Auraptene Attenuates Malignant Properties of Esophageal Stem-Like Cancer Cells

• Published in: Technology in cancer research & treatment 2017-08, Vol.16 (4), p.519-527
• Main Authors: Saboor-Maleki, Saffiyeh, Rassouli, Fatemeh B., Matin, Maryam M., Iranshahi, Mehrdad
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Antineoplastic Agents - pharmacology; Antineoplastic drugs; Antitumor agents; Apoptosis; Apoptosis - drug effects; Bmi protein; Cancer therapies; CD44 antigen; Cell differentiation; Cell Line, Tumor; Chemoresistance; Chemotherapy; Cisplatin; Cisplatin - pharmacology; Coumarin; Coumarins - pharmacology; Cyclin-dependent kinase inhibitor p21; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Drug Screening Assays, Antitumor; Drug Synergism; Esophageal cancer; Esophageal carcinoma; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - pathology; Esophagus; Flow cytometry; Fluorouracil - pharmacology; Gene Expression - drug effects; Humans; Hyaluronan Receptors - genetics; Hyaluronan Receptors - metabolism; Inhibitory Concentration 50; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - physiology; p53 Protein; Paclitaxel; Paclitaxel - pharmacology; Polycomb Repressive Complex 1 - genetics; Polycomb Repressive Complex 1 - metabolism; Polymerase chain reaction; Squamous cell carcinoma; Toxicity; Tumor Biology; Tumor suppressor genes; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism
• ISSN: 1533-0346; 1533-0338
• DOI: 10.1177/1533034616650119

The high incidence of esophageal squamous cell carcinoma has been reported in selected ethnic populations including North of Iran. Low survival rate of esophageal carcinoma is partially due to the presence of stem-like cancer cells with chemotherapy resistance. In the current study, we aimed to determine the effects of auraptene, an interesting dietary coumarin with various biological activities, on malignant properties of stem-like esophageal squamous cell carcinoma, in terms of sensitivity to anticancer drugs and expression of specific markers. To do so, the half maximal inhibitory concentration values of auraptene, cisplatin, paclitaxel, and 5-fluorouracil were determined on esophageal carcinoma cells (KYSE30 cell line). After administrating combinatorial treatments, including nontoxic concentrations of auraptene + cisplatin, paclitaxel, or 5-fluorouracil, sensitivity of cells to chemical drugs and also induced apoptosis were assessed. In addition, quantitative real-time polymerase chain reaction was used to study changes in the expression of tumor suppressor proteins 53 and 21 (P53 and P21), cluster of differentiation 44 (CD44), and B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) upon treatments. Results of thiazolyl blue assay revealed that auraptene significantly (P < .05) increased toxicity of cisplatin, paclitaxel, and 5-fluorouracil in KYSE30 cells, specifically 72 hours after treatment. Conducting an apoptosis assay using flow cytometry also confirmed the synergic effects of auraptene. Results of quantitative real-time polymerase chain reaction revealed significant (P < .05) upregulation of P53 and P21 upon combinatorial treatments and also downregulation of CD44 and BMI-1 after auraptene administration. Current study provided evidence, for the first time, that auraptene attenuates the properties of esophageal stem-like cancer cells through enhancing sensitivity to chemical agents and reducing the expression of CD44 and BMI-1 markers.