title

دوز پایین رتینوئیک تمام ترانس اثرات سمیت سلولی سیس پلاتین و 5 فلوئورواوراسیل را در سلولهای بنیادی CD44 مثبت افزایش می دهد

نجف زاده, نوروز and مأذنی, محمد and عباسی, اسدالله and فراستی, فریس and امانی, مجتبی (1394) دوز پایین رتینوئیک تمام ترانس اثرات سمیت سلولی سیس پلاتین و 5 فلوئورواوراسیل را در سلولهای بنیادی CD44 مثبت افزایش می دهد. Biomedicine & Pharmacotherapy ــ 74 . pp. 243-251. شاپا 0753-3322

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Title

Low-dose all-trans retinoic acid enhances cytotoxicity of cisplatin and 5-fluorouracil on CD44+ cancer stem cells

English Abstract

Cis-diamminedichloridoplatinum(II)(CDDP)-based combination chemotherapy is frequently used in gastrointestinal cancer. The synergistic mechanism of all-trans retinoic acid (ATRA), cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination remains unclear. Despite their potent antitumor properties, resistance to CDDP and 5-FU develops frequently in tumors. To clarify this mechanism, we determined the sensitivity to each drug and their combination in two gastrointestinal cancer stem cells (CSCs) subpopulation. Here, we report the identification and separation of CD44+ cells from human gastric carcinoma (AGS) and human esophageal squamous cell carcinoma (KYSE-30) cancer cell lines by magnetic activated cell sorting (MACS). We allowed the CD44± cells to grow 6 days at a subtoxic concentration of ATRA and then treated with different concentration of CDDP and 5-FU for 24 h. The cytotoxicity was examined by cell proliferation MTT assay. Additionally, AO/EB staining was used for detection of apoptotic cells. In order to determine whether the growth inhibition was also associated with changes in cell cycle distribution, cell cycle analysis was performed using flow cytometry. Low concentration of ATRA (1 μM, 6days) followed by 5-FU and CDDP was found to be more effective than either drugs alone, thus resulting in synergistic cytotoxicity in Kyse-30 and AGSCD44± cells. Furthermore, there was an indication that the combination of ATRA with 5FU and CDDP caused an increase in cell cycle arrest in G2/M and G0/G1. We conclude that low concentration of ATRA enhances the cytotoxicity of CDDP and 5FU by facilitating apoptosis and cell cycle arrest in gastrointestinal CSCs and provide a rational basis for the design of novel, well-tolerated CDDP- and 5FU-based chemotherapy in human gastrointestinal carcinoma.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :نوروز نجف زاده
نویسنده :محمد مأذنی
نویسنده :اسدالله عباسی
نویسنده :فریس فراستی
نویسنده مسئول :مجتبی امانی
Additional Information:Impact Factor(2014) 2.023 Indexed in: ISI, Pubmed\index Medicus\ Medline, Scoups, ScienceDirect, Embase
کلیدواژه ها (انگلیسی):All-trans retinoic acid; Cisplatin; 5-Fluorouracil; Cancer stem cells; CD44
Subjects:QU Biochemistry
WI Digestive System
Divisions:Faculty of Medicine > Department of Basic Sciences > Department of Biophysics
Faculty of Medicine > Department of Basic Sciences > Department of Biochemistry
Faculty of Medicine > Department of Basic Sciences > Department of Anatomy
ID Code:6897
Deposited By: Dr Nowruz Najafzadeh
Deposited On:15 Jun 1394 20:30
Last Modified:23 Jun 1394 08:22

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