Antimetastatic activity of the photodynamic agent hypericin in the dark.
A unique property of the photodynamic signal transduction inhibitor hypericin (HY) is high functionality in the dark, which has been shown to result in portfolio of anticancer activities both in vitro and in vivo. Here we show that treatment with HY significantly reduces growth rate of metastases in 2 murine models: breast adenocarcinoma (DA3) and squamous cell carcinoma (SQ2). Focus on metastases was achieved by resection of primary tumors at stages in which micrometastases exist in lungs. Long-term animal survival in DA3 tumor-excised groups increased from 15.6% in controls to 34.5% following supplementary treatment with HY. In mice bearing SQ2 tumor metastases, therapy with HY increased animal survival from 17.7% in controls to 46.1%. Using Laser-induced fluorescence and multipixel spectral image analyses, we demonstrate that HY has a high tendency to accumulate in primary and metastatic tumors; HY content in lungs bearing metastases was approximately 2-fold higher than in the lungs of healthy animals. The tendency of HY to preferentially concentrate in lung metastases, combined with its potent antiproliferative activities, may render HY as a useful supplementary modality in the treatment of metastatic cancer irrespective of photoactivation.
Blank
Michael
M
Department of Human Microbiology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Lavie
Gad
G
Mandel
Mathilda
M
Hazan
Sadick
S
Orenstein
Arie
A
Meruelo
Daniel
D
Keisari
Yona
Y
D000818:Animals; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology* / Q000662:veterinary; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000662:veterinary; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008027:Light; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000662:veterinary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010569:Perylene / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D015398:Signal Transduction; D016019:Survival Analysis; D014018:Tissue Distribution
D000873:Anthracenes; D000970:Antineoplastic Agents; D010569:Perylene; C004965:hypericin