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International Journal of Oncology
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Article

A novel anthracene derivative, MHY412, induces apoptosis in doxorubicin-resistant MCF-7/Adr human breast cancer cells through cell cycle arrest and downregulation of P-glycoprotein expression

  • Authors:
    • Umasankar De
    • Pusoon Chun
    • Wahn Soo Choi
    • Byung Mu Lee
    • Nam Deuk Kim
    • Hyung Ryong Moon
    • Jee H. Jung
    • Hyung Sik Kim
  • View Affiliations / Copyright

    Affiliations: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea, College of Pharmacy, Inje University, Gyeongnam 621-749, Republic of Korea, Institute of Biomedical Science and Technology, College of Medicine, Konkuk University, Chungju 380-701, Republic of Korea, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea
  • Pages: 167-176
    |
    Published online on: October 31, 2013
       https://doi.org/10.3892/ijo.2013.2160
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Abstract

New potential chemotherapeutic strategies are required to overcome multidrug resistance (MDR) in cancer. This study investigated the anticancer effect of a novel anthracene derivative MHY412 on doxorubicin-resistant human breast cancer (MCF-7/Adr) cells. We measured cell viability and the expression of apoptosis-related genes; in addition, the antitumor activity of MHY412 was confirmed using an in vivo tumor xenograft model. MHY412 significantly inhibited the proliferation of MCF-7/Adr and MCF-7 cells in a concentration-dependent manner. Notably, the half‑maximal inhibitory concentration (IC50) values of MHY412 in MCF-7/Adr (0.15 µM) and MCF-7 (0.26 µM) cells were lower than those of doxorubicin (MCF-7/Adr, 13.6 µM and MCF-7, 1.26 µM) after treatment for 48 h. MHY412 at low concentrations induced S phase arrest, but at high concentrations, the number of MCF-7/Adr cells in the sub-G1 phase significantly increased. MHY412-induced sub-G1 phase arrest was associated with inhibition of cyclin, cyclin‑dependent kinase 2 (CDK2) and p21 expression in MCF-7/Adr cells. MHY412 markedly reduced P-glycoprotein (P-gp) expression and increased apoptotic cell death in MCF-7/Adr cells. Cleavage of poly-ADP ribose polymerase, reduced Bcl-2 expression, and increased in cytochrome c release in MCF-7/Adr cells confirmed the above results. In addition, MHY412 markedly inhibited tumor growth in a tumor xenograft model of MCF-7/Adr cells. Our data suggest that MHY412 exerts antitumor effects by selectively modulating the genes related to cell cycle arrest and apoptosis. In particular, MHY412 is a new candidate agent for the treatment of Bcl-2 overexpressed doxorubicin-resistant human breast cancer.
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Copy and paste a formatted citation
Spandidos Publications style
De U, Chun P, Choi WS, Lee BM, Kim ND, Moon HR, Jung JH and Kim HS: A novel anthracene derivative, MHY412, induces apoptosis in doxorubicin-resistant MCF-7/Adr human breast cancer cells through cell cycle arrest and downregulation of P-glycoprotein expression. Int J Oncol 44: 167-176, 2014.
APA
De, U., Chun, P., Choi, W.S., Lee, B.M., Kim, N.D., Moon, H.R. ... Kim, H.S. (2014). A novel anthracene derivative, MHY412, induces apoptosis in doxorubicin-resistant MCF-7/Adr human breast cancer cells through cell cycle arrest and downregulation of P-glycoprotein expression. International Journal of Oncology, 44, 167-176. https://doi.org/10.3892/ijo.2013.2160
MLA
De, U., Chun, P., Choi, W. S., Lee, B. M., Kim, N. D., Moon, H. R., Jung, J. H., Kim, H. S."A novel anthracene derivative, MHY412, induces apoptosis in doxorubicin-resistant MCF-7/Adr human breast cancer cells through cell cycle arrest and downregulation of P-glycoprotein expression". International Journal of Oncology 44.1 (2014): 167-176.
Chicago
De, U., Chun, P., Choi, W. S., Lee, B. M., Kim, N. D., Moon, H. R., Jung, J. H., Kim, H. S."A novel anthracene derivative, MHY412, induces apoptosis in doxorubicin-resistant MCF-7/Adr human breast cancer cells through cell cycle arrest and downregulation of P-glycoprotein expression". International Journal of Oncology 44, no. 1 (2014): 167-176. https://doi.org/10.3892/ijo.2013.2160
Copy and paste a formatted citation
x
Spandidos Publications style
De U, Chun P, Choi WS, Lee BM, Kim ND, Moon HR, Jung JH and Kim HS: A novel anthracene derivative, MHY412, induces apoptosis in doxorubicin-resistant MCF-7/Adr human breast cancer cells through cell cycle arrest and downregulation of P-glycoprotein expression. Int J Oncol 44: 167-176, 2014.
APA
De, U., Chun, P., Choi, W.S., Lee, B.M., Kim, N.D., Moon, H.R. ... Kim, H.S. (2014). A novel anthracene derivative, MHY412, induces apoptosis in doxorubicin-resistant MCF-7/Adr human breast cancer cells through cell cycle arrest and downregulation of P-glycoprotein expression. International Journal of Oncology, 44, 167-176. https://doi.org/10.3892/ijo.2013.2160
MLA
De, U., Chun, P., Choi, W. S., Lee, B. M., Kim, N. D., Moon, H. R., Jung, J. H., Kim, H. S."A novel anthracene derivative, MHY412, induces apoptosis in doxorubicin-resistant MCF-7/Adr human breast cancer cells through cell cycle arrest and downregulation of P-glycoprotein expression". International Journal of Oncology 44.1 (2014): 167-176.
Chicago
De, U., Chun, P., Choi, W. S., Lee, B. M., Kim, N. D., Moon, H. R., Jung, J. H., Kim, H. S."A novel anthracene derivative, MHY412, induces apoptosis in doxorubicin-resistant MCF-7/Adr human breast cancer cells through cell cycle arrest and downregulation of P-glycoprotein expression". International Journal of Oncology 44, no. 1 (2014): 167-176. https://doi.org/10.3892/ijo.2013.2160
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