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Biomedical subjects

M Athar

Publications and source records attributed to M Athar.

94 records · Page 6Linked to original sources
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Ferrochelatase, a novel target for photodynamic therapy of cancer.

This study was designed to investigate the hypothesis that the inhibition of ferrochelatase will cause in situ build up of high concentrations of protoporphyrin-IX which may act as a putative agent for photodestruction of cancer cells. The parenteral administration of lead acetate, a known inhibitor of ferrochelatase, to mice bearing cutaneous tumors (papillomas and carcinomas) caused a six-fold enhancement in the concentration of protoporphyrin-IX in tumors within a period of one month. Forty-eight hours after the second injection of lead, mice were exposed to visible light, at a light dose of about nine kilo lux for a period of one hour (in four sittings of fifteen minutes each keeping a gap of ten minutes between two exposures). A significant reduction in tumor size was observed starting as early as day one following the treatment. Continuous treatment for six consecutive days resulted in almost complete ablation of the tumor mass in most of the animals. Complete regression of the tumors was observed at two to three days following the first exposure. Our observations on in situ accumulation of protoporphyrin-IX by heme-biosynthesis inhibition represent a novel method for photodynamic therapy of cancer cells. It is important to emphasize that lead is a fairly toxic agent and developing a non-toxic agent is one of our future goals.

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Chemopreventive effects of green tea polyphenols correlate with reversible induction of p57 expression.

Green tea polyphenols are known to induce apoptosis in certain types of tumor cells. However, the mechanism(s) that enables normal cells to evade the apoptotic effect is still not understood. In this study, Western blot analysis combined with cycloheximide treatment was used to examine the effects of green tea polyphenols on the expression levels of p57, a cyclin-dependent kinase and apoptosis inhibitor, in normal human keratinocytes and in the oral carcinoma cell lines SCC25 and OSC2. The results showed that the most potent green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), induced p57 in normal keratinocytes in a dosage- and time-dependent manner, while the levels of p57 protein in oral carcinoma cells were unaltered. The differential response in p57 induction was consistent with the apoptosis status detected by annexin V assay. The data suggest that the chemopreventive effects of green tea polyphenols may involve p57-mediated cell cycle regulation in normal epithelial cells.

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Novel copper superoxide dismutase mimics and damage mediated by O2.-.

Metabolites of oxygen such as superoxide anions (O2.-), hydrogen peroxide (H2O2), and hydroxyl radicals (OH.) are potentially damaging to biological systems. Univalent reduction of oxygen produces O2.-, which may be converted to H2O2 and OH(.). The biological damage mediated by O2.- can be attenuated by a cytosolic copper- and zinc-containing enzyme known as superoxide dismutase (SOD). Certain transition metal complexes having properties similar to SOD may be useful in suppressing such damage. However, known complexes have either been ineffective in vivo or may have toxic side effects. We prepared mixed-ligand copper complexes of polyamine using biomolecules such as pyridine or imidazoles as secondary ligands. The choice of polyamines and biomolecules was made with the aim of producing products with low toxicity. Our studies suggest that these copper complexes act as mimics of SOD in a variety of O2.(-)-generating systems and may be effective SOD mimics for their usage to abrogate such an injury in biological systems. This manuscript provides a brief state-of-the-art review on SOD mimics including our own studies.

Amino Acid Sequence↗