Podophyllum hexandrum Fraction (REC-2006) Shows Higher Radioprotective Efficacy in the p53-Carrying Hepatoma Cell Line: A Role of Cell Cycle Regulatory Proteins

Singh, Pankaj Kumar; Kumar, Raj; Sharma, Ashok; Arora, Rajesh; Chawla, Raman; Jain, Swatantra Kumar; Sharma, Rakesh

doi:10.1177/1534735409343589

Cited by 16 publications

(27 citation statements)

References 37 publications

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“…56 Leaf extract of Aloe vera has also been demonstrated to have damage-resistant properties against radiation-induced biochemical alterations in Swiss albino mice. 57 The radioprotective property of Podophyllum hexandrum fraction (REC-2006) in p53-carrying hepatoma cell line, perhaps mediated by cell cycle regulatory proteins 58 and free radical scavenging activity and radioprotection of Caesalpinia digyna extracts 59 has been reported. More recently, the radioprotective property of a seed extract of Silymarin, with INM-7035 as its bioactive constituent 60 and the radiation mitigating effect of hydro-alcoholic extract of Saraca indica (SIE) against mice exposed to whole body γ-radiation have also been reported.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Radiation-Induced DNA Damage by Jamun, Syzygium cumini, in the Cultured Splenocytes of Mice Exposed to Different Doses of γ-Radiation

2011

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The radioprotective property of 50 mg/kg body weight jamun (Syzygium cumini) extract was studied in the cultured splenocytes of mice exposed to 0, 0.5, 1, 2, 3, or 4 Gy of γ-radiation. The spleens of irradiated mice were removed aseptically and the splenocytes were extracted from the individual spleens and cultured. The micronuclei were prepared 72 hours after irradiation in binucleate splenocytes by blocking cytokinesis with cytochalasin-B. Irradiation of mice resulted in a dose-dependent elevation in the micronucleated splenocytes. The exposure of mice not only elevated splenocytes bearing one micronucleus but also cells bearing 2 and multiple (>2) micronuclei indicating induction of complex DNA damage after irradiation. Oral treatment of mice with 50 mg/kg body weight of jamun leaf extract protected against the radiation-induced micronuclei formation. Jamun extract also protected against the formation of 2 and multiple micronuclei indicating repair or inhibition of complex DNA damage. The assessment of lipid peroxidation in mice brain homogenate has indicated a concentration dependent inhibition of lipid peroxidation by jamun extract. Studies in a cell free system revealed that jamun extract inhibited the formation of OH, O 2 −, DPPH, and ABTS + free radicals in a concentration dependent manner. Our study demonstrates that jamun extract protected mice against the radiation-induced DNA damage and inhibition of radiation-induced free radical formation may be one of the mechanisms of radioprotection.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Radiation-Induced DNA Damage by Jamun, Syzygium cumini, in the Cultured Splenocytes of Mice Exposed to Different Doses of γ-Radiation

2011

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“…Previously, we reported higher radioresistance against γ -radiation in the HepG2 (p53 ++ ) cell lines as compared with the Hep3B (p53 −− ) cell lines, indicating the plausible role of p53 in radioresistance [2]. We demonstrated that a non-polar chloroform fraction (REC-2006) of Podophyllum hexandrum , a Himalayan plant which grows at an altitude of about 4000 m in the Himalayan region, rendered nearly twice the survival (dose modification factor (DMF) = 1.72) in p53 expressing HepG2 cells, as compared with p53-negative Hep3B cells (40% survival; DMF = 1.26) [2], mainly by modulating the expression of p53.…”

Section: Introductionmentioning

confidence: 99%

Role of Apoptotic Proteins in REC‐2006 Mediated Radiation Protection in Hepatoma Cell Lines

Singh

Kumar

Sharma

et al. 2011

Evidence-Based Complementary and Alternative Medicine

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The present study was carried out to evaluate the role of apoptotic proteins in REC-2006-mediated radiation protection in hepatoma cell lines. REC-2006 treatment 2 h before irradiation strongly inhibited the cleavage of ATM and PARP-1 in HepG2 cells. The expression of nuclear apoptosis inducing factor (AIF) was found to be more inhibited (~17%) in HepG2 cells in REC-2006 + radiation-treated group. More inhibition (~33%) of cytochrome c was observed in HepG2 cells upon REC-2006 treatment 2 h prior irradiation. Similarly, significantly more (P<.05) inhibition of Apaf-1, caspase-9 and caspase-3 was observed in REC-2006 + radition-treated group in HepG2 cells. REC-2006 treatment restored the expression of ICAD in HepG2 cells; however, no restoration was observed in Hep3B cells. Lower nuclear to cytoplasmic CAD ratio was observed in HepG2 cells (~0.6) as compared with Hep3B cells (~1.2) in REC-2006 + radiation-treated group. In conclusion, REC-2006 rendered higher protection in HepG2 cells by inhibiting the expression and translocation of AIF, inhibiting the cleavage of ATM and PARP-1, restoring the expression of ICAD, inhibiting the release of cytochrome c and thus modulating the expression of Apaf-1 caspase-9 and activity of caspase-3.

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“…We observed higher expression of p21 along with lower expression of cyclin E and CDK2 in the P. hexandrum pretreated and irradiated mice as compared to irradiated mice showing delays in the G1 phase of cell cycle, which provided extra time for DNA repair or related processes [10]. No significant difference in CDK1 expression in P. hexandrum treated cell lines suggested that G2 arrest might not be the only responsible factor for P. hexandrum mediated radioprotection.…”

Section: Introductionmentioning

confidence: 58%

Radioprotective Nature of Podophyllum hexandrum (Himalayan Mayapple)

2014

Gene Technology

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Podophyllum hexandrum Fraction (REC-2006) Shows Higher Radioprotective Efficacy in the p53-Carrying Hepatoma Cell Line: A Role of Cell Cycle Regulatory Proteins

Abstract: The present study was carried out to evaluate the radioprotective efficacy of Podophyllum hexandrum fraction (REC-2006) in hepatoma cell lines having different p53 statuses. Higher radioresistance was observed in the HepG2 (p53

Cited by 16 publications

References 37 publications

Inhibition of Radiation-Induced DNA Damage by Jamun, Syzygium cumini, in the Cultured Splenocytes of Mice Exposed to Different Doses of γ-Radiation

Inhibition of Radiation-Induced DNA Damage by Jamun, Syzygium cumini, in the Cultured Splenocytes of Mice Exposed to Different Doses of γ-Radiation

Role of Apoptotic Proteins in REC‐2006 Mediated Radiation Protection in Hepatoma Cell Lines

Radioprotective Nature of Podophyllum hexandrum (Himalayan Mayapple)

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