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

Singh, Pankaj Kumar; Kumar, Raj; Sharma, Ashok; Arora, Rajesh; Chawla, Raman; Jain, Swatantra Kumar; Tripathi, R. P.; Sharma, Rakesh

doi:10.1093/ecam/neq059

Cited by 7 publications

(8 citation statements)

References 40 publications

(61 reference statements)

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“…HepG2 (wtp53, carrying wild-type p53), Hep3B (p53 null, lacking p53) and MHCC97L (mutp53, harboring mutant p53) human hepatoma cell lines [28], [29] were obtained from the Cell Institute of Shanghai (Academia Sinica, Shanghai, China). Cells were maintained at 37°C in a humidified incubator under 5% CO 2 and grown in Dulbecco’s modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum, 50 mg/ml penicillin/streptomycin.…”

Section: Methodsmentioning

confidence: 99%

Silencing of APE1 Enhances Sensitivity of Human Hepatocellular Carcinoma Cells to Radiotherapy In Vitro and in a Xenograft Model

et al. 2013

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Resistance to radiotherapy is a key limitation for the treatment of human hepatocellular carcinoma (HCC). To overcome this problem, we investigated the correlation between radioresistance and the human apurinic/apyrimidinic endonuclease (APE1), a bifunctional protein, which plays an important role in DNA repair and redox regulation activity of transcription factors. In the present study, we examined the radiosensitivity profiles of three human HCC cell lines, HepG2, Hep3B, and MHCC97L, using the adenoviral vector Ad5/F35-mediated APE1 siRNA (Ad5/F35-siAPE1). The p53 mutant cell lines MHCC97L showed radioresistance, compared with HepG2 and Hep3B cells. APE1 was strongly expressed in MHCC97L cells and was induced by irradiation in a dose-dependent manner, and Ad5/F35-siAPE1 effectively inhibited irradiation-induced APE1 and p53 expression. Moreover, silencing of APE1 significantly potentiated the growth inhibition and apoptosis induction by irradiation in all tested human HCC cell lines. In addition, Ad5/F35-siAPE1 significantly enhanced inhibition of tumor growth and potentiated cell apoptosis by irradiation both in HepG2 and MHCC97L xenografts. In conclusion, down regulation of APE1 could enhance sensitivity of human HCC cells to radiotherapy in vitro and in vivo.

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Section: Methodsmentioning

confidence: 99%

Silencing of APE1 Enhances Sensitivity of Human Hepatocellular Carcinoma Cells to Radiotherapy In Vitro and in a Xenograft Model

et al. 2013

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“…Our earlier studies of Podophyllum hexandrum were predominantly focused on the radioprotective efficacy of its whole or semi‐purified extracts in mouse models and in various cell lines [Shukla et al, ; Gupta et al, ; Singh et al, ]. In contrast, the current study examines the efficacy of a new formulation, termed G‐002M, generated by combining just three active compounds extracted from Podophyllum hexandrum (G‐002M).…”

Section: Introductionmentioning

confidence: 99%

Modification of radiation‐induced DNA double strand break repair pathways by chemicals extracted from Podophyllum hexandrum: An in vitro study in human blood leukocytes

Srivastava

Shukla

Yashavarddhan

et al. 2014

Environ and Mol Mutagen

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Radiation exposure is a serious threat to biomolecules, particularly DNA, proteins and lipids. Various exogenous substances have been reported to protect these biomolecules. In this study we explored the effect of pre-treatment with G-002M, a mixture of three active derivatives isolated from the rhizomes of Podophyllum hexandrum, on DNA damage response in irradiated human blood leukocytes. Blood was collected from healthy male volunteers, preincubated with G-002M and then irradiated with various doses of radiation. Samples were analyzed using flow cytometry to quantify DNA double strand break (DSB) biomarkers including γ-H2AX, P53BP1 and levels of ligase IV. Blood samples were irradiated in vitro and processed to determine time and dose-dependent kinetics. Semiquantitative RT-PCR was performed at various time points to measure gene expression of DNA-PKcs, Ku80, ATM, and 53BP1; each of these genes is involved in DNA repair signaling. Pre-treatment of blood with G-002M resulted in reduction of γ-H2AX and P53BP1 biomarkers levels and elevated ligase IV levels relative to non-G-002M-treated irradiated cells. These results confirm suppression in radiation-induced DNA DSBs. Samples pre-treated with G-002M and then irradiated also showed significant up-regulation of DNA-PKcs and Ku80 and downregulation of ATM and 53BP1 gene expressions, suggesting that G-002M plays a protective role against DNA damage. The protective effect of G-002M may be due to its ability to scavange radiation-induced free radicals or assist in DNA repair. Further studies are needed to decipher the role of G-002M on signaling molecules involved in radiation-induced DNA damage repair pathways.

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“…To investigate the affects of SQGD on modulation of radiation‐induced apoptosis, cell cycle perturbations and DNA damage, protein expression analysis was carried out. Previous studies have established the role of functional P53 protein in the cell cycle regulation and apoptosis induction (Burger et al, ; Wilson et al, ; Kumar et al, ; Singh et.al., ) under various kinds of stresses. In the current study, high level of P53 expression was observed in the mice treated with SQGD before irradiation at 24 h compared with untreated control; however, expression levels of P53 was found to be remained at lower side at all tested time points when compared with the irradiated mice [Fig.…”

Section: Discussionmentioning

confidence: 99%

“…To overcome the radiation‐induced damage, several drugs and formulations such as amifostine (Andrieu et al, ), cysteamine, MPG (Routh et al, ), LPS, and CBLB 502 (Burdelya et al, ) of natural and chemical origin have been evaluated for their radioprotective efficacy in vitro and in vivo models. Several natural plant extracts such as Podophyllum hexandrum, Rhodiola, Hippophae rhamnoides, Tinospora cordifolia, Ocimum sanctum, Psoralea corylifolia (Arora et al, ; Kumar,et al, b; Chawla et al, ; Singh et al, b; Chawla et al, ; Singh et al, ; Sharma et al, ), and so on have also been studied for their radioprotective activities. However, due to associated toxicity along with their efficacious doses, search for nontoxic or relatively less toxic radioprotective agents is continued.…”

Section: Introductionmentioning

confidence: 99%

A semiquinone glucoside derivative provides protection to male reproductive system of the mice against gamma radiation toxicity

Patel

Bansal

Mishra

et al. 2012

Environmental Toxicology

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Present investigation was carried out to evaluate the radioprotective efficacy of a novel Semiquinone glucoside derivative (SQGD), isolated from Bacillus sp. INM-1, in the male reproductive system of BALB/c mice. Animals were administered 50 mg/kg b.wt. (i.p.) SQGD 2 h before whole body γ-irradiation (10 Gy). Radiation-induced cellular toxicity and its modulation by SQGD pretreatment was evaluated in the mice testes by quantitative histological and protein expression analysis. SQGD pretreatment protects irradiated mice from radiation-induced testicular atrophy and germ cells degeneration, which may lead to emptiness of seminiferous tubules. Significant decrease in P53 and P21((Cip/WAF-1)) expression was observed in the irradiated mice pretreated (2 h) by SQGD at 6 h compared with only irradiated mice. However, contrary to P53, expressions of P21 at latter time, that is, 24-72 h was found to be increased significantly in the irradiated mice pretreated by SQGD. Significant increase in the intact PARP-1 protein expression were observed in the testes of the mice pretreated by SQGD 2 h before irradiation at 24-72 h compared with the only irradiated mice, whereas significant increase in PARP-1 cleaved fragment was noticed at 24 h. Similarly, significant increase in NF-kB and BCL-2/BAX expressions ratio was noticed in SQGD-treated mice (± irradiation) compared with irradiated mice, suggested a role of SQGD in the activation of prosurvival signaling in the testicular germinal cells population of the irradiated mice and thus contributed to protection against lethal γ-irradiation.

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

Cited by 7 publications

References 40 publications

Silencing of APE1 Enhances Sensitivity of Human Hepatocellular Carcinoma Cells to Radiotherapy In Vitro and in a Xenograft Model

Silencing of APE1 Enhances Sensitivity of Human Hepatocellular Carcinoma Cells to Radiotherapy In Vitro and in a Xenograft Model

Modification of radiation‐induced DNA double strand break repair pathways by chemicals extracted from Podophyllum hexandrum: An in vitro study in human blood leukocytes

A semiquinone glucoside derivative provides protection to male reproductive system of the mice against gamma radiation toxicity

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