Sains Malaysiana 48(2)(2019): 347–352

http://dx.doi.org/10.17576/jsm-2019-4802-11

The Effects of Oleuropein on Apoptotic Rate and Oxidative Stress Profiles during Tumour Promotion Stage in the Mouse Skin Carcinogenesis Model

(Kesan Oleuropein atas Kadar Apoptosis dan Tekanan Oksidatif Profil semasa Peringkat Galakan Tumor dalam Model Karsinogenesis Kulit Tikus)

SITI FATHIAH MASRE*, AZIM IZZUDDEEN, DAYANG NOOR SUZLIANA JOHN & ZARIYANTEY ABDUL HAMID

Biomedical Science Programme, Centre of Health and Applied Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Aziz, 50300 Kuala Lumpur, Federal Territory, Malaysia

Received: 19 February 2018/Accepted: 5 June 2018

ABSTRACT

Oleuropein is a phenolic compound that can be abundantly found in the olive plant and it possesses pharmacological properties including anticancer, antioxidant, and anti-inflammatory. This present study was designed to determine the effects of oleuropein on tumour promotion stage, particularly on the histopathological changes, apoptotic rates and oxidative stress profiles by using the mouse skin carcinogenesis model. Female ICR mice were randomly divided into 3 groups (n= 8 mice per group) as follows: Control induced with DMBA/TPA, negative control (acetone) and oleuropein-treated groups. For the treatment group, the mice were initiated with DMBA (200 nmol) followed by pre-treatment with oleuropein (10 mg/kg) and subsequent promotion with TPA (20 nmol). The treatments were topically applied on the shaved dorsal up to 10 weeks. Histopathology analysis showed that oleuropein-pretreated group appeared lack of thickness in epidermal hyperplasia, as compared to thick hyperplasia and epidermal disorganisation in the DMBA/TPA control group. Data also showed that oleuropein pre-treatment resulted in a significant increase of the apoptotic rates (p<0.05) as indicated by the activated caspase-3 labelling compared to DMBA/TPA group. Interestingly, the level of MDA is significantly reduced (p<0.05) in the oleuropein pre-treated group compared to DMBA/TPA group. Next, pre-treatment of oleuropein caused a significant decrease in the GSH levels (p<0.05) along with a significant increase in the SOD levels (p<0.05) compared to the DMBA/TPA group. Overall, this study indicates that oleuropein may act as a potential chemopreventive agent through its apoptotic and antioxidant defence activities on tumour promotion stage in skin carcinogenesis event.

Keywords: Carcinogenesis; chemoprevention; oleuropein; skin cancer; tumour promotion

ABSTRAK

Oleuropein adalah sebatian fenolik yang banyak ditemui dalam pokok zaitun dan ia mempunyai beberapa aktiviti farmakologi termasuk antikanser, antioksidan dan anti-inflamasi. Kajian ini dijalankan untuk menentukan kesan oleuropein pada peringkat galakan tumor terhadap perubahan histopatologi, kadar apoptosis dan profil tekanan oksidatif dalam model karsinogenesis kulit tikus. Tikus ICR betina dibahagikan secara rawak kepada 3 kumpulan (n= 8 tikus setiap kumpulan): Kawalan induksi dengan DMBA/TPA, kawalan negatif (aseton) dan kumpulan pra-rawatan oleuropein. Bagi kumpulan rawatan, tikus akan diinduksi dengan DMBA (200 nmol) diikuti dengan pra-rawatan oleuropein (10 mg/kg) sebelum diaruh dengan TPA (20 nmol) secara topikal atas bahagian dorsal sehingga 10 minggu. Analisis histopatologi menunjukkan bahawa kumpulan yang dirawat dengan oleuropein kelihatan kekurangan ketebalan epidermis hiperplasia, justeru, menghentikan peringkat galakan tumor berbanding dengan ketebalan hiperplasia dan ketidakaturan susunan epidermis pada kumpulan kawalan DMBA/TPA. Data juga menunjukkan bahawa kumpulan pra-rawatan oleuropein menghasilkan kenaikan signifikan kadar apoptosis (p<0.05) melalui pengaktifan caspase-3 bertanda berbanding kumpulan DMBA/TPA. Menariknya, tahap MDA menunjukkan pengurangan signifikan (p<0.05) dalam kumpulan pra-rawatan oleuropein berbanding kumpulan DMBA/TPA. Seterusnya, pra-rawatan oleuropein menyebabkan penurunan signifikan pada paras GSH (p<0.05) beserta peningkatan signifikan pada paras SOD (p<0.05) berbanding kumpulan DMBA/TPA. Secara keseluruhannya, kajian ini menunjukkan bahawa oleuropein berpotensi bertindak sebagai agen kemohalang melalui aktiviti apoptotik dan pertahanan antioksidan pada peringkat promosi tumor dalam karsinogenesis kulit.

Kata kunci: Kanser kulit; karsinogenesis; kemohalang; oleuropein; promosi tumor

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*Corresponding author; email: sitifathiah@ukm.edu.my