Screening for inhibitors from microbial secondary metabolites for photodynamic therapy and glycogen synthase kinase-3β (GSK-3β)

Kumuda Suppayah, (2007) Screening for inhibitors from microbial secondary metabolites for photodynamic therapy and glycogen synthase kinase-3β (GSK-3β). Universiti Malaysia Sabah. (Unpublished)

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Abstract

Photodynamic Therapy, a promising novel treatment for cancer, is a technique based on the preferential accumulation of photosensitizers in tumour cells. Following irradiation with appropriate light wavelength, reactive oxygen species (102) is generated which leads to apoptosis of the tumour cells. Presently an ideal photosensitizer with regards to chemical purity, tumour selectivity, chemical and physical stability as well as rapid body clearance has not been found. GSK-3β, a serine/threonine protein kinase has been found highly active in some tumours, namely colorectal cancer. GSK-3β has been associated with tumour cell survival and proliferation, where inhibition causes apoptosis of the tumour cell. This research focused on the possibility of fungal secondary metabolites having potential photosensitizers and GSK-3β inhibitors. 13 pure cultures of fungi were selected from stock cultures of fungi originating from Sabah' s tropical rain forests. These fungi strains produced pigmented secondary metabolites and were non-toxic to Saccharomyces cereviseae. These pure strains were grown aerobically to produce secondary metabolites. The acetone extract of these microbes were screened for photocytotoxic activity against a human leukaemic cell line HL60 using an MTT -based cell viability assay and also for GSK-3β inhibitors using a mutant yeast strain H10075. All extracts exhibited marginal photocytotoxicity at 20 μg/ml with no cytotoxicity when cells were kept in the dark, while for GSK-3β screening, only one strain H9042 showed marginal inhibition of yeast H10075 when it was incubated at 37°C without inhibiting at 25°C. One strain, H9969 W was chosen for investigation as PDT photosensitizers and partially purified fractions tested showed slight increment in activity by 2.6%. Further investigation on the potential of H9969 Was a photosensitizer is worth pursuing using pure compounds of H9969 W.

Item Type: Academic Exercise
Uncontrolled Keywords: Photodynamic Therapy, cancer, tumour cell, photosensitizer, acetone extract, mutant yeast strain, photocytotoxic activity
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: SCHOOL > School of Science and Technology
Depositing User: MDM SITI AZIZAH IDRIS
Date Deposited: 27 Feb 2014 03:00
Last Modified: 12 Oct 2017 04:10
URI: http://eprints.ums.edu.my/id/eprint/8329

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