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

Jakubowska, Monika, Szczygiel, Malgorzata, Michalczyk-Wetula, Dominika, Susz, Anna, Stochel, Grazyna, Elas, Martyna, Fiedor, Leszek and Urbanska, Krystyna 2013. Zinc-pheophorbide a—Highly efficient low-cost photosensitizer against human adenocarcinoma in cellular and animal models. Photodiagnosis and Photodynamic Therapy 10 (3) , pp. 266-277. 10.1016/j.pdpdt.2012.12.004

Full text not available from this repository.

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 (5 J/cm2) 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. Keywords

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	Zn-pheophorbide; Human adenocarcinoma; Photodynamic therapy
Publisher:	Elsevier
ISSN:	1572-1000
Last Modified:	12 Jun 2019 03:00
URI:	https://orca.cardiff.ac.uk/id/eprint/66574

Citation Data

Cited 19 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item