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

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Nowruz NajafzadehMojtaba Amani

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 24h. 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 (1μM, 6days) followed by 5-FU and ...Continue Reading

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Citations

Aug 5, 2017·Future Oncology·Raheleh RoudiZahra Madjd
Nov 13, 2018·Journal of Cellular Physiology·Haleh MokabberMohammad Mohammadzadeh Vardin
Dec 7, 2019·Fundamental & Clinical Pharmacology·Cheng WangKun Qian
Oct 18, 2018·Journal of Experimental & Clinical Cancer Research : CR·Yang WangYuan Zhang
Jul 29, 2020·Frontiers in Pharmacology·Junxia WuChangchun Cao
Nov 13, 2020·Clinical and Experimental Gastroenterology·Khadijeh Kalan FarmanfarmaHamid Salehiniya
Jul 3, 2021·International Journal of Molecular Sciences·Yeon Ju KimYun-Hoon Choung

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