Open AccessEnhancement of radiation‐induced apoptosis by Podophyllum hexandrum
Author(s) -
Kumar I. Prem,
Rana S. V. S.,
Samanta N.,
Goel H. C.
Publication year - 2003
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1211/0022357021738
Subject(s) - podophyllum , apoptosis , medicine , podophyllotoxin , biology , chemistry , biochemistry , stereochemistry
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 μM 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.