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A specific cell-penetrating peptide induces apoptosis in SKOV3 cells by down-regulation of Bcl-2

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Abstract

Peptides are emerging as pharmaceutical agents in cancer therapy. The peptide, TLSGAFELSRDK (TLS) is a targeting ligand that can specifically triggers cellular uptake by binding to SKOV3 cells. Cell surface proteins and the C-terminal basic residues of the TLS are required for effective cell penetration, and the uptake process is energy-dependent. It inhibited the proliferation of SKOV3 cells and induced early-stage apoptosis by down-regulation of Bcl-2 expression mediated through a caspase-dependent pathway. The synergistic anti-proliferative effects of the peptide TLS and doxorubicin on SKOV3 cells were further investigated. Taken together, TLS, acting as a combination of a targeted ligand and a therapeutic agent, was a promising candidate for the development of peptide-based therapies in ovarian cancer.

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References

  • Bélanger S, Côté M, Lane D, L’Espérance S, Rancourt C, Piché A (2005) Bcl-2 decreases cell proliferation and promotes accumulation of cells in S phase without affecting the rate of apoptosis in human ovarian carcinoma cells. Gynecol Oncol 97:796–806

    Article  PubMed  Google Scholar 

  • Bhutia SK, Maiti TK (2008) Targeting tumors with peptides from natural sources. Trend Biotechnol 26:210–217

    Article  CAS  Google Scholar 

  • Bogdanowich-Knipp SJ, Chakrabarti S, Siahaan TJ (1999) Solution stability of linear vs. cyclic RGD peptides. J Pept Res 53:530–541

    Article  PubMed  CAS  Google Scholar 

  • Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516

    Article  PubMed  CAS  Google Scholar 

  • Futaki S, Nakase I, Tadokoro A, Takeuchi T, Jones AT (2007) Arginine-rich peptides and their internalization mechanisms. Biochem Soc Trans 35:784–787

    Article  PubMed  CAS  Google Scholar 

  • Gewirtz DA (1999) A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol 57:727–741

    Article  PubMed  CAS  Google Scholar 

  • Hedman H, Nilsson J, Guo D, Henriksson R (2002) Is LRIG1 a tumour suppressor gene at chromosome 3p14.3? Acta Oncol 41:352–354

    Article  PubMed  CAS  Google Scholar 

  • Kolonin MG, Bover L, Sun J, Zurita AJ, Do KA, Lahdenranta J et al (2006) Ligand-directed surface profiling of human cancer cells with combinatorial peptide libraries. Cancer Res 66:34–40

    Article  PubMed  CAS  Google Scholar 

  • Laakkonen P, Åkerman ME, Biliran H et al (2004) Antitumor activity of a homing peptide that targets tumor lymphatics and tumor cells. Proc Natl Acad Sci USA 101:9381–9386

    Article  PubMed  CAS  Google Scholar 

  • Liu B, Chen Q, Tian D, Wu L, Wang J, Cai Q (2011) Increased leucine-rich repeats and immunoglobulin-like domains 1 expression enhances chemosensitivity in glioma. Neural Regen Res 6:2516–2520

    CAS  Google Scholar 

  • Lock RB, Stribinskiene L (1996) Dual modes of death induced by etoposide in human epithelial tumor cells allow Bcl-2 to inhibit apoptosis without affecting clonogenic survival. Cancer Res 56:4006–4012

    PubMed  CAS  Google Scholar 

  • Manion MK, Hockenbery DM (2003) Targeting BCL-2-related proteins in cancer therapy. Cancer Biol Ther 2:105–114

    Google Scholar 

  • Nishimura S, Takahashi S, Kamikatahira H, Kuroki Y, Jaalouk DE et al (2008) Combinatorial targeting of the macropinocytotic pathway in leukemia and lymphoma cells. J Biol Chem 283:11752–11762

    Article  PubMed  CAS  Google Scholar 

  • Sugahara KN, Teesalu T, Karmali PP, Kotamraju VR, Agemy L, Girard OM et al (2009) Tissue-penetrating delivery of compounds and nanoparticles into tumors. Cell 16:510–520

    CAS  Google Scholar 

  • Teesalu T, Sugahara KN, Kotamraju VR, Ruoslahti E (2009) C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration. Proc Natl Acad Sci USA 106:16157–16162

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work has been supported by the National Natural Science Foundation of China (Project Nos. 51173120, 51273122 and 51202151). The supports of Sichuan Province through two Key Technologies Research and Development Programs of Sichuan Province (2010SZ0088 & 2008SZ0021) are also acknowledged with gratitude.

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No potential conflict of interest was disclosed.

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Correspondence to Guangfu Yin.

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Ma, C., Yin, G., You, F. et al. A specific cell-penetrating peptide induces apoptosis in SKOV3 cells by down-regulation of Bcl-2. Biotechnol Lett 35, 1791–1797 (2013). https://doi.org/10.1007/s10529-013-1263-x

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  • DOI: https://doi.org/10.1007/s10529-013-1263-x

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