Eburicoic Acid, an Active Triterpenoid from the Fruiting Bodies of Basswood Cultivated Antrodia cinnamomea, Induces ER Stress-Mediated Autophagy in Human Hepatoma Cells

Su, Yu-Cheng; Liu, Chun‐Ting; Chu, Yung-Lin; Raghu, Rajasekaran; Kuo, Yueh‐Hsiung; Sheen, Lee‐Yan

doi:10.1016/s2225-4110(16)30117-1

Cited by 17 publications

(13 citation statements)

References 24 publications

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“…Apoptotic cell death was observed in colorectal, lung and liver cancer cells after A. cinnamomea treatment 10 , 17 , 42 , 45 . On the other hand, A. cinnamomea induced autophagic cell death in liver, pancreatic, head and neck cancer cells 41 , 46 , 47 . Our study identified that A. cinnamomea also induced autophagic cell death in colorectal cancer.…”

Section: Discussionmentioning

confidence: 97%

“…The numerous inducers of CHOP, such as DNA-alkylating agent methylmethane sulphate, tunicamycin, and thapsigargin, activated CHOP expression via the induction of ER stress 38 – 40 . A. cinnamomea reportedly induces ER stress-mediated apoptosis and autophagy in lung and liver cancer cells 41 , 42 . In our study, A. cinnamomea treatment induced CHOP-mediated autophagic cell death in colorectal cancer cells.…”

Section: Discussionmentioning

confidence: 99%

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Antrodia cinnamomea induces autophagic cell death via the CHOP/TRB3/Akt/mTOR pathway in colorectal cancer cells

Tsai

Chung²,

Lee

2018

Sci Rep

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Antrodia cinnamomea, a well-known traditional medicine used in Taiwan, is a potent anticancer drug for colorectal cancer, but the upstream molecular mechanism of its anticancer effects remains unclear. In this study, A. cinnamomea extracts showed cytotoxicity in HCT116, HT29, SW480, Caco-2 and, Colo205 colorectal cancer cells. Whole-genome expression profiling of A. cinnamomea extracts in HCT116 cells was performed. A. cinnamomea extracts upregulated the expression of the endoplasmic reticulum stress marker CHOP and its downstream gene TRB3. Moreover, dephosphorylation of Akt and mTOR as well as autophagic cell death were observed. Gene expression and autophagic cell death were reversed by the knockdown of CHOP and TRB3. Autophagy inhibition but not apoptosis inhibition reversed A. cinnamomea-induced cell death. Finally, we demonstrated that A. cinnamomea extracts significantly suppressed HCT116 tumour growth in nude mice. Our findings suggest that autophagic cell death via the CHOP/TRB3/Akt/mTOR pathway may represent a new mechanism of anti-colorectal cancer action by A. cinnamomea. A. cinnamomea is a new CHOP activator and potential drug that can be used in colorectal cancer treatment.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Antrodia cinnamomea induces autophagic cell death via the CHOP/TRB3/Akt/mTOR pathway in colorectal cancer cells

Tsai

Chung²,

Lee

2018

Sci Rep

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“…Su et al 37 have shown that eburicoic acid, a triterpenoid from A. cinnamomea, induced autophagy in human hepatoma Hep 3B cells of the ER stress pathway and increased the calcium ion concentration as well as the protein expressions of Bcl-2 and Beclin-1. This study reported that antcin K could cause ER stress in Hep 3B cells and also increase calcium ion concentration in the cytoplasm, which were consistent with the findings of the previous studies conducted in our laboratory.…”

Section: Discussionmentioning

confidence: 99%

Antcin K, an active triterpenoid from the fruiting bodies of basswood cultivated Antrodia cinnamomea, induces mitochondria and endoplasmic reticulum stress-mediated apoptosis in human hepatoma cells

Lai

Chu

et al. 2016

Journal of Traditional and Complementary Medicine

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Liver cancer is the second leading cause of cancer deaths in Taiwan as per the 2011 statistics and ranks fourth in cancer-related mortality in the world. Recent researches have shown that Antrodia cinnamomea, a Taiwan-specific medicinal mushroom, has biological activities, including hepatoprotection, anti-inflammation, antihepatitis B virus activity, and anticancer activity. In the present study, the antiproliferative activity and molecular mechanisms of antcin K, the most abundant ergostane triterpenoid from the fruiting bodies of basswood cultivated A. cinnamomea, were investigated using human hepatoma Hep 3B cells. The results showed that antcin K effectively reduced Hep 3B cells viability within 48 hours. Antcin K induced phosphatidylserine exposure, chromatin condensation, and DNA damage, but did not significantly increase autophagosome content or cause cell expansion and cell lysis. Thus, the principal mode of Hep 3B cells death induced by antcin K was apoptosis, rather than autophagy or necrosis. In-depth investigation of the molecular mechanisms revealed that antcin K first promoted reactive oxygen species generation and adenosine triphosphate depletion, leading to endoplasmic reticulum stress and resulting in mitochondrial membrane permeability changes. After losing the mitochondrial membrane potential, caspase-independent and caspase-dependent apoptosis-related proteins were released, including HtrA2, apoptotic-induced factor, endonuclease G, and cytochrome c. Cytochrome c activated caspase-9 and caspase-3, and cut downstream protein PARP, ultimately leading to cell apoptosis. These results suggested that antcin K induced mitochondrial and endoplasmic reticulum stress-mediated apoptosis in human hepatoma cells. Coupled with these findings, antcin K has a potential to be a complementary agent in liver cancer therapy.

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“…In previous studies, antcin K has been shown to exhibit antitumor effects against hepatoma and leukemia [ 12 , 29 , 44 ]. Antcin C, antcin B, and eburicoic acid also exhibit antitumor effects against hepatoma [ 31 , 45 , 46 ]. Dehydroeburicoic acid exhibits antitumor effects against the breast cancer T47D cell line [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Antrodia cinnamomea extract inhibits the proliferation of tamoxifen-resistant breast cancer cells through apoptosis and skp2/microRNAs pathway

Lin

Yang

et al. 2018

BMC Complement Altern Med

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BackgroundBreast cancer is the most common cancer in women and affects 1.38 million women worldwide per year. Antiestrogens such as tamoxifen, a selective estrogen receptor (ER) modulator, are widely used in clinics to treat ER-positive breast tumors. However, remissions of breast cancer are often followed by resistance to tamoxifen and disease relapse. Despite the increasing understanding of the resistance mechanisms, effective regimens for treating tamoxifen-resistant breast cancer are limited. Antrodia cinnamomea is a traditional medicinal mushroom native only to Taiwan. In this study, we aimed to examine in vitro effect of antrodia cinnamomea in the tamoxifen-resistant cancer.MethodsAntrodia cinnamomea was studied for its biological activity against proliferation of tamoxifen-resistant breast cancer by XTT assay. Next, the underlying mechanism was studied by flow cytometry, qPCR and Western’s blotting assay.ResultsOur results revealed that the ethanol extract of antrodia cinnamomea (AC) can inhibit the growth of breast cancer cells, including MCF-7 cell and tamoxifen-resistant MCF-7 cell lines. Combination treatment with AC and 10− 6 M tamoxifen have the better inhibitory effect on the proliferation of tamoxifen-resistant MCF-7 cells than only AC did. AC can induce apoptosis in these breast cancer cells. Moreover, it can suppress the mRNA expression of skp2 (S-phase kinase-associated protein 2) by increasing the expressions of miR-21-5p, miR-26-5p, and miR-30-5p in MCF-7 and tamoxifen-resistant MCF-7 cells.ConclusionsThese results suggest that the ethanol extract of antrodia cinnamomea could be a novel anticancer agent in the armamentarium of tamoxifen-resistant breast cancer management. Moreover, we hope to identify additional pure compounds that could serve as promising anti-breast cancer candidates for further clinical trials.

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Eburicoic Acid, an Active Triterpenoid from the Fruiting Bodies of Basswood Cultivated Antrodia cinnamomea, Induces ER Stress-Mediated Autophagy in Human Hepatoma Cells

Cited by 17 publications

References 24 publications

Antrodia cinnamomea induces autophagic cell death via the CHOP/TRB3/Akt/mTOR pathway in colorectal cancer cells

Antrodia cinnamomea induces autophagic cell death via the CHOP/TRB3/Akt/mTOR pathway in colorectal cancer cells

Antcin K, an active triterpenoid from the fruiting bodies of basswood cultivated Antrodia cinnamomea, induces mitochondria and endoplasmic reticulum stress-mediated apoptosis in human hepatoma cells

Antrodia cinnamomea extract inhibits the proliferation of tamoxifen-resistant breast cancer cells through apoptosis and skp2/microRNAs pathway

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