Zinc-pheophorbide a-highly efficient low-cost photosensitizer against human adenocarcinoma in cellular and animal models.

Abstract

BACKGROUND:

Our previous study has shown a prolonged retention and accumulation of Zn-pheophorbide a, a water-soluble derivative of chlorophyll a, in tumor tissue (Szczygiel et al. [19]). This prompted us to further evaluate the phototherapeutic potential of this photosensitizer of excellent physicochemical properties.

METHODS:

Cellular uptake of Zn-pheophorbide, its localization in cells, cytotoxicity, phototoxicity and cell death mechanisms were studied in human adenocarcinoma cell lines: A549, MCF-7 and LoVo. The PDT efficacy was tested against A549 tumors growing in nude mice.

RESULTS:

Zn-pheophorbide a even at very low concentrations (∼1×10(-6)M) and at low light doses (5J/cm(2)) causes a strong photodynamic effect, leading to 100% cell mortality. Confocal microscopy showed that in contrast to most derivatives of chlorophyll, Zn-pheophorbide a does not localize to mitochondria. The photodynamic effects and the cell death mechanisms of Zn-pheophorbide a, its Mg analog (chlorophyllide a) and Photofrin were compared on the A549 cells. Zn-pheophorbide a showed the strongest photodynamic effect, at low dose killing all A549 cells via apoptosis and necrosis. The very high anti-cancer potential of Zn-pheophorbide was confirmed in a photodynamic treatment of the A549 tumors. They either regressed or were markedly inhibited for up to 4 months after the treatment, resulting, on average, in a 5-fold decrease in tumor volume.

CONCLUSION:

These results show that Zn-pheophorbide a is a very promising low-cost, synthetically easily accessible, second generation photosensitizer against human cancer.

• Authors: Monika Jakubowska, Małgorzata Szczygieł, Dominika Michalczyk-Wetula, Anna Susz, Grażyna Stochel, Martyna Elas, Leszek Fiedor, Krystyna Urbanska
• Journal: Photodiagnosis and photodynamic therapy (Photodiagnosis Photodyn Ther) Vol. 10 Issue 3 Pg. 266-77 (Sep 2013) ISSN: 1873-1597 [Electronic] Netherlands
• PMID: 23993853 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Photosensitizing Agents
• Chlorophyll
• pheophorbide a
• Zinc

Topics

• Adenocarcinoma (drug therapy, economics, pathology)
• Animals
• Cell Line, Tumor
• Chlorophyll (analogs & derivatives, economics, therapeutic use)
• Disease Models, Animal
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Photochemotherapy (economics, methods)
• Photosensitizing Agents (economics, therapeutic use)
• Treatment Outcome
• Zinc (economics, therapeutic use)