Evaluation of Novel 3-Hydroxyflavone Analogues as HDAC Inhibitors against Colorectal Cancer
المؤلفون المشاركون
Reddy, Neetinkumar D.
Biswas, Subhankar
Rao, C. Mallikarjuna
Jayashree, B. S.
المصدر
Advances in Pharmacological and Pharmaceutical Sciences
العدد
المجلد 2018، العدد 2018 (31 ديسمبر/كانون الأول 2018)، ص ص. 1-14، 14ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2018-12-27
دولة النشر
مصر
عدد الصفحات
14
التخصصات الرئيسية
الملخص EN
Alteration of epigenetic enzymes is associated with the pathophysiology of colon cancer with an overexpression of histone deacetylase 8 (HDAC8) enzyme in this tissue.
Numerous reports suggest that targeting HDAC8 is a viable strategy for developing new anticancer drugs.
Flavonols provide a rich source of molecules that are effective against cancer; however, their clinical use is limited.
The present study investigated the potential of quercetin and synthetic 3-hydroxyflavone analogues to inhibit HDAC8 enzyme and evaluated their anticancer property.
Synthesis of the analogues was carried out, and cytotoxicity was determined using MTT assay.
Nonspecific and specific HDAC enzyme inhibition assays were performed followed by the expression studies of target proteins.
Induction of apoptosis was studied through annexin V and caspase 3/7 activation assay.
Furthermore, the analogues were assessed against in vivo colorectal cancer.
Among the synthesized analogues, QMJ-2 and QMJ-5 were cytotoxic against HCT116 cells with an IC50 value of 68 ± 2.3 and 27.4 ± 1.8 µM, respectively.
They inhibited HDAC enzyme in HCT116 cells at an IC50 value of 181.7 ± 22.04 and 70.2 ± 4.3 µM, respectively, and inhibited human HDAC8 and 1 enzyme at an IC50 value of <50 µM with QMJ-5 having greater specificity towards HDAC8.
A reduction in the expression of HDAC8 and an increase in acetyl H3K9 expression were observed with the synthesized analogues.
Both QMJ-2 and QMJ-5 treatment induced apoptosis through the activation of caspase 3/7 evident from 55.70% and 83.55% apoptotic cells, respectively.
In vivo studies revealed a significant decrease in colon weight to length ratio in QMJ-2 and QMJ-5 treatment groups compared to DMH control.
Furthermore, a reduction in aberrant crypt foci formation was observed in the treatment groups.
The present study demonstrated the potential of novel 3-hydroxyflavone analogues as HDAC8 inhibitors with anticancer property against colorectal cancer.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Biswas, Subhankar& Reddy, Neetinkumar D.& Jayashree, B. S.& Rao, C. Mallikarjuna. 2018. Evaluation of Novel 3-Hydroxyflavone Analogues as HDAC Inhibitors against Colorectal Cancer. Advances in Pharmacological and Pharmaceutical Sciences،Vol. 2018, no. 2018, pp.1-14.
https://search.emarefa.net/detail/BIM-1122774
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Biswas, Subhankar…[et al.]. Evaluation of Novel 3-Hydroxyflavone Analogues as HDAC Inhibitors against Colorectal Cancer. Advances in Pharmacological and Pharmaceutical Sciences No. 2018 (2018), pp.1-14.
https://search.emarefa.net/detail/BIM-1122774
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Biswas, Subhankar& Reddy, Neetinkumar D.& Jayashree, B. S.& Rao, C. Mallikarjuna. Evaluation of Novel 3-Hydroxyflavone Analogues as HDAC Inhibitors against Colorectal Cancer. Advances in Pharmacological and Pharmaceutical Sciences. 2018. Vol. 2018, no. 2018, pp.1-14.
https://search.emarefa.net/detail/BIM-1122774
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1122774
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر