In vitro effect of lupeol derivatives on prostate carcinoma cell lines

MARIA JULIA CASTRO; CAREAGA, VALERIA P.; SACCA, PAULA; CALVO, JUAN C.; ANA PAULA MURRAY; FARAONI, MARÍA BELEN

Punta Cana

Congreso; XXIV Congreso Italo-Latinoamericano de Etnomedicina ?Prof. Eugenio de Jesús Marcano?; 2015

Sociedad Italolatinoamericana de Etnomedicina

Human prostate cancer (PCa) is the most common form of non-cutaneous cancer, and metastatic late-stage PCa represents a significant challenge with few successful treatment options. Statistics shows that PCa is the most common cancer in American men (WHO, 2012). Recent investigations suggest that consumption of fruits, vegetables and medicinal plants rich in triterpenoids, could be beneficial against a variety of diseases, including cancer, due to their ability to target multiple signaling pathways, their cost-effectiveness, and most importantly, their wide acceptance [1]. Lupeol, a pentacyclic triterpenoid, has shown growth inhibition of androgen-responsive and unresponsive human PCa cells lines, without exhibiting toxicity towards normal human prostate epithelial cells [2-3]. Also, novel synthetic triterpenoids which mimic natural ones, have been effective in suppressing inflammation and inducing apoptosis in a wide variety of tumor cells, through diverse mechanisms [4-5].Recently, we have prepared a series of derivatives from natural calenduladiol that were evaluated for its in vitro cytotoxic activity against human tumor cell lines. These studies have revealed that the introduction of sulfate groups enhances cytotoxic activity of these compounds [6]. These results prompted us to synthesize some lupeol derivatives by transformations on C-3. These semisynthetic compounds were evaluated as anti-tumor agents against two human prostate carcinoma cell lines, LNCaP (androgen dependent) and PC-3 (androgen independent). The pharmacological results show that some of these compounds exhibit higher growth inhibition activities than lupeol (IC50 7-42 μM). Both lupeol and calenduladiol were obtained from Chuquiraga erinacea (Asteraceae), an endemic species growing wildly in our region.