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ABILITY OF ACTIVATED ZnPcSmix TO INDUCE CELL DEATH IN HUMAN BREAST CANCER CELLS I.Tynga, N. Houreld and H. Abrahamse SAIP Conference, 10 July 2012 Background • Cancer is the second cause of death worldwide after heart-related conditions. • Many types of cancer exist but breast cancer is the most diagnosed and the principal cancer faced by women worldwide. Calin and Parasca (2006), J Optoelectron Adv M 8(3) van Zyl et al., (2012), PHCFM 4(1) Cancer • Cancer cells grow out of control and instead of dying , they continue to grow and form abnormal cells. • It is believed that cancer can be overcome through research, which aims to identify and develop anti-cancer means to deal with the condition. American Cancer Society (2011) Timeline of Cancer -3000 -2000 Egyptian Mummies Evidences of cancer found in mummies from -3000 -1000 Egyptian papyruses (-1600) Treatment of certain cancers Breast cancer may be one of the oldest in Human Cancer Council Victoria (2011) 0 1000 Incas of Peru (-400) Evidences of cancer in mummies of preColumbians Hippocrates (-300) Father of Medicine named ranges of tumours as carcinos 2000 Understanding Cancer (500-1500) Little progress was made in understanding cancer Cancer Therapies 1. 2. 3. 4. Chemotherapy Radiation therapy Surgery Immunotherapy • In responses to numerous palliative and side-effects due to non specific treatment to cancer cells. In early 1980s, a cancer treatment involving a photosensitizer (PS), light and oxygen known as Photodynamic Therapy (PDT) was developed. • Karpozilos and Pavlidis (2004), Eur J Cancer 40 Marx (1989), Science 246 Manoto and Abrahamse (2011) Lasers in Med Sci 43 Photodynamic Cancer Therapy (PDT) • PDT is a promising and an efficient because this treatment is neoplastic selective. • PDT has been approved and recommended in the most developed countries. • • The accessibility of cancer or tumour cells to laser light. Castano et al., (2004) Photodiagn Photodyn 1 Mroz et al., (2010) J Pone 5(12) Photosensitizers (PS) • First approved PS in human treatment was photophryin. • More PSs are being developed with new and improved characteristics based on photophyrin. M=Al/Zn/Ge Levy (1994),Semin Oncol 2(15) Manoto and Abrahamse (2011),Lasers in Med Sci 43 AIMS • To identify cellular localization of ZnPcSmix in Human breast cancer cells. • To determine optimal laser fluency and ZnPcSmix concentration. • To identify the induced cell death pathway subsequent to PDT. Materials and Methods MCF-7 ZnPcSmix Irradiation 0.05, 0.1, 0.5 and 1μM 5, 10 and 15 J/cm2 Diode laser 680 nm Output power 45 mW Spot size was 9.1 cm2 Localization Viability Proliferation Cytotoxicity Cell Death Fluorescence Staining ATP Trypan blue AlamarBlue LDH Flow Cytometry Irradiation times 16 min 50 s (5 J/cm2) 33 min 40 s (10 J/cm2) 50 min 30 s (15 J/cm2) Localization Cell Viability Proliferation and Cytotoxicity Flow Cytometry Conclusion • Mitochondria, lysosomes and golgi apparatus are the primary sites of ZnPcSmix. • 0.5 µM ZnPcSmix and 10 J/cm2 laser were used for cell death study. • Activated ZnPcSmix induced cell death in human breast cancer cells by apoptosis. • ZnPcSmix-mediated PDT is an effective inducer of cell death. ACKNOWLEDGEMENTS