Degradation of HER2 receptor through hypericin-mediated photodynamic therapy.
Current treatment of breast cancer is often affected by resistance to therapeutics, for which the human epidermal growth factor receptor 2 (HER2) may be responsible. Here, we report for the first time the use of hypericin-mediated photodynamic therapy (HY-PDT) in combination with a selective HER2 inhibitor (AG 825) on SKBR-3, a HER2 overexpressing human breast adenocarcinoma cell line. The results demonstrate that HY-PDT is able to degrade HER2 with an impact on its signaling cascade. Combination with AG 825 resulted in increased apoptosis induction, total degradation of HER2 and inhibition of colony formation. Downregulation of HSP90, Mcl-1, Bcl-xL and upregulation of Bax was also observed. This knowledge provides the basis for the possible application of HY-PDT in preclinical and clinical models of breast cancer treatment.
Koval
Ján
J
Faculty of Sciences, Institute of Biology and Ecology, P. J. Safárik University in Kosice, Kosice, Slovakia.
Mikes
Jaromír
J
Jendzelovský
Rastislav
R
Kello
Martin
M
Solár
Peter
P
Fedorocko
Peter
P
D000873:Anthracenes; D017209:Apoptosis / Q000187:drug effects; D052160:Benzothiazoles / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D010569:Perylene / Q000031:analogs & derivatives; D010778:Photochemotherapy / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020032:Tyrphostins / Q000494:pharmacology
D000873:Anthracenes; D052160:Benzothiazoles; D010569:Perylene; D018719:Erb-b2 Receptor Tyrosine Kinases; D020032:Tyrphostins; C098214:tyrphostin AG825; C004965:hypericin; C508053:ERBB2 protein, human