Survivin may be a Key Target for Oxaliplatin

Moo Jun Baek

doi:10.3393/jksc.2010.26.4.239

Articles

Page Path: HOME > J Korean Soc Coloproctol > Volume 26(4); 2010 > Article

Editorial Survivin may be a Key Target for Oxaliplatin: Moo Jun Baek; Journal of the Korean Society of Coloproctology 2010;26(4):239-239.
DOI: https://doi.org/10.3393/jksc.2010.26.4.239
Published online: August 31, 2010

Department of Surgery, Soonchunhyang University College of Medicine, Cheonan, Korea.

Correspondence to: Moo Jun Baek, M.D. Department of Surgery, Soonchunhyang University College of Medicine, 23-20 Bongmyeong-dong, Dongnam-gu, Cheonan 330-721, Korea. Tel: +82-41-570-3633, Fax: +82-41-571-0129, ssurge@sch.ac.kr

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

2,980 Views
30 Download
1 Crossref
2 Scopus

Full Article

Download PDF

REFERENCES

See Article on Page [Related article:] 246-253

Oxaliplatin, a third-generation platinum-derived chemotherapeutic agent, displays a wide spectrum of antitumor activity [1]. Similar to other platinum drugs, its biological activity is due to its ability to form lethal DNA lesions, including interstrand DNA crosslinks and DNA-protein crosslinks [2]. Oxaliplatin has fewer side-effects compared to other platinum drugs in terms of nephrotoxicity and myelosuppression [3]. Clinically, oxaliplatin effectively treats colorectal cancer in combination with fluorouracil and leucovorin [4]. However, the underlying molecular responses to oxaliplatin in colorectal cancer remain largely unknown.

In the present study, the authors investigated the effect of oxaliplatin on one colon cancer cell line, HCT 119. They demonstrated that oxaliplatin treatment inhibited the expression of the survivin protein and survivin mRNA in HCT116 colon cancer cells. The authors report that the expression of the survivin-2B variants, which have no antiapoptotic activity but control the cell mitosis by localization on a microtubule, was reduced continuously over the first two days following treatment with oxaliplatin. In immunocytochemistry, expression of survivin in the cytoplasm was reduced and, in particular, survivan was not expressed in microtubules and contractile rings.

The authors conjecture that the reason for the continuous decrease of survivin-2B, which is known to have little apoptosis inhibition effect among the survivin variants, might have been that survivin-2B failed to be positioned normally in the microtubule during the G2/M phase of cell cycle, thereby hindering the formation of a bipolar spindle during mitosis and, consequently, causing a mitotic catastrophe. According to the results of the authors' research, one of the working mechanisms of oxaliplatin may be that it not only causes apoptosis by inhibiting the expression of survivin but also impedes the formation of a bipolar spindle during mitosis as survivin fails to be positioned normally in the microtubule because it is not expressed properly in the microtubule or the contractile ring when the cells have reached the interphase of the cell cycle.

The authors' study is considered meaningful in that it contributes to an explanation of the molecular effect of oxaliplatin, which is used most commonly in chemotherapy for colon cancer. These data indicate that survivin may be a key target for oxaliplatin. The ability of oxaliplatin to induce different modes of cell death may contribute to its efficacy in treating colorectal cancer.

REFERENCES

1. Rixe O, Ortuzar W, Alvarez M, Parker R, Reed E, Paull K, et al. Oxaliplatin, tetraplatin, cisplatin, and carboplatin: spectrum of activity in drug-resistant cell lines and in the cell lines of the National Cancer Institute's Anticancer Drug Screen panel. Biochem Pharmacol 1996;52:1855–1865. Article PubMed
2. Woynarowski JM, Faivre S, Herzig MC, Arnett B, Chapman WG, Trevino AV, et al. Oxaliplatin-induced damage of cellular DNA. Mol Pharmacol 2000;58:920–927. Article PubMed
3. Misset JL, Bleiberg H, Sutherland W, Bekradda M, Cvitkovic E. Oxaliplatin clinical activity: a review. Crit Rev Oncol Hematol 2000;35:75–93. Article PubMed
4. Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004;22:23–30. Article PubMed

Figure & Data

References

Citations

Citations to this article as recorded by

A role for ceramide glycosylation in resistance to oxaliplatin in colorectal cancer
James P. Madigan, Robert W. Robey, Joanna E. Poprawski, Huakang Huang, Christopher J. Clarke, Michael M. Gottesman, Myles C. Cabot, Daniel W. Rosenberg
Experimental Cell Research.2020; 388(2): 111860. CrossRef

Cite this Article

Cite this Article: export Copy Download Format; Close

Download Citation

Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

Format:

RIS — For EndNote, ProCite, RefWorks, and most other reference management software
BibTeX — For JabRef, BibDesk, and other BibTeX-specific software

Include:

Citation for the content below
Citation and abstract for the content below

Survivin may be a Key Target for Oxaliplatin

J Korean Soc Coloproctol. 2010;26(4):239-239. Published online August 31, 2010

DOI: https://doi.org/10.3393/jksc.2010.26.4.239

XML Download

Survivin may be a Key Target for Oxaliplatin