Cytochrome P450 and Glutathione Transferase Expression in Squamous Cell Cancer

Ali, Shadan; El-Rayes, B. F.; Heilbrun, Lance K.; Sarkar, Fazlul H.; Ensley, John F.; Kucuk, Omar; Philip, Philip A.

doi:10.1158/1078-0432.ccr-04-0145

Cited by 15 publications

(13 citation statements)

References 30 publications

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“…The relationship between GSTP1 expression and carcinogenesis has been differently reported in OSCC . The inconsistent results might be caused by large individual variability in the expression of GSTP1 enzymes in different patients . In our study, we confirmed the decreased GSTP1 expression in OSCC, not only in OSCC lines, but also in patients with OSCC and a correlation between the GSTP1 expression and differentiation of the tumor was also found.…”

Section: Discussionsupporting

confidence: 81%

Decreased expression of glutathione S‐transferase pi correlates with poorly differentiated grade in patients with oral squamous cell carcinoma

Liu

et al. 2014

J Oral Pathology Medicine

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Section: Discussionsupporting

confidence: 81%

Decreased expression of glutathione S‐transferase pi correlates with poorly differentiated grade in patients with oral squamous cell carcinoma

Liu

et al. 2014

J Oral Pathology Medicine

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“…It achieves so by undergoing metabolic activation by cytochrome P450 2E1 and generates electrophilic substances that form DNA adducts . Therefore, in chemically induced carcinogenesis, carcinogen activating enzyme expression is a critical component as it holds a very high proliferative potential of pushing usual cells to a cancerous phenotype . In the present study, the raised the activities of the cytochrome P450 family enzymes in colonic mucosa DMH treated rats was observed.…”

Section: Discussionsupporting

confidence: 50%

Chemopreventive efficacy zingerone (4‐[4‐hydroxy‐3‐methylphenyl] butan‐2‐one) in experimental colon carcinogenesis in Wistar rats

Ganaie

Saeedan

Madhkali

et al. 2019

Environmental Toxicology

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Colorectal cancer is one of the most common cancers worldwide. Development of naturally occurring inexpensive and safe alternatives can be effective in suppressing colon related proliferations. Zingerone (4-[4-hydroxy-3-methylphenyl] butan-2-one), a polyphenolic alkanone of ginger, has massive pharmacological properties and thus can be used as promising candidate against various ailments. In the current study, we aimed at demonstrating the protective effect of zingerone against experimental colon carcinogenesis and elucidating its possible mechanism by studying inflammatory and Nrf-2 signaling cascade. Four groups of animals (I-IV) were made with six animals each. Group I (control) was given normal saline orally. Group II was given 1,2-dimethylhydrazine (DMH) at the dose rate of 20 mg/kg body weight. Group III and IV were treated with DMH at the dose rate of 20 mg/kg body weight and also received oral treatment of zingerone at a dose rate of 50 and 100 mg/kg body weight, respectively, for first 5 weeks and animals were euthanized after 16 weeks. Our results reveal that DMH treated rats exhibited elevated ROS and MDA levels, increased activity of cytochrome P450 2E1 and serum marker enzyme carcinoembreyonic antigen (CEA), increased no of aberrant crypts of foci (ACF), and elevated expression of inflammatory and proliferative proteins. Nrf-2 was downregulated by DMH treatment. Treatment with zingerone to DMH treated rats, resulted in alterations in the activity of the cytochrome P450 2E1 and CEA. In addition, immunostaining of NF-kB-p65, COX-2, iNOS, and PCNA, Ki-67 was suppressed by zingerone. Furthermore, zingerone administration also attenuated the level of IL-6 and TNF-α and it also helps in preserving mucous layer.Thus, zingerone could be considered as a good chemopreventive agent in experimental model of colon carcinogenesis. Further studies are required to study other pathways involved in colon carcinogenesis and their modulation buy zingerone. K E Y W O R D S chemoprevention, colon cancer, hyperproliferation, inflammation, natural product, zingerone 1 | INTRODUCTION Cancer is the leading cause of death in developed and developing nations. In under developed countries, it is the second most cause of death. 1 Colon cancer is the third most frequent malignancy and fourth most common cause of mortality in both the genders throughout the world. 2 It arises due to varied alterations (genetic as well as epigenetic) in the colonic epithelium. 3 Epidemiological studies have shown that there exists an interaction between diet and the prevalence of colorectal cancer which can be promoted by a diet rich in fat and meat. Experimental colon carcinogenesis is induced by 1,2-dimethylhydrazine (DMH) in rodents mostly in distal part of the colon. DMH induced pathological and molecular events are similar to those observed in human colon cancer. 4,5

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“…A higher frequency of G to T transversion has been documented in animals exposed to PAH carcinogens (37). The enhanced activities of phase I and II enzymes as well as increased expression of 8-OH-dG seen in HBP tumours in the present study corroborate overexpression of these enzymes and oxidative DNA damage reported in cell lines and malignant tumours (26,38,39).…”

Section: Biochemical Findingssupporting

confidence: 88%

Pretreatment With Black Tea Polyphenols Modulates Xenobiotic-Metabolizing Enzymes in an Experimental Oral Carcinogenesis Model

et al. 2008

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Objective-To evaluate the chemopreventive potential of the black tea polyphenols Polyphenon-B and BTF-35 during the preinitiation phase of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis.Design-Hamsters were divided into 6 groups. Groups 2 and 3 animals received diet containing Polyphenon-B and BTF-35 respectively, four weeks before carcinogen administration when they were 6 weeks of age and continued until the final exposure to carcinogen. At 10 weeks of age, animals in groups 1, 2 and 3 were painted with 0.5% DMBA 3 times a week for 14 weeks. Groups 4 and 5 animals were given Polyphenon-B and BTF-35 alone respectively as in groups 2 and 3. Animals in group 6 served as control. All the animals were sacrificed after an experimental period of 18 weeks. Phase I and phase II xenobiotic-metabolizing enzymes and 8-hydroxy deoxyguanosine (8-OH dG) in the buccal pouch and liver were used as biomarkers of chemoprevention.Results-Hamsters painted with DMBA showed increased expression of 8-OH-dG and enhanced activities of phase I (CYP450; total as well as CYP1A1, 1A2 and 2B isoforms and cytochrome b 5 ) and phase II (GST and quinone reductase) xenobiotic-metabolizing enzymes with increased immunohistochemical expression of CYP1A1, and CYP1B1 isoforms in the buccal pouch. This was accompanied by increased phase I and decreased phase II enzyme activities in the liver. Administration of Polyphenon-B and BTF-35 significantly decreased tumour incidence, oxidative DNA damage, phase I enzyme activities as well as expression of CYP1A1 and CYP1B1 isoforms, while enhancing phase II enzyme activities in the buccal pouch and liver.Conclusion-Our results provide a mechanistic basis for the chemopreventive potential of black tea polyphenols. Furthermore, the greater efficacy of BTF-35 in chemoprevention of HBP carcinomas via inhibition of oxidative DNA damage and modulation of xenobiotic-metabolizing enzymes may have a major impact in human oral cancer prevention.

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Cytochrome P450 and Glutathione Transferase Expression in Squamous Cell Cancer

Cited by 15 publications

References 30 publications

Decreased expression of glutathione S‐transferase pi correlates with poorly differentiated grade in patients with oral squamous cell carcinoma

Decreased expression of glutathione S‐transferase pi correlates with poorly differentiated grade in patients with oral squamous cell carcinoma

Chemopreventive efficacy zingerone (4‐[4‐hydroxy‐3‐methylphenyl] butan‐2‐one) in experimental colon carcinogenesis in Wistar rats

Pretreatment With Black Tea Polyphenols Modulates Xenobiotic-Metabolizing Enzymes in an Experimental Oral Carcinogenesis Model

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