Caryophyllene Oxide, the Active Compound Isolated from Leaves of Hymenaea courbaril L. (Fabaceae) with Antiproliferative and Apoptotic Effects on PC-3 Androgen-Independent Prostate Cancer Cell Line.

Claudia Delgado,Gina Mendez-Callejas,Crispin Celis

doi:10.3390/molecules26206142

Claudia Delgado, Gina Mendez-Callejas + Show 1 more

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https://doi.org/10.3390/molecules26206142

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Abstract

Cancer treatment frequently carries side effects, therefore, the search for new selective and effective molecules is indispensable. Hymenaea courbaril L. has been used in traditional medicine in South America to treat several diseases, including prostate cancer. Leaves’ extracts from different polarities were evaluated using the 3-(4,5-methyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) cell viability assay to determine the cytotoxicity in prostate p53-null cells, followed by bio-guided fractionations to obtain the most cytotoxic fraction considering the selectivity index. The most cytotoxic fraction was analyzed by GC/MS to identify the active compounds. The majority compound, caryophyllene oxide, induced early and late apoptosis, depolarized the mitochondrial membrane, leading to several morphological changes and shifts in apoptotic proteins, and caspases were evidenced. Depolarization of the mitochondrial membrane releases the pro-apoptotic protein Bax from Bcl-xL. The apoptosis process is caspase-7 activation-dependent. Caryophyllene oxide is a safe anti-proliferative agent against PC-3 cells, inducing apoptosis with low toxicity towards normal cells.

Highlights

Prostate cancer (PC) has become a leading cause of cancer-related death in men all over the world
Most PCs are usually acinar adenocarcinomas characterized by glandular formation, absence of basal cells, uncontrolled proliferation of tumor cells, and expression of differentiation luminal markers, such as the androgen receptor (AR) and the prostate-specific antigen (PSA), and the majority of these adenocarcinomas are androgendependent, which allows hormone therapy that inhibits AR signaling [1,2,3,4]
This study aimed to evaluate the antiproliferative effect of extracts and fractions, and the apoptotic effect of the major secondary metabolite from the leaves of the plant Hymenaea courbaril in androgen-independent prostate cancer cells, PC-3, and contribute to its ethnobotanical knowledge

Summary

Introduction

Prostate cancer (PC) has become a leading cause of cancer-related death in men all over the world. There are variant forms of prostatic epithelial malignancies, such as the Small-Cell Neuroendocrine Carcinoma (SCNC), which are rare tumors that account for no more than 1% of all prostate carcinomas [5,6]. They are often seen as recurrent tumors in patients who have received hormone therapy and become resistant to hormone-suppressive therapy [2,4,5]. SCNC is considered a lethal disease without effective treatment options other than chemotherapy [2,4]

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