Caffeic Acid Phenethyl Ester Increases Radiosensitivity of Estrogen Receptor-Positive and -Negative Breast Cancer Cells by Prolonging Radiation-Induced DNA Damage

Abstract

PurposeBreast cancer is an important cause of death among women. The development of radioresistance in breast cancer leads to recurrence after radiotherapy. Caffeic acid phenethyl ester (CAPE), a polyphenolic compound of honeybee propolis, is known to have anticancer properties. In this study, we examined whether CAPE enhanced the radiation sensitivity of MDA-MB-231 (estrogen receptor-negative) and T47D (estrogen receptor-positive) cell lines.MethodsThe cytotoxic effect of CAPE on MDA-MB-231 and T47D breast cancer cells was evaluated by performing an 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. To assess clonogenic ability, MDA-MB-231 and T47D cells were treated with CAPE (1 µM) for 72 hours before irradiation, and then, a colony assay was performed. A comet assay was used to determine the number of DNA strand breaks at four different times.ResultsCAPE decreased the viability of both cell lines in a dose- and time-dependent manner. In the clonogenic assay, pretreatment of cells with CAPE before irradiation significantly reduced the surviving fraction of MDA-MB-231 cells at doses of 6 and 8 Gy. A reduction in the surviving fraction of T47D cells was observed relative to MDA-MB-231 at lower doses of radiation. Additionally, CAPE maintained radiation-induced DNA damage in T47D cells for a longer period than in MDA-MB-231 cells.ConclusionOur results indicate that CAPE impairs DNA damage repair immediately after irradiation. The induction of radiosensitivity by CAPE in radioresistant breast cancer cells may be caused by prolonged DNA damage.

Anticancer Activity in Honeybee Propolis: Functional Insights to the Role of Caffeic Acid Phenethyl Ester and Its Complex With γ-Cyclodextrin

“…It is known for a variety of effects of which anticancer is well established by laboratory studies. 21 - 27 Some unfavorable characteristics of propolis include high viscosity, pungent taste, poor solubility in water, sensitivity to light and heat because of high polyphenol content, and low bioavailability. Furthermore, CAPE, a major anticancer bioactive in propolis, has been reported to be heat-sensitive and easily degradable.…”

“…Although both kinds of propolis have been demonstrated to possess similar activities, CAPE has been shown to possess pronounced antiproliferative, proapoptotic, antimicrobial, and antioxidative activities. 21 - 25 We have recently shown that the CAPE possesses anticancer and antimetastasis activities, and its complex with γ-cyclodextrin (γCD) further enhances anticancer potential. 26 In the present study, we report that CAPE is effective for a variety of cell lines.…”

Comparison of Two Components of Propolis: Caffeic Acid (CA) and Caffeic Acid Phenethyl Ester (CAPE) Induce Apoptosis and Cell Cycle Arrest of Breast Cancer Cells MDA-MB-231

“…Furthermore, the DNA destruction in T47D cells took longer than in MDA-MB-231 cells, when the irradiation assisted with CAPE treatment was performed. They put forth the thesis that CAPE prolonged DNA damage that could induce the radiosensitivity in the breast carcinoma cells [ 44 ].…”

Therapeutic Properties of Bioactive Compounds from Different Honeybee Products

“…Moreover, CAPE seems synergistic with tamoxifen on MCF-7 breast cancer cells (Motawi et al, 2016), and has induced radiosensitivity on MDA-MB-231 (estrogen receptor negative) and T47D (estrogen receptor positive) breast cancer cell lines (Khoram et al, 2016). …”