Caffeic Acid Phenethyl Ester (CAPE) Induced Apoptosis in Serous Ovarian Cancer OV7 Cells by Deregulation of BCL2/BAX Genes.

Anna Kleczka,Krzysztof Jasik,Robert Kubina,Radosław Dzik,Krzysztof Cholewa,Agata Kabała-Dzik,Jerzy Stojko

doi:10.3390/molecules25153514

Anna Kleczka, Krzysztof Jasik + Show 5 more

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https://doi.org/10.3390/molecules25153514

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Abstract

Ovarian cancer has the worst prognosis among all gynecological cancers. Therefore, it seems reasonable to seek new drugs that may improve the effectiveness of treatment or mitigate the adverse effects of chemotherapy. Caffeic acid phenethyl ester (CAPE) has many beneficial biological properties. The aim of the study was to assess the anticancer properties of CAPE against serum ovarian carcinoma cells. The morphology of the cells was evaluated in H-E staining and in transmission electron microscopy. The cytotoxic and proapoptotic activity of CAPE was investigated by using the XTT-NR-SRB assay, qRT-PCR analysis of BAX/BCL2 expression, and by cytometric evaluation. CAPE causes constriction in OV7 cells, numerous granulomas were observed in the cytoplasm, the cell nuclei were pyknotic. Autophagosomal vacuoles could suggest the occurrence of aponecrosis. CAPE significantly decreased the lysosomal activity and the total synthesis of cellular proteins. CAPE exhibited, dose and time dependent, cytotoxic activity against OV7 serum ovarian cancer cells. In OV7 cells CAPE induced apoptosis via dysregulation of BAX/BCL2 balance, while activated proapoptotic BAX gene expression level was 10 times higher than BCL2.

Highlights

Caffeic acid phenethyl ester (CAPE) is a bioactive compound produced as a secondary metabolite by most plants
Studying the ratio of BAX/BCL2 genes, we found that the use of CAPE strongly enhances the activity of the proapoptotic gene in OV7 cells, while the expression of the gene synthesizing the antiapoptotic protein was present, but 10 times lower
The cytotoxic activity of CAPE depends on its concentration and incubation time with the OV7 cells

Summary

Introduction

Caffeic acid phenethyl ester (CAPE) is a bioactive compound produced as a secondary metabolite by most plants. Literature data indicate that CAPE presents a number of antimicrobial, antioxidant, anti-inflammatory, immunomodulatory and cytotoxic properties [1,2,3]. Researchers have proven that CAPE is a therapeutically versatile polyphenol and an effective chemotherapy adjuvant. The administration of CAPE in order to increase therapeutic efficacy and reduce chemotherapy-induced toxicity may find wide application in the treatment of many cancers [4]. The mechanism of CAPE antitumor activity is based on the inhibition of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells). NF-κB is a protein transcription factor that affects the activity of crucial proto-oncogenes and promotes the growth and survival of altered cells during the cell cycle [5,6]

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