Enhancement of radiation-induced apoptosis by Podophyllum hexandrum.
The aqueous extract of Podophyllum hexandrum (RP-1), which has been recently reported to manifest radioprotective and anti-tumour properties, has been investigated for its mode of action. RP-1, under in-vitro conditions dose-dependently chelated metal ions, inhibited radiation or metal ion-induced hydroxyl radicals and lipid peroxidation and scavenged superoxide anions. Intraperitoneal administration of RP-1 to mice pre-irradiation (10 Gy) induced more DNA fragmentation and lipid peroxidation in thymocytes maximally at 4 and 8 h, respectively, in comparison with RP-1 treatment or irradiation. Flow-cytometric quantification of sub-diploid peak, oligonucleosomal cleavage assay (ladder) and depletion of total thiols also corroborated the ability of RP-1 to enhance radiation-induced apoptosis. RP-1 in presence of 100 microM CuSO(4) induced strand breaks in plasmid DNA and addition of metal chelators (EDTA and deferoxamine) inhibited the strand scission. Treatment with a major constituent of RP-1, podophyllin, did not cause strand breaks, but isolated constituents of RP-1, quercetin or podophyllotoxin, induced strand breaks. Depending on its concentration in the milieu, RP-1 acted as a pro- or antioxidant modifying the radiation-induced apoptosis and therefore could be exploited for cancer management.
Prem Kumar
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Department of Radiation Biology, Institute of Nuclear Medicine and Allied Sciences, Brig S. K. Majumdar Marg, Delhi, India.
Rana
S V S
SV
Samanta
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N
Goel
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HC
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002614:Chelating Agents / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D053938:DNA Fragmentation / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D005720:Gamma Rays; D017665:Hydroxyl Radical / Q000378:metabolism; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D011035:Podophyllum / Q000737:chemistry*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D027343:Rhizome / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D002614:Chelating Agents; D010936:Plant Extracts; D011838:Radiation-Sensitizing Agents; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D017665:Hydroxyl Radical