Eugenol Exerts Apoptotic Effect and Modulates the Sensitivity of HeLa Cells to Cisplatin and Radiation.

Moustafa Fathy,Eman M Othman,Thomas Dandekar,Toshio Nikaido,Michael Atef Fawzy,Henning Hintzsche

doi:10.3390/molecules24213979

Moustafa Fathy, Eman M Othman + Show 4 more

Open Access

https://doi.org/10.3390/molecules24213979

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Abstract

Eugenol is a phytochemical present in different plant products, e.g., clove oil. Traditionally, it is used against a number of different disorders and it was suggested to have anticancer activity. In this study, the activity of eugenol was evaluated in a human cervical cancer (HeLa) cell line and cell proliferation was examined after treatment with various concentrations of eugenol and different treatment durations. Cytotoxicity was tested using lactate dehydrogenase (LDH) enzyme leakage. In order to assess eugenol’s potential to act synergistically with chemotherapy and radiotherapy, cell survival was calculated after eugenol treatment in combination with cisplatin and X-rays. To elucidate its mechanism of action, caspase-3 activity was analyzed and the expression of various genes and proteins was checked by RT-PCR and western blot analyses. Eugenol clearly decreased the proliferation rate and increased LDH release in a concentration- and time-dependent manner. It showed synergistic effects with cisplatin and X-rays. Eugenol increased caspase-3 activity and the expression of Bax, cytochrome c (Cyt-c), caspase-3, and caspase-9 and decreased the expression of B-cell lymphoma (Bcl)-2, cyclooxygenase-2 (Cox-2), and interleukin-1 beta (IL-1β) indicating that eugenol mainly induced cell death by apoptosis. In conclusion, eugenol showed antiproliferative and cytotoxic effects via apoptosis and also synergism with cisplatin and ionizing radiation in the human cervical cancer cell line.

Highlights

Current cancer treatments are very efficient drugs, yet these medications result in a number of serious side effects [1,2]
The present study investigates the molecular mechanism of eugenol underlying its antiproliferative effects on human cervical cancer cells (HeLa cells) and their increase in sensitivity to common therapies
The proliferation was expressed as a percentage relative to that of cells cultured in medium only

Summary

Introduction

Current cancer treatments are very efficient drugs, yet these medications result in a number of serious side effects [1,2]. In the search for novel therapies, one promising approach is the use of natural compounds that stop, delay, or reverse the initiation and progression of carcinogenesis. Some of these agents act synergistically with established cytostatic drugs or radiation and can be considered chemo- and/or radio-sensitizers [3,4]. Eugenol showed antioxidant activity at low concentrations; at high concentrations, it enhanced the generation of free radicals acting as a pro-oxidant, leading to cell death [13]. It was reported that eugenol affected the metabolic profile of normal human oral cells in vitro and caused cellular damage for hepatocytes isolated from rats [14,15]. Eugenol at high concentrations was observed to increase the DNA breaks in normal human fibroblast cells [16]

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