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Article Open Access

Japanese apricot extract (MK615) potentiates bendamustine-induced apoptosis via impairment of the DNA damage response in lymphoma cells

  • Authors:
    • Masaya Inoue
    • Yoshio Honma
    • Takeshi Urano
    • Junji Suzumiya
  • View Affiliations / Copyright

    Affiliations: Department of Oncology/Hematology, Faculty of Medicine, Shimane University, Izumo, Shimane 693‑8501, Japan, Department of Biochemistry, Faculty of Medicine, Shimane University, Izumo, Shimane 693‑8501, Japan
    Copyright: © Inoue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 792-800
    |
    Published online on: May 19, 2017
       https://doi.org/10.3892/ol.2017.6219
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Abstract

Bendamustine, a hybrid molecule of a purine analog and alkylator, induces cell death by the activation of apoptosis and the DNA damage response. The agent MK615 is produced from Japanese apricot and contains a number of cyclic triterpenes that exhibit antitumor activities. In the present study, the combined effects of bendamustine and MK615 on lymphoma cells were investigated. The combined compounds synergistically induced apoptosis in all lymphoid cell lines examined. MK615 inhibited the bendamustine-induced phosphorylation of checkpoint kinase 1 and 2. As ataxia telangiectasia mutated (ATM) and ataxia telangiectasia‑ and Rad3‑related (ATR) kinases are key mediators of the DNA damage response, the effects of the combination of bendamustine and ATM/ATR inhibitors (KU‑60019 and VE‑821) on lymphoma cells were investigated. KU‑60019 and/or VE-821 potentiated bendamustine activity in all cell lines tested, but did not affect MK615 activity, suggesting that these inhibitors have the same underlying mechanism of action as that of MK615. The results of the present study suggest that it may be feasible to use ATM/ATR inhibitors in combination with bendamustine for treating malignant lymphoma.
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1 

Tageja N and Nagi J: Bendamustine: Something old, something new. Cancer Chemother Pharmacol. 66:413–423. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Hartmann M and Zimmer C: Investigation of cross-link formation in DNA by the alkylating cytostatic IMET 3106, 3393 and 3943. Biochim Biophys Acta. 287:386–389. 1972. View Article : Google Scholar : PubMed/NCBI

3 

Strumberg D, Harstrick A, Doll K, Hoffmann B and Seeber S: Bendamustine hydrochloride activity against doxorubicin-resistant human breast carcinoma cell lines. Anticancer Drugs. 7:415–421. 1996. View Article : Google Scholar : PubMed/NCBI

4 

Leoni LM, Bailey B, Reifert J, Bendall HH, Zeller RW, Corbeil J, Elliott G and Niemeyer CC: Bendamustine (Treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylating agents. Clin Cancer Res. 14:309–317. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Knauf WU, Lissichkov T, Aldaoud A, Liberati A, Loscertales J, Herbrecht R, Juliusson G, Postner G, Gercheva L, Goranov S, et al: Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol. 27:4378–4384. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Friedberg JW, Cohen P, Chen L, Robinson KS, Forero-Torres A, La Casce AS, Fayad LE, Bessudo A, Camacho ES, Williams ME, et al: Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: Results from a phase II multicenter, single-agent study. J Clin Oncol. 26:204–210. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Ohmachi K, Niitsu N, Uchida T, Kim SJ, Ando K, Takahashi N, Takahashi N, Uike N, Eom HS, Chae YS, et al: Multicenter phase II study of bendamustine plus rituximab in patients relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 31:2103–2109. 2013. View Article : Google Scholar : PubMed/NCBI

8 

McCloskey JK, Broome CM and Cheson BD: Safe and effective treatment of aggressive non-Hodgkin lymphoma with rituximab and bendamustine in patients with severe liver impairment. Clin Adv Hematol Oncol. 11:184–188. 2013.PubMed/NCBI

9 

Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, et al: Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: An open-label, multicentre, randomized, phase 3 non-inferiority trial. Lancet. 381:1203–1210. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Hiraoka N, Kikuchi J, Yamauchi T, Koyama D, Wada T, Uesawa M, Akutsu M, Mori S, Nakamura Y, Ueda T, et al: Purine analog-like properties of bendamustine underlie rapid activation of DNA damage response and synergistic effects with pyrimidine analogues in lymphoid malignancies. PLoS One. 9:e906752014. View Article : Google Scholar : PubMed/NCBI

11 

Visco C, Finotto S, Zambello R, Paolini R, Menin A, Zanotti R, Zaja F, Semenzato G, Pizzolo G, D'Amore ES and Rodeghiero F: Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation. J Clin Oncol. 31:1442–1449. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Hattori M, Kawakami K, Akimoto M, Takenaga M, Suzumiya J and Honma Y: Antitumor effect of Japanese apricot extract (MK615) on human cancer cells in vitro and in vivo through a reactive oxygen species-dependent mechanism. Tumori. 99:239–248. 2013.PubMed/NCBI

13 

Adachi M, Suzuki Y, Mizuta T, Osawa T, Adachi T, Osaka K, Suzuki K, Shiojima K, Arai Y, Masuda K, et al: The ‘Prunus mume Sieb. et Zucc’ (Ume) is a rich natural source of novel anti-cancer substance. Int J Food Prop. 10:375–384. 2007. View Article : Google Scholar

14 

Gutterman JU, La HT, Yang P, Haridas V, Gaikwad A and Marcus S: Effects of the tumor inhibitory triterpenoid avicin G on cell integrity, cytokinesis, and protein ubiquitination in fission yeast. Proc Natl Acad Sci USA. 102:pp. 12771–12776. 2005; View Article : Google Scholar : PubMed/NCBI

15 

Yamai H, Sawada N, Yoshida T, Seike J, Takizawa H, Kenzaki K, Miyoshi T, Kondo K, Bando Y, Ohnishi Y and Tangoku A: Triterpenes augment the inhibitory effects of anticancer drugs on growth of human esophageal carcinoma cells in vitro and suppress experimental metastasis in vivo. Int J Cancer. 125:952–960. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Matsushita S, Tada K, Kawahara K, Kawai K, Hashiguchi T, Maruyama I and Kanekura T: Advanced malignant melanoma responds to Prunus mume Sieb. Et Zucc (Ume) extract: Case report and in vitro study. Exp Ther Med. 1:569–574. 2010.PubMed/NCBI

17 

Niitsu N, Higashihara M and Honma Y: Human B-cell lymphoma cell lines are highly sensitive to apoptosis induced by all-trans retinoic acid and interferon-gamma. Leuk Res. 26:745–755. 2002. View Article : Google Scholar : PubMed/NCBI

18 

Weber AM and Ryan AJ: ATM and ATR as therapeutic targets in cancer. Pharmacol Ther. 149:124–138. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Ackler S, Mitten MJ, Chen J, Foster K, Jin S, Phillips DC, Schlessinger S, Wang B, Leverson JD and Boghaert ER: Navitoclax (ABT-263) and bendamustine ± rituximab induce enhanced killing of non-Hodgkin's lymphoma tumours in vivo. Br J Pharmacol. 167:881–891. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Lu B, Li J, Pan J, Huang B, Liu J and Zheng D: Everolimus enhances the cytotoxicity of bendamustine in multiple myeloma cells through a network of pro-apoptotic and cell-cycle-progression regulatory proteins. Acta Biochim Biophys Sin (Shanghai). 45:683–691. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Yang Q, Chen LS, Neelapu SS and Gandhi V: Combination of Pim kinase inhibitor SGI-1776 and bendamustine in B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 13 Suppl 2:S355–S362. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Cai B, Lyu H, Huang J, Wang S, Lee CK, Gao C and Liu B: Combination of bendamustine and etinostat synergistically inhibits proliferation of multiple myeloma cells via induction of apoptosis and DNA damage response. Cancer Lett. 335:343–350. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Kaneko N, Mitsuoka K, Amino N, Yamanaka K, Kita A, Mori M, Miyoshi S and Kuromitsu S: Combination of YM155, a surviving suppressant, with bendamustine and rituximab: A new combination therapy to treat relapse/refractory diffuse large B-cell lymphoma. Clin Cancer Res. 20:1814–1822. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Feng Y, Wang N, Zhu M, Feng Y, Li H and Tsao S: Recent progress on anticancer candidates in patents of herbal medicinal products. Recent Pat Food Nutr Agric. 3:30–48. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Fokas E, Prevo R, Hammond EM, Brunner TB, McKenna WG and Muschel RJ: Targeting ATR in DNA damage response and cancer therapeutics. Cancer Treat Rev. 40:109–117. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Inoue M, Honma Y, Urano T and Suzumiya J: Japanese apricot extract (MK615) potentiates bendamustine-induced apoptosis via impairment of the DNA damage response in lymphoma cells. Oncol Lett 14: 792-800, 2017.
APA
Inoue, M., Honma, Y., Urano, T., & Suzumiya, J. (2017). Japanese apricot extract (MK615) potentiates bendamustine-induced apoptosis via impairment of the DNA damage response in lymphoma cells. Oncology Letters, 14, 792-800. https://doi.org/10.3892/ol.2017.6219
MLA
Inoue, M., Honma, Y., Urano, T., Suzumiya, J."Japanese apricot extract (MK615) potentiates bendamustine-induced apoptosis via impairment of the DNA damage response in lymphoma cells". Oncology Letters 14.1 (2017): 792-800.
Chicago
Inoue, M., Honma, Y., Urano, T., Suzumiya, J."Japanese apricot extract (MK615) potentiates bendamustine-induced apoptosis via impairment of the DNA damage response in lymphoma cells". Oncology Letters 14, no. 1 (2017): 792-800. https://doi.org/10.3892/ol.2017.6219
Copy and paste a formatted citation
x
Spandidos Publications style
Inoue M, Honma Y, Urano T and Suzumiya J: Japanese apricot extract (MK615) potentiates bendamustine-induced apoptosis via impairment of the DNA damage response in lymphoma cells. Oncol Lett 14: 792-800, 2017.
APA
Inoue, M., Honma, Y., Urano, T., & Suzumiya, J. (2017). Japanese apricot extract (MK615) potentiates bendamustine-induced apoptosis via impairment of the DNA damage response in lymphoma cells. Oncology Letters, 14, 792-800. https://doi.org/10.3892/ol.2017.6219
MLA
Inoue, M., Honma, Y., Urano, T., Suzumiya, J."Japanese apricot extract (MK615) potentiates bendamustine-induced apoptosis via impairment of the DNA damage response in lymphoma cells". Oncology Letters 14.1 (2017): 792-800.
Chicago
Inoue, M., Honma, Y., Urano, T., Suzumiya, J."Japanese apricot extract (MK615) potentiates bendamustine-induced apoptosis via impairment of the DNA damage response in lymphoma cells". Oncology Letters 14, no. 1 (2017): 792-800. https://doi.org/10.3892/ol.2017.6219
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