Journal of Microbiology and Biotechnology
The Korean Society for Microbiology and Biotechnology publishes the Journal of Microbiology and Biotechnology.

2019 ; Vol.29-4: 571~576

AuthorSae-Bom Yoon, Hae-Ryong Park
Place of dutyKyungnam University, Republic of Korea
TitleArctigenin Inhibits Etoposide Resistance in HT-29 Colon Cancer Cells during Microenvironmental Stress
PublicationInfo J. Microbiol. Biotechnol.2019 ; Vol.29-4
AbstractMicroenvironmental stress, which is naturally observed in solid tumors, has been implicated in anticancer drug resistance. This tumor-specific stress causes the degradation of topoisomerase IIα, rendering cells resistant to topoisomerase IIα-targeted anticancer agents. In addition, microenvironmental stress can induce the overexpression of 78kDa glucose regulated protein (GRP78), which can subsequently block the activation of apoptosis induced by treatment with anticancer agents. Therefore, inhibition of topoisomerase IIα degradation and reduction in GRP78 expression may be effective strategies for inhibiting anticancer drug resistance. In this study, we investigated the active compound arctigenin, which inhibited microenvironmental stress-induced etoposide resistance in HT-29 cells. Arctigenin was also highly toxic to etoposide-resistant HT-29 cells, with an IC50 value of 10 μM for colony formation. We further showed that arctigenin inhibited the degradation of topoisomerase IIα and reduced the expression of GRP78. Thus, these results suggest that arctigenin is a novel therapeutic agent that inhibits resistance to etoposide associated with microenvironmental stress conditions.
Full-Text
Key_wordAnticancer resistance, microenvironmental stress, topoisomerase-IIα, GRP78, arctigenin
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