Manumycin A induces apoptosis in malignant pleural mesothelioma through regulation of Sp1 and activation of the mitochondria-related apoptotic pathway

  • Authors:
    • Ka Hwi Kim
    • Jung-Il Chae
    • Hana Oh
    • Jin Hyoung Cho
    • Ra-Ham Lee
    • Goo Yoon
    • Seung-Sik Cho
    • Young-Sik Cho
    • Mee-Hyun Lee
    • Kangdong Liu
    • Hyun-Jeong Lee
    • Jung-Hyun Shim
  • View Affiliations

  • Published online on: May 10, 2016     https://doi.org/10.3892/or.2016.4801
  • Pages: 117-124
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Abstract

Manumycin A (Manu A) is a natural product isolated from Streptomyces parvulus and has been reported to have anti-carcinogenic and anti-biotic properties. However, neither its molecular mechanism nor its molecular targets are well understood. Thus, the aim of the present study was to explore the possibility that Manu A has cancer preventive and chemotherapeutic effects on malignant pleural mesothelioma (MPM) through regulation of Sp1 and induction of mitochondrial cell death pathway. Manu A inhibited the cell viability of MSTO-211H and H28 cells in a concentration‑dependent manner as determined by MTS assay. IC50 values were calculated as 8.3 and 4.3 µM in the MSTO-311H and H28 cells following 48 h incubation, respectively. Manu A induced a significant increase in apoptotic indices as shown by DAPI staining, Annexin V assay, multi-caspase activity and mitochondrial membrane potential assay. The downregulation of Sp1 mRNA and protein expression by Manu A led to apoptosis by suppressing Sp1-regulated proteins (cyclin D1, Mcl-1 and survivin). Manu A decreased the protein levels of BID, Bcl-xL and PARP while it increased Bax levels. Manu A caused depolarization of the mitochondrial membrane with induction of CHOP, DR4 and DR5. Our results demonstrated that Manu A exerted anticancer effects by inducing apoptosis via inhibition of the Sp1-related signaling pathway in human MPM.
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July-2016
Volume 36 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kim KH, Chae J, Oh H, Cho JH, Lee R, Yoon G, Cho S, Cho Y, Lee M, Liu K, Liu K, et al: Manumycin A induces apoptosis in malignant pleural mesothelioma through regulation of Sp1 and activation of the mitochondria-related apoptotic pathway. Oncol Rep 36: 117-124, 2016
APA
Kim, K.H., Chae, J., Oh, H., Cho, J.H., Lee, R., Yoon, G. ... Shim, J. (2016). Manumycin A induces apoptosis in malignant pleural mesothelioma through regulation of Sp1 and activation of the mitochondria-related apoptotic pathway. Oncology Reports, 36, 117-124. https://doi.org/10.3892/or.2016.4801
MLA
Kim, K. H., Chae, J., Oh, H., Cho, J. H., Lee, R., Yoon, G., Cho, S., Cho, Y., Lee, M., Liu, K., Lee, H., Shim, J."Manumycin A induces apoptosis in malignant pleural mesothelioma through regulation of Sp1 and activation of the mitochondria-related apoptotic pathway". Oncology Reports 36.1 (2016): 117-124.
Chicago
Kim, K. H., Chae, J., Oh, H., Cho, J. H., Lee, R., Yoon, G., Cho, S., Cho, Y., Lee, M., Liu, K., Lee, H., Shim, J."Manumycin A induces apoptosis in malignant pleural mesothelioma through regulation of Sp1 and activation of the mitochondria-related apoptotic pathway". Oncology Reports 36, no. 1 (2016): 117-124. https://doi.org/10.3892/or.2016.4801