Effects of Pterostilbene on O-deethylation and Glutathione Conjugation of Drug Metabolizing Enzyme Activities

Ghazali, Ahmad Rohi; Ki, Ong Sher; Hamid, Hasiah Ab; Room, Nurhusni Mohammad; Kamarulzam, Firdaus

doi:10.5567/pharmacologia.2012.456.461

Cited by 6 publications

(6 citation statements)

References 9 publications

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“…Our results were in agreement with Ciolino and Yeh, (1999) where they showed resveratrol had the ability to inhibit carcinogen activity by CYP1A1/1A2 enzymes in HepG2 cells competitively. As for pterostilbene, our results on pterostilbene treatment were in agreement with Ghazali et al, (2012) and Mikstacka et al, (2007). However, pterostilbene was not able to inhibit the protein expression of CYP1A1 significantly.…”

Section: Resultssupporting

confidence: 87%

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

Ghazali

Lee

Cheng

et al. 2018

JSKM

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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.

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Section: Resultssupporting

confidence: 87%

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

Ghazali

Lee

Cheng

et al. 2018

JSKM

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“…This study also found the same findings in which the significant increase in GST activity was reported at 12.5 µM and 25 µM but not 50 µM of pterostilbene treatment. Ghazali et al (2012) also showed a significant increase of GSH level at 25 µM and 50 µM that also reported in our study in which at 50 µM the GSH level also increase significantly compare to negative control. This suggests that at 25 µM pterostilbene treatment, GST activity increase thus there were a slight GSH level depleted, masking the induction effect by pterostilbene.…”

Section: Discussionsupporting

confidence: 89%

“…In addition our result was also demonstrated the similar significant effect with regard to the dose with the study by Ghazali et al (2012). In that study, they used the HepG2 cell line to investigate the effect of pterostilbene on GST activity and GSH level.…”

Section: Discussionsupporting

confidence: 86%

Potential Chemoprevention Activity of Pterostilbene by Enhancing the Detoxifying Enzymes in the HT-29 Cell Line

Harun¹,

Ghazali²

2012

Asian Pacific Journal of Cancer Prevention

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Detoxifying enzymes are present in most epithelial cells of the human gastrointestinal tract where they protect against xenobiotics which may cause cancer. Induction of examples such as glutathione S-transferase (GST) and its thiol conjugate, glutathione (GSH) as well as NAD(P)H: quinoneoxidoreductase (NQO1) facilitate the excretion of carcinogens and thus preventing colon carcinogenesis. Pterostilbene, an analogue of resveratrol, has demonstrated numerous pharmacological activities linked with chemoprevention. This study was conducted to investigate the potential of pterostilbene as a chemopreventive agent using the HT-29 colon cancer cell line to study the modulation of GST and NQO1 activities as well as the GSH level. Initially, our group, established the optimum dose of 24 hours pterostilbene treatment using MTT assays. Then, effects of pterostilbene (0-50 µM) on GST and NQO1 activity and GSH levels were determined using GST, NQO1 and Ellman assays, respectively. MTT assay of pterostilbene (0-100 µM) showed no cytotoxicity toward the HT-29 cell line. Treatment increased GST activity in the cell line significantly (p<0.05) at 12.5 and 25.0 μM. In addition, treatment at 50 μM increased the GSH level significantly (p<0.05). Pterostilbene also enhanced NQO1 activity significantly (p<0.05) at 12.5 µM and 50 µM. Hence, pterostilbene is a potential chemopreventive agent capable of modulation of detoxifiying enzyme levels in HT-29 cells.

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“…Phytoalexin has antimicrobial property which serves as part of the plant defense system against pathogen and herbivore (Chong et al, 2009). Additionally, pterostilbene has demonstrated potential antioxidant (Rimando et al, 2002), anti-fungal (Li et al, 2014), anti-glycemic (Grover et al, 2005), anti-mutagenic and anticarcinogenic properties (Chio et al, 2011;Ghazali et al, 2012;McCormack and McFadden, 2012) which indicated the potential of pterostilbene in the prevention of certain illnesses and infectious diseases.…”

Section: Introductionmentioning

confidence: 99%

Pterostilbene Enhanced Anti-Methicillin Resistant <i>Staphylococcus aureus</i> (MRSA) Activity of Oxacillin

Ishak¹,

Ghazali²,

Zin³

et al. 2016

American Journal of Infectious Diseases

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Methicillin-resistant Staphylococcus aureus (MRSA) is a deadly pathogen that initially was limited to hospital and healthcare facilities but has gradually became a growing problem in healthy children and adults. Pterostilbene belongs to the phenylpropanoid phytoalexin which is involved in plant response to various pathogen and herbivores attack. The aim of this study is to evaluate the anti-MRSA action of pterostilbene in combination with selected antibiotics; vancomycin, linezolid and oxacillin against ATCC 43300 and ATCC 33591. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and fractional inhibitory concentration (FIC) index values were determined. Microbroth dilution technique and microdilution checkerboard (MDC) assay were employed. The MIC and MBC of pterostilbene against ATCC 33591 was 31.25 and 62.50 µg mL −1 , respectively. While for ATCC 43300, the MBC value was also twice (62.50 µg mL −1 ) its MIC value of 31.25 µg mL −1 . This indicated that pterostilbene was bacteriostatic against both MRSA strains. Our MIC/MBC study also showed that linezolid exhibited bacteriostatic action but, oxacillin and vancomycin were bactericidal. MDC study showed that pterostilbene-oxacillin combination exhibited lowest FIC value (0.56) against both MRSA strains which indicated partial synergistic interaction. On the other hand, pterostilbene was additive (FIC 1.00) in combination with vancomycin whereas pterostilbene-linezolid combination displayed indifference effect with FIC of 1.25 against both MRSA strains. Pterostilbene in combination with oxacillin partially enhanced anti-MRSA activity with twofold reduction in MIC of oxacillin by acting at different site at the bacterial cell wall from that of oxacillin but more specific to the site of action of vancomycin.

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Effects of Pterostilbene on O-deethylation and Glutathione Conjugation of Drug Metabolizing Enzyme Activities

Cited by 6 publications

References 9 publications

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

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

Potential Chemoprevention Activity of Pterostilbene by Enhancing the Detoxifying Enzymes in the HT-29 Cell Line

Pterostilbene Enhanced Anti-Methicillin Resistant <i>Staphylococcus aureus</i> (MRSA) Activity of Oxacillin

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