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Nuclear DNA Damage and Repair in Normal Ovarian Cells Caused by Epothilone B
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 Title & Authors
Nuclear DNA Damage and Repair in Normal Ovarian Cells Caused by Epothilone B
Rogalska, Aneta; Marczak, Agnieszka;
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This study was designed to assess, whether a new chemotherapeutic microtubule inhibitor, Epothilone B (EpoB, Patupilone), can induce DNA damage in normal ovarian cells (MM14.Ov), and to evaluate if such damage could be repaired. The changes were compared with the effect of paclitaxel (PTX) commonly employed in the clinic. The alkaline comet assay technique and TUNEL assay were used. The kinetics of DNA damage formation and the level of apoptotic cells were determined after treatment with IC50 concentrations of EpoB and PTX. It was observed that PTX generated significantly higher apoptotic and genotoxic changes than EpoB. The peak was observed after 48 h of treatment when the DNA damage had a maximal level. The DNA damage induced by both tested drugs was almost completely repaired. As EpoB in normal cells causes less damage to DNA it might be a promising anticancer drug with potential for the treatment of ovarian tumors.
Apoptosis;DNA damage;Epothilone B;Paclitaxel;
 Cited by
Aogi K, Rai Y, Ito Y, et al (2013). Efficacy and safety of ixabepilone in taxane-resistant patients with metastatic breast cancer previously treated with anthracyclines: results of a phase II study in Japan. Cancer Chemotherap Pharmacol, 71, 1427-33. crossref(new window)

Attia SM (2013). Molecular cytogenetic evaluation of the mechanism of genotoxic potential of amsacrine and nocodazole in mouse bone marrow cells. J Applied Toxicol: JAT, 33, 426-33. crossref(new window)

Attia SM, Harisa GI, Abd-Allah AR, et al (2013). The influence of lentinan on the capacity of repair of DNA damage and apoptosis induced by paclitaxel in mouse bone marrow cells. J Biochemical Molecular Toxicol, 27, 370-7. crossref(new window)

Baumgart T, Kriesen S, Neels O, et al (2015). Investigation of epothilone B-induced cell death mechanisms in human epithelial cancer cells -in consideration of combined treatment with ionizing radiation. Cancer Invest.

Bollag DM, McQueney PA, Zhu J, et al (1995). Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action. Cancer Res, 55, 2325-33.

Gauler TC, Christoph DC, Fischer J, et al (2013). Phase-I study of sagopilone in combination with cisplatin in chemotherapy-naive patients with metastasised small-cell lung cancer. Eur J Cancer.

Goldar S, Khaniani MS, Derakhshan SM, et al (2015). Molecular mechanisms of apoptosis and roles in cancer development and treatment. Asian Pac J Cancer Prev, 16, 2129-44. crossref(new window)

Gong GL, Huang YY, Liu LL, et al (2015). Enhanced production of epothilone by immobilized Sorangium cellulosum in porous ceramics. J Microbiol Biotechnol.

Goodin S (2008). Novel cytotoxic agents: epothilones. American journal of health-system pharmacy: AJHP : official journal of the American Society of Health-System Pharmacists, 65, 10-5.

Ireno IC, Wiehe RS, Stahl AI, et al (2014). Modulation of the poly (ADP-ribose) polymerase inhibitor response and DNA recombination in breast cancer cells by drugs affecting endogenous wild-type p53. Carcinogenesis, 35, 2273-82. crossref(new window)

Ji YB, Chen N, Zhu HW, et al (2014). Alkaloids from beach spider lily (Hymenocallis littoralis) induce apoptosis of HepG-2 cells by the fas-signaling pathway. Asian Pac J Cancer Prev, 15, 9319-25. crossref(new window)

Lalli RC, Kaur K, Dadsena S, et al (2015). Maackia amurensis agglutinin enhances paclitaxel induced cytotoxicity in cultured non-small cell lung cancer cells. Biochimie.

Lichtner RB, Rotgeri A, Bunte T, et al (2001). Subcellular distribution of epothilones in human tumor cells. Proceed National Acad Sci United States America, 98, 11743-8. crossref(new window)

Navarrete KR, Alderete JB, Jimenez VA (2015). Structural basis for drug resistance conferred by beta-tubulin mutations: a molecular modelling study on native and mutated tubulin complexes with epothilone B. J Biomol Struct Dyn, 1-31.

Osswald C, Zipf G, Schmidt G, et al (2014). Modular construction of a functional artificial epothilone polyketide pathway. ACS Synth Biol, 3, 759-72. crossref(new window)

Raj KG, Sambantham S, Manikanadan R, et al (2014). Fungal taxol extracted from Cladosporium oxysporum induces apoptosis in T47D human breast cancer cell line. Asian Pac J Cancer Prev, 15, 6627-32. crossref(new window)

Rogalska A, Gajek A, Marczak A (2013a). Analysis of epothilone B-induced cell death in normal ovarian cells. Cell Biol Inter, 37, 1330-9. crossref(new window)

Rogalska A, Marczak A, Gajek A, et al (2013b). Induction of apoptosis in human ovarian cancer cells by new anticancer compounds, epothilone A and B. Toxicology in vitro : an international journal published in association with BIBRA, 27, 239-49. crossref(new window)

Rogalska A, Szula E, Gajek A, et al (2013c). Activation of apoptotic pathway in normal, cancer ovarian cells by epothilone B. Environmen Toxicol pharmacol, 36, 600-10. crossref(new window)

Roque DM, Bellone S, Buza N, et al (2013). Class III beta-tubulin overexpression in ovarian clear cell and serous carcinoma as a maker for poor overall survival after platinum/taxane chemotherapy and sensitivity to patupilone. American J Obstetrics Gynecol.

Sharifi S, Barar J, Hejazi MS, et al (2014). Roles of the Bcl-2/Bax ratio, caspase-8 and 9 in resistance of breast cancer cells to paclitaxel. Asian Pac J Cancer Prev, 15, 8617-22. crossref(new window)

Sharma S, Lagisetti C, Poliks B, et al (2013). Dissecting paclitaxel-microtubule association: quantitative assessment of the 2'-OH group. Biochemistry, 52, 2328-36. crossref(new window)

Singh NP, McCoy MT, Tice RR, et al (1988). A simple technique for quantitation of low levels of DNA damage in individual cells. Experimental Cell Res, 175, 184-91. crossref(new window)

Smaglo BG, Pishvaian MJ (2014). Profile and potential of ixabepilone in the treatment of pancreatic cancer. Drug Des Devel Ther, 8, 923-30.

Stengel C, Newman SP, Day JM, et al (2014). In vivo and in vitro properties of STX2484: a novel non-steroidal anticancer compound active in taxane-resistant breast cancer. Br J Cancer, 111, 300-8. crossref(new window)

Vahdat LT, Vrdoljak E, Gomez H, et al (2013). Efficacy and safety of ixabepilone plus capecitabine in elderly patients with anthracycline- and taxane-pretreated metastatic breast cancer. J Geriatr Oncol, 4, 346-52. crossref(new window)

Wang Y, Wang D, Fu Q, et al (2014). Shape-controlled paclitaxel nanoparticles with multiple morphologies: rod-shaped, worm-like, spherical, and fingerprint-like. Mol Pharm, 11, 3766-71. crossref(new window)

Winsel S, Sommer A, Eschenbrenner J, et al (2011). Molecular mode of action and role of TP53 in the sensitivity to the novel epothilone sagopilone (ZK-EPO) in A549 non-small cell lung cancer cells. PloS one, 6, 19273. crossref(new window)

Wu GQ, Liu NN, Xue XL, et al (2014). Multiplex real-time PCR for RRM1, XRCC1, TUBB3 and TS mRNA for prediction of response of non-small cell lung cancer to chemoradiotherapy. Asian Pac J Cancer Prev, 15, 4153-8. crossref(new window)

Zasadil LM, Andersen KA, Yeum D, et al (2014). Cytotoxicity of paclitaxel in breast cancer is due to chromosome missegregation on multipolar spindles. Sci Transl Med, 6, 229.

Zhang B, Suer S, Livak F, et al (2012). Telomere and microtubule targeting in treatment-sensitive and treatment-resistant human prostate cancer cells. Molecular Pharmacol, 82, 310-21. crossref(new window)

Zhang LY, Li PL, Xu A, et al (2015). Involvement of GRP78 in the resistance of ovarian carcinoma cells to paclitaxel. Asian Pac J Cancer Prev, 16, 3517-22. crossref(new window)