Effects of photoactivated 5-aminolevulinic acid hexyl ester on MDR1 over-expressing human uterine sarcoma cells.
The role of multi-drug resistance (MDR1) and its product, P-glycoprotein (P-gp) on 5-aminolevulinic acid hexyl ester (Hexyl-ALA) mediated phototoxicity was determined with human uterine sarcoma cells, MES-SA control and MDR1 expressing MES-SA-Dx5. MDR1 expression reduced intracellular levels of the Hexyl-ALA metabolite, protoporphyrin IX (PpIX) to a limited degree and could be reversed with a P-gp inhibitor, verapamil. P-gp expression also reduced Hexyl-ALA photosensitivity. More importantly, photoactivated Hexyl-ALA reduced at the mRNA and protein levels without altering housekeeping GAPDH mRNA. These findings suggest that Hexyl-ALA could be used to selectively reduce P-gp expression in overcoming resistance to chemotherapy agents such as doxorubicin and paclitaxel.
Chu
Ellie S M
ES
Medical Laboratory Science Section, Department of Health Technology and Informatics, Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China.
Yow
Christine M N
CM
Shi
Mark
M
Ho
Rodney J Y
RJ
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D010778:Photochemotherapy; D012333:RNA, Messenger / Q000032:analysis; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014700:Verapamil / Q000494:pharmacology
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger; D000622:Aminolevulinic Acid; D014700:Verapamil; C419924:5-aminolevulinic acid hexyl ester