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Article

Induction of apoptotic cell death by betulin in multidrug-resistant human renal carcinoma cells

  • Authors:
    • Nam-Hui Yim
    • Young Pil Jung
    • Aeyung Kim
    • Taesoo Kim
    • Jin Yeul Ma
  • View Affiliations / Copyright

    Affiliations: Korean Medicine (KM)-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine (KIOM), Yuseong-gu, Daejeon 305-811, Republic of Korea
  • Pages: 1058-1064
    |
    Published online on: June 9, 2015
       https://doi.org/10.3892/or.2015.4045
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Abstract

Betulin, a triterpene from the bark of various species of birch tree, has various biological effects, including antiviral, antifungal and anticancer activities. The aim of the present study was to elucidate the mechanisms underlying the apoptotic effect of betulin in RCC4 multidrug-resistant human renal carcinoma cells. To evaluate anticancer activity, we performed cell viability and caspase activity assays, a proteome profiler array and western blot analysis in RCC4 cells. Betulin significantly decreased RCC4 cell viability in a time- and concentration-dependent manner. Betulin activated caspase family proteins, including caspase-3, -7, -8 and -9, and increased the expression of apoptosis-related proteins, including PARP and Bcl-2 family members. In an apoptosis array, betulin activated the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors TRAIL R1/DR4 and R2/DR5, and tumour necrosis factor receptor 1 (TNFR1), suggesting that betulin treatment leads to induction of apoptosis through both intrinsic and extrinsic apoptosis pathways in RCC4 cells. Notably, betulin significantly enhanced cytotoxicity and PARP cleavage in etoposide-treated RCC4 cells, and downregulated the expression of multidrug resistance protein 1 (MDR1). Taken together, our findings suggest that the anticancer effects of betulin involve induction of apoptosis and sensitisation of RCC4 cells, providing potentially useful information applicable to the use of betulin in renal cancer treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Yim N, Jung YP, Kim A, Kim T and Ma JY: Induction of apoptotic cell death by betulin in multidrug-resistant human renal carcinoma cells. Oncol Rep 34: 1058-1064, 2015.
APA
Yim, N., Jung, Y.P., Kim, A., Kim, T., & Ma, J.Y. (2015). Induction of apoptotic cell death by betulin in multidrug-resistant human renal carcinoma cells. Oncology Reports, 34, 1058-1064. https://doi.org/10.3892/or.2015.4045
MLA
Yim, N., Jung, Y. P., Kim, A., Kim, T., Ma, J. Y."Induction of apoptotic cell death by betulin in multidrug-resistant human renal carcinoma cells". Oncology Reports 34.2 (2015): 1058-1064.
Chicago
Yim, N., Jung, Y. P., Kim, A., Kim, T., Ma, J. Y."Induction of apoptotic cell death by betulin in multidrug-resistant human renal carcinoma cells". Oncology Reports 34, no. 2 (2015): 1058-1064. https://doi.org/10.3892/or.2015.4045
Copy and paste a formatted citation
x
Spandidos Publications style
Yim N, Jung YP, Kim A, Kim T and Ma JY: Induction of apoptotic cell death by betulin in multidrug-resistant human renal carcinoma cells. Oncol Rep 34: 1058-1064, 2015.
APA
Yim, N., Jung, Y.P., Kim, A., Kim, T., & Ma, J.Y. (2015). Induction of apoptotic cell death by betulin in multidrug-resistant human renal carcinoma cells. Oncology Reports, 34, 1058-1064. https://doi.org/10.3892/or.2015.4045
MLA
Yim, N., Jung, Y. P., Kim, A., Kim, T., Ma, J. Y."Induction of apoptotic cell death by betulin in multidrug-resistant human renal carcinoma cells". Oncology Reports 34.2 (2015): 1058-1064.
Chicago
Yim, N., Jung, Y. P., Kim, A., Kim, T., Ma, J. Y."Induction of apoptotic cell death by betulin in multidrug-resistant human renal carcinoma cells". Oncology Reports 34, no. 2 (2015): 1058-1064. https://doi.org/10.3892/or.2015.4045
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