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Antimetastatic activity of the photodynamic agent hypericin in the dark
Author(s) -
Blank Michael,
Lavie Gad,
Mandel Mathilda,
Hazan Sadick,
Orenstein Arie,
Meruelo Daniel,
Keisari Yona
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20285
Subject(s) - hypericin , in vivo , adenocarcinoma , photodynamic therapy , medicine , metastasis , cancer research , pathology , cancer , lung , biology , chemistry , pharmacology , microbiology and biotechnology , organic chemistry
Abstract 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. © 2004 Wiley‐Liss, Inc.