Cystatin SN inhibits auranofin-induced cell death by autophagic induction and ROS regulation via glutathione reductase activity in colorectal cancer

Cited 26 time in scopus
Metadata Downloads

Full metadata record

DC FieldValueLanguage
dc.contributor.authorByung Moo Oh-
dc.contributor.authorSeon-Jin Lee-
dc.contributor.authorHee Jun Cho-
dc.contributor.authorYun Sun Park-
dc.contributor.authorJong-Tae Kim-
dc.contributor.authorSuk Ran Yoon-
dc.contributor.authorSang Chul Lee-
dc.contributor.authorJ S Lim-
dc.contributor.authorBo Yeon Kim-
dc.contributor.authorYong Kyung Choe-
dc.contributor.authorHee Gu Lee-
dc.description.abstractCystatin SN (CST1) is a specific inhibitor belonging to the cystatin superfamily that controls the proteolytic activities of cysteine proteases such as cathepsins. Our previous study showed that high CST1 expression enhances tumor metastasis and invasiveness in colorectal cancer. Recently, auranofin (AF), a gold(I)-containing thioredoxin reductase 1 (TrxR1) inhibitor, has been used clinically to treat rheumatoid arthritis. AF is a proteasome-associated deubiquitinase inhibitor and can act as an anti-tumor agent. In this study, we investigated whether CST1 expression induces autophagy and tumor cell survival. We also investigated the therapeutic effects of AF as an anti-tumor agent in colorectal cancer (CRC) cells. We found that CRC cells expressing high levels of CST1 undergo increased autophagy and exhibit chemotherapeutic resistance to AF-induced cell death, while those expressing low levels of CST1 are sensitive to AF. We also observed that knockdown of CST1 in high-CST1 CRC cells using CST1-specific small interfering RNAs attenuated autophagic activation and restored AF-induced cell mortality. Conversely, the overexpression of CST1 increased autophagy and viability in cells expressing low levels of CST1. Interestingly, high expression of CST1 attenuates AF-induced cell death by inhibiting intracellular reactive oxygen species (ROS) generation, as demonstrated by the fact that the blockage of ROS production reversed AF-induced cell death in CRC cells. In addition, upregulation of CST1 expression increased cellular glutathione reductase (GR) activity, reducing the cellular redox state and inducing autophagy in AF-treated CRC cells. These results suggest that high CST1 expression may be involved in autophagic induction and protects from AF-induced cell death by inhibition of ROS generation through the regulation of GR activity. ⓒ The Author(s) 2017.-
dc.publisherSpringer-Nature Pub Group-
dc.titleCystatin SN inhibits auranofin-induced cell death by autophagic induction and ROS regulation via glutathione reductase activity in colorectal cancer-
dc.title.alternativeCystatin SN inhibits auranofin-induced cell death by autophagic induction and ROS regulation via glutathione reductase activity in colorectal cancer-
dc.citation.titleCell Death & Disease-
dc.contributor.affiliatedAuthorByung Moo Oh-
dc.contributor.affiliatedAuthorSeon-Jin Lee-
dc.contributor.affiliatedAuthorHee Jun Cho-
dc.contributor.affiliatedAuthorYun Sun Park-
dc.contributor.affiliatedAuthorJong-Tae Kim-
dc.contributor.affiliatedAuthorSuk Ran Yoon-
dc.contributor.affiliatedAuthorSang Chul Lee-
dc.contributor.affiliatedAuthorBo Yeon Kim-
dc.contributor.affiliatedAuthorYong Kyung Choe-
dc.contributor.affiliatedAuthorHee Gu Lee-
dc.identifier.bibliographicCitationCell Death & Disease, vol. 8, no. 3, pp. e2682-e2682-
Appears in Collections:
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.

Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.