2019 ; Vol.29-4: 571~576
|Author||Sae-Bom Yoon, Hae-Ryong Park|
|Place of duty||Kyungnam University, Republic of Korea|
|Title||Arctigenin Inhibits Etoposide Resistance in HT-29 Colon Cancer Cells during Microenvironmental Stress|
J. Microbiol. Biotechnol.2019 ;
|Abstract||Microenvironmental 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
|Key_word||Anticancer resistance, microenvironmental stress, topoisomerase-IIα, GRP78, arctigenin|
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