The Anticancer Activity Of A Novel 8-hydroxyquinoline Derivatives Against 5-fluorouracil Resistant Colorectal Cancer Cells

الموضوعات

علوم بحتة وطبيعية

الملخص

Cancer is a global health crisis for which 20 million new cases were diagnosed in 2022 alone, with 9.3 million cancer-related deaths. Nearly 900,000 deaths were due to colorectal cancer (CRC), which is the third leading cause of cancer related mortality. In the United Arab Emirates, 550 new cases of CRC were reported in 2022. A major clinical challenge with CRC treatment is the development of resistance to 5-fluorouracil (5FU)-based chemotherapy regimens, which are the standard treatment for CRC. In the present study, the anticancer activity of two novel 8-hydroxyquinoline (8-HQ) derivatives AS45 and AS47 was examined against 5FU-sensitive (HCT116) and 5FU-resistant (5FU-R-HCT116) human CRC cell lines. Both 8-HQ derivatives were found to inhibit the viability as well as the colony formation ability of HCT116 and 5FU-R-HCT116 cells. Based on the results of both viability and colony formation assay, AS47 was selected as the candidate 8HQ derivative with potent activity. Further analysis revealed AS47 induced senescence in HCT116 cells, as confirmed by positive staining for senescence-associated β-galactosidase and downregulation of cell cycle associated protein cyclin D1 and the upregulation of p21 and p27. In contrast, AS47 induced autophagy in 5FU-R-HCT116 cells, which was confirmed by accumulation of LC3B-II on Western blotting. Lastly, AS47 inhibit the migratory capacity of both cell lines, demonstrated by its ability to prevent wound closure in wound healing assay. Our collective data suggest that the novel 8-HQ derivative AS47 is a promising anticancer agent for both 5FU-sensitive and 5FU-resistant CRC and should be studied further.

روابط وملفات

التعريف والنوع

رقم الوثيقة

09137627-fc45-42e0-bde8-5c3c18393ecb

رقم العقد

0

نوع الوسائط

Crawler

نوع المحتوى

الرسائل العلمية

صيغة المصدر

رسائل ماجيستير

نوع الملف

pdf text

أسماء الملفات

840792_1.pdf

بيانات النشر

ترجمة العنوان

النشاط المضاد للسرطان لمشتقات 8-الهيدروكسي كينولين الجديدة ضد خلايا سرطان القولون والمستقيم المقاومة لل5 فلورويوراسيل

ألقاب المؤلفين

[{"name_ar":"Mazoun Talal Al Azzani","title_ar":"اعداد","title_en":"Preparation"},{"name_ar":"Prof Rabah Iratni","title_ar":"اشراف","title_en":"Supervision"}]

اللغة

English

المصدر والدورية

اسم المصدر

The Anticancer Activity Of A Novel 8-hydroxyquinoline Derivatives Against 5-fluorouracil Resistant Colorectal Cancer Cells

المحتوى والصفحات

عدد الصفحات

0

إشراف وإعداد

الإشراف

Prof Rabah Iratni

الإعداد

Mazoun Talal Al Azzani

الاقتباسات الببليوغرافية