期刊
PHYTOTHERAPY RESEARCH
卷 26, 期 5, 页码 734-742出版社
WILEY
DOI: 10.1002/ptr.3607
关键词
apoptosis; breast cancer; MCF-7; Pheophorbide a; photodynamic therapy
资金
- Research Grant Council of Hong Kong [464507]
- South China National Research Centre for Integrated Biosciences in Collaboration with Zhongshan University [1902006]
- State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK)
- Ming Lai Foundation
- International Association of Lions Clubs District - Hong Kong
- Macau Tam Wah Ching Chinese Medicine Resource Centre in Institute of Chinese Medicine, CUHK
- CUHK
Breast cancer is conventionally treated by surgery and radiotherapy, with adjuvant chemotherapy and hormonotherapy as supplementary treatments. However, such treatments are associated with adverse side effects and drug resistance. In this study, Pheophorbide a (Pa), a photosensitizer isolated from Scutelleria barbata, was analysed for its antiproliferative effect on human breast tumour cells. The IC (inhibitory concentration)50 of the combined treatment of Pa and photodynamic therapy (Pa-PDT) on human breast tumour MCF-7 cells was 0.5?mu m. Mechanistic studies in MCF-7 cells demonstrated that Pa was localized in the mitochondria, and reactive oxygen species were found to be released after Pa-PDT. Apoptosis was the major mechanism responsible for the tumour cell death, and mitochondrial membrane depolarization and cytochrome c release highlighted the role of mitochondria in the apoptotic mechanism. Up-regulation of tumour suppressor protein p53, cleavage of caspase-9 and poly (ADP-ribose) polymerase suggested that the caspase-dependent pathway was induced, while the release of apoptosis-inducing factors demonstrated that the apoptosis was also mediated by the caspase-independent mechanism. In vivo study using the mouse xenograft model showed a significant inhibition of MCF-7 tumour growth by Pa-PDT. Together, the results of this study provide a basis for understanding and developing Pa-PDT as a cure for breast cancer. Copyright (c) 2011 John Wiley & Sons, Ltd.
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