Recombinant Lz-8 from Ganoderma lucidum induces endoplasmic reticulum stress-mediated autophagic cell death in SGC-7901 human gastric cancer cells

Liang,Chongyang; Li,Hongrui; Zhou,Hui; Zhang,Shuqin; Liu,Zhiyi; Zhou,Qiuli; Sun,Fei

doi:10.3892/or.2011.1593

Recombinant Lz-8 from Ganoderma lucidum induces endoplasmic reticulum stress-mediated autophagic cell death in SGC-7901 human gastric cancer cells

Authors:
- Chongyang Liang
- Hongrui Li
- Hui Zhou
- Shuqin Zhang
- Zhiyi Liu
- Qiuli Zhou
- Fei Sun
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Affiliations: Institute of Frontier Medical Science of Jilin University, Changchun 130021, P.R. China, Institute of Frontier Medical Science of Jilin University, 1163 Xinmin Street, Changchun 130021, P.R. China
Published online on: December 14, 2011 https://doi.org/10.3892/or.2011.1593
Pages: 1079-1089

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Abstract

In Asia, the mushroom of the fungus Ganoderma lucidum has been widely used as a traditional medicine for the past two millennia. The aim of this study was to investigate the anticancer activity of recombinant Lz-8 (rLz-8), a protein belonging to a family of fungal immunomodulatory proteins. We report that rLz-8 induces endoplasmic reticulum (ER) stress-mediated autophagic cell death in the human gastric cancer cell line SGC-7901. Our results show that rLz-8 induces autophagic cell death by aggregating in the ER, triggering ER stress and the ATF4-CHOP pathway. A foreign protein, in the ER rLz-8 causes the activation of the ubiquitine/proteasome ER-associated degradation (ERAD) system. The autophagic arm of this system is then overstimulated by an excessive abundance of rLz-8 and causes the cell’s death through an over-autophagic response. We also found that caspase inhibitors do not prevent rLz-8-induced cell death, and therefore the autophagic response induced by rLz-8 is independent of caspase activation.

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