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Synergism of a novel MCL‑1 downregulator, acriflavine, with navitoclax (ABT‑263) in triple‑negative breast cancer, lung adenocarcinoma and glioblastoma multiforme

  • Authors:
    • Anbok Lee
    • Hyeon-Ok Jin
    • Md. Masudul Haque
    • Hee Yeon Kim
    • Hana Jung
    • Jin Hee Park
    • Ilhwan Kim
    • Joo Yeon Song
    • Hye Kyoung Yoon
    • Hyoung Kyu Kim
    • Jin Han
    • In-Chul Park
    • Kwang Seok Kim
    • Sae Gwang Park
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Busan Paik Hospital, College of Medicine, Inje University, Busan 47392, Republic of Korea, KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea, Department of Microbiology and Immunology, College of Medicine, Inje University, Busan 47392, Republic of Korea, Department of Internal Medicine, Division of Oncology, Haeundae Paik Hospital, College of Medicine, Inje University, Busan 48108, Republic of Korea, Department of Pathology, Dongnam Institute of Radiological and Medical Sciences, Busan 46033, Republic of Korea, Department of Pathology, Inje University, Busan 47392, Republic of Korea, Cardiovascular and Metabolic Disease Center, Smart Marine Therapeutic Center, College of Medicine, Inje University, Busan 47397, Republic of Korea, Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea
    Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 2
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    Published online on: December 8, 2021
       https://doi.org/10.3892/ijo.2021.5292
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Abstract

Myeloid cell leukemia sequence 1 (MCL‑1), an anti‑apoptotic B‑cell lymphoma 2 (BCL‑2) family molecule frequently amplified in various human cancer cells, is known to be critical for cancer cell survival. MCL‑1 has been recognized as a target molecule for cancer treatment. While various agents have emerged as potential MCL‑1 blockers, the present study presented acriflavine (ACF) as a novel MCL‑1 inhibitor in triple‑negative breast cancer (TNBC). Further evaluation of its treatment potential on lung adenocarcinoma and glioblastoma multiforme (GBM) was also investigated. The anticancer effect of ACF on TNBC cells was demonstrated when MDA‑MB‑231 and HS578T cells were treated with ACF. ACF significantly induced typical intrinsic apoptosis in TNBCs in a dose‑ and time‑dependent manner via MCL‑1 downregulation. MCL‑1 downregulation by ACF treatment was revealed at each phase of protein expression. Initially, transcriptional regulation via reverse transcription‑quantitative PCR was validated. Then, post‑translational regulation was explained by utilizing an inhibitor against protein biosynthesis and proteasome. Lastly, immunoprecipitation of ubiquitinated MCL‑1 confirmed the post‑translational downregulation of MCL‑1. In addition, the synergistic treatment efficacy of ACF with the well‑known MCL‑1 inhibitor ABT‑263 against the TNBC cells was explored [combination index (CI)<1]. Conjointly, the anticancer effect of ACF was assessed in GBM (U87, U251 and U343), and lung cancer (A549 and NCI‑H69) cell lines as well, using immunoblotting, cytotoxicity assay and FACS. The effect of the combination treatment using ACF and ABT‑263 was estimated in GBM (U87, U343 and U251), and non‑small cell lung cancer (A549) cells likewise. The present study suggested a novel MCL‑1 inhibitory function of ACF and the synergistic antitumor effect with ABT‑263.
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Copy and paste a formatted citation
Spandidos Publications style
Lee A, Jin H, Masudul Haque M, Kim HY, Jung H, Park JH, Kim I, Song JY, Yoon HK, Kim HK, Kim HK, et al: Synergism of a novel MCL‑1 downregulator, acriflavine, with navitoclax (ABT‑263) in triple‑negative breast cancer, lung adenocarcinoma and glioblastoma multiforme. Int J Oncol 60: 2, 2022.
APA
Lee, A., Jin, H., Masudul Haque, M., Kim, H.Y., Jung, H., Park, J.H. ... Park, S.G. (2022). Synergism of a novel MCL‑1 downregulator, acriflavine, with navitoclax (ABT‑263) in triple‑negative breast cancer, lung adenocarcinoma and glioblastoma multiforme. International Journal of Oncology, 60, 2. https://doi.org/10.3892/ijo.2021.5292
MLA
Lee, A., Jin, H., Masudul Haque, M., Kim, H. Y., Jung, H., Park, J. H., Kim, I., Song, J. Y., Yoon, H. K., Kim, H. K., Han, J., Park, I., Kim, K. S., Park, S. G."Synergism of a novel MCL‑1 downregulator, acriflavine, with navitoclax (ABT‑263) in triple‑negative breast cancer, lung adenocarcinoma and glioblastoma multiforme". International Journal of Oncology 60.1 (2022): 2.
Chicago
Lee, A., Jin, H., Masudul Haque, M., Kim, H. Y., Jung, H., Park, J. H., Kim, I., Song, J. Y., Yoon, H. K., Kim, H. K., Han, J., Park, I., Kim, K. S., Park, S. G."Synergism of a novel MCL‑1 downregulator, acriflavine, with navitoclax (ABT‑263) in triple‑negative breast cancer, lung adenocarcinoma and glioblastoma multiforme". International Journal of Oncology 60, no. 1 (2022): 2. https://doi.org/10.3892/ijo.2021.5292
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x
Spandidos Publications style
Lee A, Jin H, Masudul Haque M, Kim HY, Jung H, Park JH, Kim I, Song JY, Yoon HK, Kim HK, Kim HK, et al: Synergism of a novel MCL‑1 downregulator, acriflavine, with navitoclax (ABT‑263) in triple‑negative breast cancer, lung adenocarcinoma and glioblastoma multiforme. Int J Oncol 60: 2, 2022.
APA
Lee, A., Jin, H., Masudul Haque, M., Kim, H.Y., Jung, H., Park, J.H. ... Park, S.G. (2022). Synergism of a novel MCL‑1 downregulator, acriflavine, with navitoclax (ABT‑263) in triple‑negative breast cancer, lung adenocarcinoma and glioblastoma multiforme. International Journal of Oncology, 60, 2. https://doi.org/10.3892/ijo.2021.5292
MLA
Lee, A., Jin, H., Masudul Haque, M., Kim, H. Y., Jung, H., Park, J. H., Kim, I., Song, J. Y., Yoon, H. K., Kim, H. K., Han, J., Park, I., Kim, K. S., Park, S. G."Synergism of a novel MCL‑1 downregulator, acriflavine, with navitoclax (ABT‑263) in triple‑negative breast cancer, lung adenocarcinoma and glioblastoma multiforme". International Journal of Oncology 60.1 (2022): 2.
Chicago
Lee, A., Jin, H., Masudul Haque, M., Kim, H. Y., Jung, H., Park, J. H., Kim, I., Song, J. Y., Yoon, H. K., Kim, H. K., Han, J., Park, I., Kim, K. S., Park, S. G."Synergism of a novel MCL‑1 downregulator, acriflavine, with navitoclax (ABT‑263) in triple‑negative breast cancer, lung adenocarcinoma and glioblastoma multiforme". International Journal of Oncology 60, no. 1 (2022): 2. https://doi.org/10.3892/ijo.2021.5292
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