Sains Malaysiana 46(9)(2017): 1499–1503

http://dx.doi.org/10.17576/jsm-2017-4609-19

Role of Cytochrome P450 Monooxygenase in the Bioactivation of Aflatoxin B1

(Peranan Sitokrom P450 Monooksigenase dalam Biopengaktifan Aflatoksin B1)

SUREEPORN NUALKAEW, HIRUN SAELIM, DANAI TIWAWECH, TANATE PANRAT IMRAN PARVEZ & AMORNRAT PHONGDARA*

Center for Genomics and Bioinformatics Research, Department of Molecular Biotechnology

and Bioinformatics, Faculty of Science, Prince of Songkla University, Hatyai,

Songkhla 90112, Thailand

Diserahkan: 31 Ogos 2016/Diterima: 17 Januari 2017

ABSTRACT

In a previous study, the gene EgP450 that encodes the proteins of 505 amino acids was isolated from oil palm. The recombinant protein EgP450 is bound to phenylurea-like herbicides which detoxify the substance. Aflatoxin B1 (AFB1), a mycotoxin produced by Aspergillus sp., is another toxic compound that is known to cause acute toxic effects and act as a hepatocarcinogenic agent. This study aimed to examine the role of EgP450 enzyme in mycotoxin bioactivation in human mesenchymal stem cells (hMSCs). Docking analysis showed that EgP450 is bound to the group of carcinogens, which includes AFB1, n-(2-fluorenyl) acetamide, n-n-butyl-n-butan-4-ol-nitrosamine, n-nitrosodiethylamine, n-nitrosodiethylamine and n-nitrosodimethylamine. An in vivo aflatoxin toxicity test on hMSCs and AFB1 induces the expression of Bmi_-1 which is one of the markers for the development of cancer. The presence of EgP450 at 0.15 μg/mL could reduced the Bmi_-1 expression in AFB1 induced cells. Moreover, this protein also showed some antioxidant activity. These results exhibited the enormous potential of EgP450 in the detoxification processes.

Keywords: Carcinogen; cytochrome P450 monooxygenase; detoxification

ABSTRAK

Dalam kajian sebelum ini, gen EgP450 yang mengekod 505 protein asid amino telah dipencilkan daripada kelapa sawit. Protein rekombinan EgP450 terikat kepada racun herba seperti phenylurea yang menyahtoksin bahan. Aflatoksin B1 (AFB1), mikotoksin yang dihasilkan oleh Aspergillus sp., adalah satu lagi toksik sebatian yang diketahui menyebabkan kesan toksik akut dan bertindak sebagai agen hepatokarsinogen. Kajian ini bertujuan untuk meneliti peranan enzim EgP450 dalam biopengaktifan mikotoksin sel stem mesenkim manusia (hMSCs). Analisis dok menunjukkan bahawa EgP450 terikat kepada kumpulan karsinogen, termasuk AFB1, n-(2-fluorenil) asetamid, n-n-butil-n-butan-4-ol-nitrosamin, n-nitrosodietilamin, n-nitrosodietilamin dan n-nitrosodimetilamin. Ujian in vivo ketoksikan aflatoksin ke atas hMSCs dan AFB1 mengaruh ekspresi Bmi_-1 yang merupakan salah satu penanda bagi pembangunan kanser. Kehadiran EgP450 pada 0.15 μg/mL boleh mengurangkan ekspresi Bmi-1 dalam sel aruhan AFB1. Selain itu, protein ini juga menunjukkan beberapa aktiviti antioksidan. Keputusan ini menunjukkan potensi besar EgP450 dalam proses penyahtoksikan.

Kata kunci: Karsinogen; penyahtoksikan; sitokrom P450 monooksigenase

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*Pengarang untuk surat-menyurat; email: pamornra@yahoo.com