Bio-distribution and subcellular localization of Hypericin and its role in PDT induced apoptosis in cancer cells

  • Authors:
    • Seyed Mohamed Ali
    • Malini Olivo
  • View Affiliations

  • Published online on: September 1, 2002     https://doi.org/10.3892/ijo.21.3.531
  • Pages: 531-540
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Abstract

The development of new-generation photosensitizers to improve photodynamic therapy (PDT) and photodynamic diagnosis (PDD) is an area of extensive research. One such compound that has been studied in our group is Hypericin (HY). To study the mechanism of action we have investigated uptake, intracellular localization, cell phototoxicity and morphological changes especially to ultrastructures following photodynamic treatment in poorly (CNE2) and moderately (TW0-1) differentiated human nasopharyngeal carcinoma (NPC) cells and also other tumor cells such as colon (CCL-220.1) and bladder (SD) cells in vitro. Following irradiation, phototoxicity was determined by crystal fast violet assay and apoptosis was assessed using annexin-V assay. Using spectrofluorimetry and confocal laser scanning microscopy (CLSM) we have determined cellular fluorescence localization and uptake of HY. Co-labeling with HY and fluorescent dyes specific for cell organelles revealed an intracellular localization of HY predominantly in mitochondria and lysosomes. Since many photosensitizing agents in current clinical use have mitochondrial targets, HY may be a valuable addition to current protocols. In addition, our results also indicate that leakage of lysosomal protease into cytosolic compartment might be involved in the induction of apoptosis. Electron microscopy revealed damage to plasma membrane with high drug dose (>5 μM); indicating a mechanism related to necrosis, whereas sub-lethal lower doses (<2.5 μM) resulted in induction of apoptosis indicated by typical ultrastructural signs of apoptosis. Our results based on mitochondrial and lysosomal localization support the idea that PDT can contribute to elimination of malignant cells by the induction of apoptosis, and can be of physiological significance.

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September 2002
Volume 21 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Ali SM and Ali SM: Bio-distribution and subcellular localization of Hypericin and its role in PDT induced apoptosis in cancer cells. Int J Oncol 21: 531-540, 2002
APA
Ali, S.M., & Ali, S.M. (2002). Bio-distribution and subcellular localization of Hypericin and its role in PDT induced apoptosis in cancer cells. International Journal of Oncology, 21, 531-540. https://doi.org/10.3892/ijo.21.3.531
MLA
Ali, S. M., Olivo, M."Bio-distribution and subcellular localization of Hypericin and its role in PDT induced apoptosis in cancer cells". International Journal of Oncology 21.3 (2002): 531-540.
Chicago
Ali, S. M., Olivo, M."Bio-distribution and subcellular localization of Hypericin and its role in PDT induced apoptosis in cancer cells". International Journal of Oncology 21, no. 3 (2002): 531-540. https://doi.org/10.3892/ijo.21.3.531