Euphol arrests breast cancer cells at the G1 phase through the modulation of cyclin D1, p21 and p27 expression

Abstract

Abstract. Euphorbia tirucalli is a long-established treatment for a wide variety of cancers. However, the mechanism of its anticancer effect is yet to be elucidated. In the present study, we examined the anticancer effect of euphol, a tetracyclic triterpene alcohol isolated from the sap of Euphorbia tirucalli, in T47D human breast cancer cells. Following the treatment of cells with different doses of euphol for 24, 48 and 72 h, the cell proliferation, cell cycle, and mRNA and protein levels of cell cycle regulatory molecules were analyzed, respectively. Treatment of the cells with euphol resulted in decreased cell viability, which was accompanied by an accumulation of cells in the G1 phase. Further studies demonstrated that euphol treatment downregulated cyclin D1 expression and the hypophosphorylation of Rb. Furthermore, this effect was correlated with the downregulation of cyclin-dependent kinase 2 (CDK2) expression and the upregulation of the CDK inhibitors p21 and p27. Reduced expression levels of cyclin A and B1 were also observed, corresponding to the decreased distribution of cells in the S and G2/M phases, respectively. These findings indicated that euphol is an active agent in Euphorbia tirucalli that exerts anticancer activity by arresting the cell cycle of cancer cells.

Effect of crude latex from Euphorbia tirucalli on DMBA-induced carcinogenesis

“…The crude latex from E. tirucalli is used in traditional medicine [3,5,29] for the treatment of several types of cancer [5,6]. In the present study, no significant differences were found between the different substances used regarding the anticarcinogenic effect on the oral mucosa after 13 and 20 weeks.…”

“…In other in vitro studies, euphol, which is a triterpene alcohol isolated from E. tirucalli, demonstrated high cytotoxicity to cancer cells. The authors suggest that euphol inhibits cyclins involved in the cell cycle and upregulates pro-apoptotic proteins [5,6,31].…”

“…The latex from this species is commonly used in traditional medicine [3] for the treatment of cancer [2,[4][5][6][7]. This substance is also reported to have immunomodulatory [7,8], analgesic [9], angiogenic [10], antimicrobial [11], antimutagenic and antirheumatic [12] properties.…”

CDK/CCN and CDKI Alterations for Cancer Prognosis and Therapeutic Predictivity

“…Euphol treatment downregulated CCND1 expression and the hypophosphorylation of Rb. Furthermore, this effect was correlated with the downregulation of CDK2 expression and the upregulation of the CDKIs (CDKN1A and CDKN1B), as well as reduced expression levels of CCNA and CCNB1 [105]. Treatment options for hepatocellular carcinoma (HCC) using chemotherapeutics at intermediate and advanced stages of disease are limited as frequently HCC escape from therapy and patients succumb to disease progression.…”

Antimicrobial Activity of two Semisynthetic Triterpene Derivatives from Euphorbia Officinarum Latex Against Fungal and Bacterial Phytopathogens

“…Euphorbia includes plants that are characterized by the presence of latex containing triterpenic compounds such as euphol and euphorbol [6] with anti-inflammatory [7], antitumor [8], antileishmanial [9] and antimicrobial activity against human pathogens [10,11]. However, a preliminary study of the antimicrobial activity of lupeol acetate, 31-norlanostenol and euphorbol against several fungal and bacterial phytopathogens did not show any noticeable activity.…”