Multiple antitumor effects of picropodophyllin in colon carcinoma cell lines: Clinical implications

  • Authors:
    • Xiaoying Feng
    • Eiman Aleem
    • Yingbo Lin
    • Magnus Axelson
    • Olle Larsson
    • Thomas Strömberg
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  • Published online on: December 6, 2011     https://doi.org/10.3892/ijo.2011.1281
  • Pages: 1251-1258
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Abstract

Although colorectal cancer can be successfully treated by conventional strategies such as chemo/radiotherapy and surgery, a substantial number of cases, in particular those with liver metastases, remain incurable. Therefore, novel treatment approaches are warranted. The IGF-1R and its ligands, mainly IGF-1 and IGF-2, have been suggested to play pivotal roles in proliferation, survival and migration of adenocarcinoma cells of the colon/rectum. Therefore, interference with IGF-1R-mediated signaling may represent a therapeutic option for this malignancy. In this study, semi-quantitative RT-PCR analyses of 48 paired, colorectal cancer patient samples showed significant overexpression of tumor IGF-1R and IGF-2 mRNA. There was also an overexpression of MMP-7, which was significantly correlated with histopathological parameters. Based on these findings, the effect of the IGF-1R-inhibitory cyclolignan picropodophyllin (PPP) was assessed in the four colon carcinoma cell lines HT-29, HCT-116, DLD-1 and CaCO-2. PPP strongly and dose-dependently inhibited proliferation and migration in all cell lines. However, when exposed to 0.5 µM PPP, only HT-29 showed a net decrease of viable cells as compared with the cell number at the beginning of the experiment, a finding that coincided with decreased expression/phosphorylation of IGF-1R, AKT and ERK. This cell line also exhibited PPP-induced downregulation of MMP-7 and MMP-9. Similar to the DLD-1 and HCT-116 cell lines, HT-29 also showed substantial cell detachment in response to PPP. Although a net reduction of cells by PPP seems to require a synchronized downregulation of IGF-1R, AKT and ERK1/2, part of the antitumor effect may be explained by other, possibly IGF-1R-unrelated mechanism(s). Such a multitude of inhibitory effects of PPP in colon cancer cells together with its low toxicity in vivo makes it a promising drug candidate in the treatment of this disease.
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April 2012
Volume 40 Issue 4

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Spandidos Publications style
Feng X, Aleem E, Lin Y, Axelson M, Larsson O and Strömberg T: Multiple antitumor effects of picropodophyllin in colon carcinoma cell lines: Clinical implications. Int J Oncol 40: 1251-1258, 2012
APA
Feng, X., Aleem, E., Lin, Y., Axelson, M., Larsson, O., & Strömberg, T. (2012). Multiple antitumor effects of picropodophyllin in colon carcinoma cell lines: Clinical implications. International Journal of Oncology, 40, 1251-1258. https://doi.org/10.3892/ijo.2011.1281
MLA
Feng, X., Aleem, E., Lin, Y., Axelson, M., Larsson, O., Strömberg, T."Multiple antitumor effects of picropodophyllin in colon carcinoma cell lines: Clinical implications". International Journal of Oncology 40.4 (2012): 1251-1258.
Chicago
Feng, X., Aleem, E., Lin, Y., Axelson, M., Larsson, O., Strömberg, T."Multiple antitumor effects of picropodophyllin in colon carcinoma cell lines: Clinical implications". International Journal of Oncology 40, no. 4 (2012): 1251-1258. https://doi.org/10.3892/ijo.2011.1281