Therapeutic molecular targeting of 15-lipoxygenase-1 in colon cancer

Yuanqing Wu; Bingliang Fang; Xiulan Q. Yang; Li Wang; Dongning Chen; Victor Krasnykh; Bing Z. Carter; Jeffrey S. Morris; Imad Shureiqi

doi:10.1038/mt.2008.44

Therapeutic molecular targeting of 15-lipoxygenase-1 in colon cancer

Yuanqing Wu, Bingliang Fang, Xiulan Q. Yang, Li Wang, Dongning Chen, Victor Krasnykh, Bing Z. Carter, Jeffrey S. Morris, Imad Shureiqi

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

Molecular targeting for apoptosis induction is being developed for better treatment of cancer. Downregulation of 15-lipoxygenase-1 (15-LOX-1) is linked to colorectal tumorigenesis. Re-expression of 15-LOX-1 in cancer cells by pharmaceutical agents induces apoptosis. Antitumorigenic agents can also induce apoptosis via other molecular targets. Whether restoring 15-LOX-1 expression in cancer cells is therapeutically sufficient to inhibit colonic tumorigenesis remains unknown. We tested this question using an adenoviral delivery system to express 15-LOX-1 in in vitro and in vivo models of colon cancer. We found that (i) the adenoviral vector 5/3 fiber modification enhanced 15-LOX-1 gene transduction in various colorectal cancer cell lines, (ii) the adenoviral vector delivery restored 15-LOX-1 expression and enzymatic activity to therapeutic levels in colon cancer cell lines, and (iii) 15-LOX-1 expression downregulated the expression of the antiapoptotic proteins X-linked inhibitor of apoptosis protein (XIAP) and BcL-XL, activated caspase-3, triggered apoptosis, and inhibited cancer cell survival in vitro and the growth of colon cancer xenografts in vivo. Thus, selective molecular targeting of 15-LOX-1 expression is sufficient to re-establish apoptosis in colon cancer cells and inhibit tumorigenesis. These data provide the rationale for further development of therapeutic strategies to target 15-LOX-1 molecularly for treating colonic tumorigenesis.

Original language	English (US)
Pages (from-to)	886-892
Number of pages	7
Journal	Molecular Therapy
Volume	16
Issue number	5
DOIs	https://doi.org/10.1038/mt.2008.44
State	Published - May 2008

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics
Pharmacology
Drug Discovery

Access to Document

10.1038/mt.2008.44

Cite this

@article{9b496fb9da59407cbb7ac922d961b3e2,

title = "Therapeutic molecular targeting of 15-lipoxygenase-1 in colon cancer",

abstract = "Molecular targeting for apoptosis induction is being developed for better treatment of cancer. Downregulation of 15-lipoxygenase-1 (15-LOX-1) is linked to colorectal tumorigenesis. Re-expression of 15-LOX-1 in cancer cells by pharmaceutical agents induces apoptosis. Antitumorigenic agents can also induce apoptosis via other molecular targets. Whether restoring 15-LOX-1 expression in cancer cells is therapeutically sufficient to inhibit colonic tumorigenesis remains unknown. We tested this question using an adenoviral delivery system to express 15-LOX-1 in in vitro and in vivo models of colon cancer. We found that (i) the adenoviral vector 5/3 fiber modification enhanced 15-LOX-1 gene transduction in various colorectal cancer cell lines, (ii) the adenoviral vector delivery restored 15-LOX-1 expression and enzymatic activity to therapeutic levels in colon cancer cell lines, and (iii) 15-LOX-1 expression downregulated the expression of the antiapoptotic proteins X-linked inhibitor of apoptosis protein (XIAP) and BcL-XL, activated caspase-3, triggered apoptosis, and inhibited cancer cell survival in vitro and the growth of colon cancer xenografts in vivo. Thus, selective molecular targeting of 15-LOX-1 expression is sufficient to re-establish apoptosis in colon cancer cells and inhibit tumorigenesis. These data provide the rationale for further development of therapeutic strategies to target 15-LOX-1 molecularly for treating colonic tumorigenesis.",

author = "Yuanqing Wu and Bingliang Fang and Yang, {Xiulan Q.} and Li Wang and Dongning Chen and Victor Krasnykh and Carter, {Bing Z.} and Morris, {Jeffrey S.} and Imad Shureiqi",

note = "Funding Information: We are in debt to L. Clifton Stephens, Section of Veterinary Pathology, The University of Texas M. D. Anderson Cancer Center, for performing necropsies and histological examinations of nude mice. We also thank Karen Phillips from the Department of Scientific Publications at The University of Texas M. D. Anderson Cancer Center for editing this manuscript. In addition, we acknowledge the assistance from Sijin Wen, Department of Biostatistics and Applied Mathematics, The University of Texas M. D. Anderson Cancer Center, in performing the statistical analyses. Imad Shureiqi was supported by the National Cancer Institute, NIH, Department of Health and Human Services R01 grant CA104278; by the American Cancer Society Research Scholar Award RSG-04-020-01-CNE; by the Caroline Wiess Law Endowment for Cancer Prevention; and by the National Colorectal Cancer Research Alliance. No author has any financial or other interests with regard to this manuscript that might be construed as a conflict of interest.",

year = "2008",

month = may,

doi = "10.1038/mt.2008.44",

language = "English (US)",

volume = "16",

pages = "886--892",

journal = "Molecular Therapy",

issn = "1525-0016",

publisher = "Nature Publishing Group",

number = "5",

}

TY - JOUR

T1 - Therapeutic molecular targeting of 15-lipoxygenase-1 in colon cancer

AU - Wu, Yuanqing

AU - Fang, Bingliang

AU - Yang, Xiulan Q.

AU - Wang, Li

AU - Chen, Dongning

AU - Krasnykh, Victor

AU - Carter, Bing Z.

AU - Morris, Jeffrey S.

AU - Shureiqi, Imad

N1 - Funding Information: We are in debt to L. Clifton Stephens, Section of Veterinary Pathology, The University of Texas M. D. Anderson Cancer Center, for performing necropsies and histological examinations of nude mice. We also thank Karen Phillips from the Department of Scientific Publications at The University of Texas M. D. Anderson Cancer Center for editing this manuscript. In addition, we acknowledge the assistance from Sijin Wen, Department of Biostatistics and Applied Mathematics, The University of Texas M. D. Anderson Cancer Center, in performing the statistical analyses. Imad Shureiqi was supported by the National Cancer Institute, NIH, Department of Health and Human Services R01 grant CA104278; by the American Cancer Society Research Scholar Award RSG-04-020-01-CNE; by the Caroline Wiess Law Endowment for Cancer Prevention; and by the National Colorectal Cancer Research Alliance. No author has any financial or other interests with regard to this manuscript that might be construed as a conflict of interest.

PY - 2008/5

Y1 - 2008/5

N2 - Molecular targeting for apoptosis induction is being developed for better treatment of cancer. Downregulation of 15-lipoxygenase-1 (15-LOX-1) is linked to colorectal tumorigenesis. Re-expression of 15-LOX-1 in cancer cells by pharmaceutical agents induces apoptosis. Antitumorigenic agents can also induce apoptosis via other molecular targets. Whether restoring 15-LOX-1 expression in cancer cells is therapeutically sufficient to inhibit colonic tumorigenesis remains unknown. We tested this question using an adenoviral delivery system to express 15-LOX-1 in in vitro and in vivo models of colon cancer. We found that (i) the adenoviral vector 5/3 fiber modification enhanced 15-LOX-1 gene transduction in various colorectal cancer cell lines, (ii) the adenoviral vector delivery restored 15-LOX-1 expression and enzymatic activity to therapeutic levels in colon cancer cell lines, and (iii) 15-LOX-1 expression downregulated the expression of the antiapoptotic proteins X-linked inhibitor of apoptosis protein (XIAP) and BcL-XL, activated caspase-3, triggered apoptosis, and inhibited cancer cell survival in vitro and the growth of colon cancer xenografts in vivo. Thus, selective molecular targeting of 15-LOX-1 expression is sufficient to re-establish apoptosis in colon cancer cells and inhibit tumorigenesis. These data provide the rationale for further development of therapeutic strategies to target 15-LOX-1 molecularly for treating colonic tumorigenesis.

AB - Molecular targeting for apoptosis induction is being developed for better treatment of cancer. Downregulation of 15-lipoxygenase-1 (15-LOX-1) is linked to colorectal tumorigenesis. Re-expression of 15-LOX-1 in cancer cells by pharmaceutical agents induces apoptosis. Antitumorigenic agents can also induce apoptosis via other molecular targets. Whether restoring 15-LOX-1 expression in cancer cells is therapeutically sufficient to inhibit colonic tumorigenesis remains unknown. We tested this question using an adenoviral delivery system to express 15-LOX-1 in in vitro and in vivo models of colon cancer. We found that (i) the adenoviral vector 5/3 fiber modification enhanced 15-LOX-1 gene transduction in various colorectal cancer cell lines, (ii) the adenoviral vector delivery restored 15-LOX-1 expression and enzymatic activity to therapeutic levels in colon cancer cell lines, and (iii) 15-LOX-1 expression downregulated the expression of the antiapoptotic proteins X-linked inhibitor of apoptosis protein (XIAP) and BcL-XL, activated caspase-3, triggered apoptosis, and inhibited cancer cell survival in vitro and the growth of colon cancer xenografts in vivo. Thus, selective molecular targeting of 15-LOX-1 expression is sufficient to re-establish apoptosis in colon cancer cells and inhibit tumorigenesis. These data provide the rationale for further development of therapeutic strategies to target 15-LOX-1 molecularly for treating colonic tumorigenesis.

UR - http://www.scopus.com/inward/record.url?scp=42549159861&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42549159861&partnerID=8YFLogxK

U2 - 10.1038/mt.2008.44

DO - 10.1038/mt.2008.44

M3 - Article

C2 - 18388920

AN - SCOPUS:42549159861

SN - 1525-0016

VL - 16

SP - 886

EP - 892

JO - Molecular Therapy

JF - Molecular Therapy

IS - 5

ER -

Therapeutic molecular targeting of 15-lipoxygenase-1 in colon cancer

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this