Effects of Pterostilbene on Activities and Protein Expression of Cytochrome P450 1A1 (CYP1A1) and Glutathione S-Transferase (GST) in Benzo[a]pyrene-Induced HT-29 Colorectal Cancer Cell Line

Abstract

Drug Metabolizing Enzyme (DME) has been a target of natural chemopreventive agents to inhibit, retard and reverse the process of carcinogenesis. Pterostilbene, an analog to resveratrol has been reported to possess various pharmacological benefits including chemoprevention. In our study, benzo[a]pyrene-induced HT-29 colorectal cell line was used as the DME model. The activity of phase I enzyme CYP1A as determined by the 7-ethoxyresorufin O-deethylation (EROD) assay was found to be inhibited significantly by pterostilbene at 50 µM, 75 µM and 100 µM (p ≤ 0.01, p ≤ 0.05, p ≤ 0.01 respectively) compared to the benzo[a]pyrene treated group. Meanwhile, pterostilbene induced glutathione-S-transferase (GST) activity significantly (p ≤ 0.01) at 50 µM as compared to the untreated. In addition, However, the protein expression of CYP1A1 and GST in pterostilbene treated group was not significantly affected compared to untreated. On the other hand, pterostilbene at 25 and 75 µM were able to increase the protein expression of transcription factor Nrf2 significantly (p ≤ 0.01). Results indicated that pterostilbene could reduce metabolic activation of procarcinogens and increase the detoxification process which can be potentially developed as chemopreventive agent. ABSTRAK Enzim Metabolisma Dadah (EMD) telah menjadi sasaran agen kemopencegahan semulajadi untuk menghalang, merencat dan membalikkan proses karsinogenesis. Pterostilbene, analog kepada resveratrol telah dilaporkan mempunyai pelbagai manfaat farmakologi termasuk kemopencegahan. Dalam kajian kami, sel pirena telah digunakan sebagai model EMD. Aktiviti enzim CYP1A fasa I ditentukan oleh asai 7-ethoxyresorufin O-deethylation (EROD) didapati merencat secara signifikan oleh pterostilbene pada kepekatan 50 μM, 75 μM dan 100 μM (p ≤ 0.01, p ≤ 0.05, p ≤ 0.01 masing-masing) berbanding dengan kumpulan yang dirawat dengan benzo [a]pirena. Selain itu, pterostilbene juga mengaruh aktiviti glutation-S-transferase (GST) secara signifikan (p ≤ 0.01) pada kepekatan 50 μM berbanding dengan kumpulan yang tidak dirawat. Di samping itu, pengekspresan protein CYP1A1 dan GST dalam kumpulan yang dirawat pterostilbene tidak memberi kesan secara signifikan berbanding kumpulan tidak dirawat. Sebaliknya, pterostilbene pada kepekatan 25 μM dan 75 μM dapat meningkatkan pengekspresan protein faktor transkripsi Nrf2 secara signifikan (p ≤ 0.01). Hasil kajian menunjukkan bahawa pterostilbene dapat mengurangkan pengaktifan metabolik prokarsinogen dan meningkatkan proses detoksifikasi yang berpotensi dapat dijadikan sebagai agen kemopencegahan.

Effect of styrene oxide and diethyl maleate on expression of cytochrome P450 family 1 and glutathione store in mouse liver

“…The lungs of rats exposed to styrene (750 ppm) for 4 weeks exhibited increases in malondialdehyde (MDA) levels, with associated decreases in catalase, superoxide dismutase, and GSH activities [18] and DEM has been shown to increase ROS levels in breast cancer [19]. The CYP1 inducer, benzo[a]pyrene induced EROD and glutathione-S-transferase activities in HT-29 colorectal cells [20]. The current study is the first that connects SO-and DEM-mediated up-regulation of Cyp1 expression with GSH depletion in mouse livers.…”

Chemopreventive Effects of Oral Pterostilbene in Multistage Carcinogenesis of Skin Squamous Cell Carcinoma Mouse Model Induced by DMBA/TPA

“…According to numerous epidemiological and pre-clinical studies, consuming natural food such as vegetables, fruits, herbs, and spices has been linked to lowering the risk of developing cancer [ 9 , 10 ]. Stilbene-based natural compounds, such as resveratrol and pterostilbene, are widely studied polyphenols with numerous pharmacological properties, including anti-inflammatory, antioxidant, anti-cancer, anti-diabetic, and others [ 11 , 12 , 13 , 14 , 15 ]. However, pterostilbene possesses better pharmacokinetic properties compared to resveratrol, with a longer half-life in the body and greater bioavailability [ 16 , 17 ].…”