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

Seyed Mohamed Ali, Malini Olivo

Research output: Contribution to journalArticle

89 Citations (Scopus)

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 microM); indicating a mechanism related to necrosis, whereas sub-lethal lower doses (<2.5 microM) 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.

Original languageEnglish
Pages (from-to)531-540
Number of pages10
JournalInternational Journal of Oncology
Volume21
Issue number3
Publication statusPublished - Sep 2002
Externally publishedYes

Fingerprint

Photochemotherapy
Apoptosis
Phototoxic Dermatitis
Neoplasms
Photosensitizing Agents
Gentian Violet
Annexin A5
Lysosomes
Fluorescent Dyes
Confocal Microscopy
Organelles
hypericin
Electron Microscopy
Mitochondria
Colon
Urinary Bladder
Peptide Hydrolases
Necrosis
Fluorescence
Cell Membrane

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bio-distribution and subcellular localization of Hypericin and its role in PDT induced apoptosis in cancer cells. / Ali, Seyed Mohamed; Olivo, Malini.

In: International Journal of Oncology, Vol. 21, No. 3, 09.2002, p. 531-540.

Research output: Contribution to journalArticle

@article{5ee3676427894462bb6a7daacc926638,
title = "Bio-distribution and subcellular localization of Hypericin and its role in PDT induced apoptosis in cancer cells.",
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 microM); indicating a mechanism related to necrosis, whereas sub-lethal lower doses (<2.5 microM) 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.",
author = "Ali, {Seyed Mohamed} and Malini Olivo",
year = "2002",
month = "9",
language = "English",
volume = "21",
pages = "531--540",
journal = "International Journal of Oncology",
issn = "1019-6439",
publisher = "Spandidos Publications",
number = "3",

}

TY - JOUR

T1 - Bio-distribution and subcellular localization of Hypericin and its role in PDT induced apoptosis in cancer cells.

AU - Ali, Seyed Mohamed

AU - Olivo, Malini

PY - 2002/9

Y1 - 2002/9

N2 - 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 microM); indicating a mechanism related to necrosis, whereas sub-lethal lower doses (<2.5 microM) 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.

AB - 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 microM); indicating a mechanism related to necrosis, whereas sub-lethal lower doses (<2.5 microM) 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.

UR - http://www.scopus.com/inward/record.url?scp=0036730708&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036730708&partnerID=8YFLogxK

M3 - Article

C2 - 12168096

AN - SCOPUS:0036730708

VL - 21

SP - 531

EP - 540

JO - International Journal of Oncology

JF - International Journal of Oncology

SN - 1019-6439

IS - 3

ER -