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KMID : 1161520220260010028
Animal Cells and Systems
2022 Volume.26 No. 1 p.28 ~ p.36
Kazinol C from Broussonetia kazinoki stimulates autophagy via endoplasmic reticulum stress-mediated signaling
Lee Yun-Kyeong

Kwon Jun-Hee
Jeong Ji-Hye
Ryu Jae-Ha
Kim Keun-Il
Abstract
Autophagy modulators are considered putative therapeutic targets because of the role of autophagy in cancer progression. Kazinol C, a 1,3-diphenylpropane from the plant Broussonetia kazinoki, has been shown to induce apoptosis in colon cancer cells through the activation of AMPK at high concentrations. In the present study, we found that Kazinol C induced autophagy through endoplasmic reticulum stress-mediated unfolded protein response signaling in several normal and cancer cell lines at low concentrations of Kazinol C that did not induce apoptosis. Kazinol C activated the transducers of unfolded protein response signaling, leading to target gene expression, LC3-II conversion, and TFEB nuclear translocation. Chemical inhibition of endoplasmic reticulum stress reduced LC3-II conversion. In addition, blockade of autophagy by knockout of Atg5 or treatment with 3-MA enhanced Kazinol C-induced apoptosis. In summary, we have uncovered Kazinol C as a novel autophagy inducer and confirmed the role of autophagy as a cellular stress protector.
KEYWORD
Kazinol C, endoplasmic reticulum stress, unfolded protein response, autophagy, apoptosis
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