Psoralen reverses docetaxel-induced multidrug resistance in A549/D16 human lung cancer cells lines.
Chemotherapy is the recommended treatment for advanced-stage cancers. However, the emergence of multidrug resistance (MDR), the ability of cancer cells to become simultaneously resistant to different drugs, limits the efficacy of chemotherapy. Previous studies have shown that herbal medicine or natural food may be feasible for various cancers as potent chemopreventive drug. This study aims to explore the capablility of reversing the multidrug resistance of docetaxel (DOC)-resistant A549 cells (A549/D16) of psoralen and the underlying mechanisms. In this study, results showed that the cell viability of A549/D16 subline is decreased when treated with psoralen plus DOC, while psoralen has no effect on the cell proliferation on A549 and A549/D16 cells. Furthermore, mRNA and proteins levels of ABCB1 were decreased in the presence of psoralen, while decreased ABCB1 activity was also revealed by flow cytometry. Based on these results, we believe that psoralen may be feasible for reversing the multidrug resistance by inhibiting ABCB1 gene and protein expression. Such inhibition will lead to a decrease in ABCB1 activity and anti-cancer drug efflux, which eventually result in drug resistance reversal and therefore, sensitizing drug-resistant cells to death in combination with chemotherapeutic drugs.
Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan; School of Optometry, Chung Shan Medical University, Taichung 40201, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
Ming-Ju
MJ
Hsieh
Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan.
Mu-Kuan
MK
Chen
Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Laboratory, Chang-Hua Hospital, Department of Health, Changhua 513, Taiwan.
Ya-Yen
YY
Yu
Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung 40201, Taiwan. Electronic address: gtsheu@csmu.edu.tw.
Gwo-Tarng
GT
Sheu
School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan. Electronic address: hlchiou@csmu.edu.tw.
Hui-Ling
HL
Chiou
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005363:Ficusin / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000009:adverse effects*
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D043823:Taxoids; D000077143:Docetaxel; D005363:Ficusin
ABCB1; Docetaxel; Lung cancer; Multidrug resistance; P-Glycoprotein; Psoralen