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      Downregulation of RBBP6 variant 1 during arsenic trioxide-mediated cell cycle arrest and curcumin-induced apoptosis in MCF-7 breast cancer cells

      1 , 1 , * , 1
      Future Science OA
      Future Science Ltd
      apoptosis, arsenic trioxide, breast cancer, G2/M arrest, RBBP6, splicing

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          To determine the expression patterns of the RBBP6 spliced variants during arsenic trioxide-mediated cell cycle arrest and curcumin-induced apoptosis in MCF-7 cells.

          Materials & methods:

          As 2O 3 and curcumin were used to study cytotoxicity, cell cycle arrest, apoptosis and the expression of RBBP6 variants. The MUSE Cell Analyser was used to analyze cell cycle arrest, apoptosis and multicaspase activity while apoptosis was further confirmed using microscopy. Semi-quantitative RT-PCR was employed to quantitate the expression of the RBBP6 variants.


          This study showed that the MCF-7 cells expressed RBBP6 variant 1 but lacked both variant 2 and variant 3. Both As 2O 3 and curcumin significantly downregulated RBBP6 variant 1 (p < 0.001).


          RBBP6 variants are promising therapeutic targets.

          Lay abstract

          Understanding how breast cancer develops remains to be fully understood. It is known that genes play a pivotal role in the carcinogenesis process. The RBBP6 gene, which has different variants, has been reported to be involved in cancer development but it remains unclear which RBBP6 product is involved in cancer development. This study has demonstrated that there are RBBP6 variants that are pro-carcinogenic and those that are anti-carcinogenic. This study further showed that arsenic trioxide and curcumin lowered the expression of the RBBP6 splice variant 1 in MCF-7 breast cancer cells. Therefore, targeting RBBP6 variants for future drug development is a promising strategy.

          Most cited references26

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          Cancer statistics, 2015.

          Each year the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the National Cancer Institute (Surveillance, Epidemiology, and End Results [SEER] Program), the Centers for Disease Control and Prevention (National Program of Cancer Registries), and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. A total of 1,658,370 new cancer cases and 589,430 cancer deaths are projected to occur in the United States in 2015. During the most recent 5 years for which there are data (2007-2011), delay-adjusted cancer incidence rates (13 oldest SEER registries) declined by 1.8% per year in men and were stable in women, while cancer death rates nationwide decreased by 1.8% per year in men and by 1.4% per year in women. The overall cancer death rate decreased from 215.1 (per 100,000 population) in 1991 to 168.7 in 2011, a total relative decline of 22%. However, the magnitude of the decline varied by state, and was generally lowest in the South (∼15%) and highest in the Northeast (≥20%). For example, there were declines of 25% to 30% in Maryland, New Jersey, Massachusetts, New York, and Delaware, which collectively averted 29,000 cancer deaths in 2011 as a result of this progress. Further gains can be accelerated by applying existing cancer control knowledge across all segments of the population. © 2015 American Cancer Society.
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            Induction of autophagic cell death in malignant glioma cells by arsenic trioxide.

            Recent clinical data shows that arsenic trioxide (As(2)O(3)) causes remission in patients with acute promyelocytic leukemia and multiple myeloma without severe side effects. Laboratory data suggest that As(2)O(3) induces apoptosis or cell differentiation of hematopoietic or solid tumor cells. To date, there has been no study on the effects of As(2)O(3) on glioma cells. In this study, we investigated the in vitro effect of As(2)O(3) on cell growth inhibition and cell death mechanisms in human glioma cells. As(2)O(3) significantly inhibited the proliferation of all six of the glioma cell lines (U373, U87, U251, GB1, A-172, and T98G) tested in this study in a dose-dependent manner. The IC(50) of As(2)O(3) for all of the tumor cell lines was <2 micro M. Previous studies have shown that this is a clinically safe concentration. Treatment with 2 micro M As(2)O(3) induced G(2)/M arrest in all of the glioma cell lines. Autophagy (programmed cell death type II), but not apoptosis (programmed cell death type I), was detected by electron microscopy in U-373-MG cells treated with 2 micro M As(2)O(3). Caspase inhibitors did not halt As(2)O(3)-induced cell death. Furthermore, combination of As(2)O(3) with bafilomycin A1 autophagy inhibitor enhanced the antitumor effect of As(2)O(3) through induction of apoptosis. These findings suggest that As(2)O(3) at a clinically safe concentration may be an effective chemotherapeutic agent for malignant gliomas.
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              MCF-7 breast carcinoma cells do not express caspase-3.


                Author and article information

                Future Sci OA
                Future Sci OA
                Future Science OA
                Future Science Ltd (London, UK )
                30 July 2019
                September 2019
                30 July 2019
                : 5
                : 8
                : FSO409
                [1 ]Department of Biochemistry, Microbiology, & Biotechnology, University of Limpopo, Private Bag x1106, Sovenga, 0727, Polokwane, South Africa
                Author notes
                [* ]Author for correspondence: Tel.: +27 15 268 3019; Zukile.Mbita@ 123456ul.ac.za
                Author information
                © 2019 Zukile Mbita

                This work is licensed under the Creative Commons Attribution 4.0 License

                : 03 April 2019
                : 07 June 2019
                : 30 July 2019
                Page count
                Pages: 17
                Research Article

                apoptosis,arsenic trioxide,breast cancer,g2/m arrest,rbbp6,splicing


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