Publication:
Inostamycin enhanced TRAIL-induced apoptosis through DR5 upregulation on the cell surface

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Issued Date

2012

Resource Type

Article

File Type

application/pdf

ISSN

218820

DOI

10.1038/ja.2012.21

Other identifier(s)

2-s2.0-84863332135

Rights Holder(s)

Scopus

Bibliographic Citation

Journal of Antibiotics. Vol 65, No.6 (2012), p.295-300

Suggested Citation

Yamamoto K., Makino M., Watanapokasin R., Tashiro E., Imoto M. Inostamycin enhanced TRAIL-induced apoptosis through DR5 upregulation on the cell surface. Journal of Antibiotics. Vol 65, No.6 (2012), p.295-300. doi:10.1038/ja.2012.21 Retrieved from: https://hdl.handle.net/20.500.14740/7043

Title

Inostamycin enhanced TRAIL-induced apoptosis through DR5 upregulation on the cell surface

Author(s)

Yamamoto K.
 Makino M.
 Watanapokasin R.
 Tashiro E.
 Imoto M.

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been considered as a possible therapeutic agent for cancer treatment. This is because of its selective cytotoxicity against various cancer cells without a detrimental effect on normal cells. However, recent studies have reported that the potential application of TRAIL in cancer therapy is limited, as many cancer cells have been found to be resistant to TRAIL. Therefore, small molecule compounds that potentiate the cytotoxicity of TRAIL would be strategic candidates for therapeutic applications in combination with TRAIL. Here we found that a combined treatment of inostamycin and TRAIL synergistically induced caspase-dependent apoptosis in HCT116 cells. Inostamycin upregulated DR5, and a knockdown of DR5 suppressed the apoptosis that was synergistically induced by co-treatment with inostamycin and TRAIL. Moreover, inostamycin increased the expression of DR5 on the cell surface. Therefore, inostamycin-increased cell surface expression of DR5 may have contributed to the enhancement of TRAIL-induced apoptosis. Our study suggests that combined treatment with inostamycin and TRAIL may offer a strategy to overcome TRAIL resistance in tumor cells. © 2012 Japan Antibiotics Research Association All rights reserved.

Subject(s)

Caspase
 Death receptor 4
 Death receptor 5
 Inostamycin
 Small interfering RNA
 Tumor necrosis factor related apoptosis inducing ligand
 Apoptosis
 Article
 Cancer cell
 Cell surface
 Colorectal cancer
 Controlled study
 Drug potentiation
 Human
 Human cell
 Priority journal
 Upregulation
 Antineoplastic Combined Chemotherapy Protocols
 Apoptosis
 Blotting, Western
 Cell Survival
 Colorectal Neoplasms
 Drug Synergism
 Flow Cytometry
 Furans
 Gene Expression Regulation, Neoplastic
 HCT116 Cells
 Humans
 Real-Time Polymerase Chain Reaction
 Receptors, TNF-Related Apoptosis-Inducing Ligand
 RNA, Neoplasm
 RNA, Small Interfering
 TNF-Related Apoptosis-Inducing Ligand
 Up-Regulation

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URI

https://hdl.handle.net/20.500.14740/7043

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Scopus: Year 1983-2021

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