Transcript Slides

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