κB activation repression as well as c-Myc down-regulation in cancer cells 38 .…”

Cytotoxic Cardenolides from Calotropis Species: A Short Review

“…Chemical modification of 2´´-oxovoruscharin, a novel cardenolide isolated from the root bark of C. procera, has led to the synthesis of UNBS1450, a compound characterized by more potent antiproliferative activity and lower toxicity [55,64,65]. The compound displayed anti-tumour activity against a panel of 57 human cancer cell lines that is comparable to taxol, and stronger than SN-38, two of the most potent drugs used in hospitals to treat cancer [55].…”

“…This non-apoptotic cancer cell death mediated by nucleolar targeting and down-regulation of c-Myc expression is a new mechanism of anti-tumour action. Through disorganization of the actin cytoskeleton, the compound possesses both anti-proliferative and antimigratory properties [55,64,65]. UNBS1450 has shown to be a potent sodium pump inhibitor and induces non-apoptotic cell death.…”

Anticancer Herbs in Ayurveda: A Review

“…Calotropis procera: In a recent study the cardiotonic steroid UNBS1450 01 (derived from 2-oxovoruscharin 02) from C. procera was shown to additionally exert an anti-cancer activity. UNBS1450 01 has been proven to be a potent sodium pump inhibitor, showing antiproliferative and cell death-inducing activities 34 .…”