Medicinal Fungus<i>Antrodia cinnamomea</i>Inhibits Growth and Cancer Stem Cell Characteristics of Hepatocellular Carcinoma

Liu, Yu Ming; Liu, Yu Kuo; Lan, Keng Li; Lee, Yu Wei; Tsai, Tung Hu; Chen, Yu-Jen

doi:10.1155/2013/569737

Cited by 13 publications

(13 citation statements)

References 25 publications

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“…Antrodia cinnamomea , a Taiwan-specific mushroom, has been reported to have numerous biological activities including hepatoprotection, anti-inflammation, 1 antihepatitis C virus activity, 2 and anticancer activity. 3 Liver cancer ranks fourth in cancer-related mortality around the world (WHO 2008) and is the second leading cause of cancer deaths in Taiwan. Twenty years ago, the major cause of liver cancer in Taiwan was hepatitis virus infection, such as hepatitis B virus (HBV) infection.…”

Section: Introductionmentioning

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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Section: Introductionmentioning

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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“…AC was also reported able to protect liver cells from free radical-induced oxidative stresses through the Nrf-2 activation and up-regulation of the MAP kinase-mediated antioxidant genes [ 26 , 27 ]. Moreover, AC was reported able to inhibit proliferation of head and neck cancer cells [ 28 ], migration of leukemia cells [ 29 , 30 ], as well as help characterize cancer stem cells of hepatocellular carcinoma [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Antrodia cinnamomeaalleviates cisplatin-induced hepatotoxicity and enhances chemo-sensitivity of line-1 lung carcinoma xenografted in BALB/cByJ mice

et al. 2015

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Whereas cisplatin (cis-diamminedichloroplatinum II) is a first-line medicine to treat solid cancerous tumors, it often causes serious side effects. New medicines that have an equivalent or even better therapeutic effect but with free or less side effects than cisplatin are highly anticipated in cancer therapy. Recent reports revealed that Antrodia cinnamomea (AC) possesses hepatoprotective activity in addition to anticancer. In this study, we wanted to know whether AC enhances chemo-sensitivity of cisplatin and/or alleviates cisplatin-induced hepatotoxicity, as well as the underlying mechanisms thereof. Our results indicated that AC inhibited proliferation of line-1 lung carcinoma cells and rescued hepatic HepG2 cells from cisplatin-induced cell death in vitro. The fact is that AC and cisplatin synergized to constrain growth of line-1 lung carcinoma cells in BALB/cByJ mice. Quantitative real-time PCR further revealed that AC promoted expression of apoptosis-related genes, while it decreased expression of NF-κB and VEGF in tumor tissues. In liver, AC reduced cisplatin-induced liver dysfunctions, liver inflammation and hepatic apoptosis in addition to body weight restoration. In summary, AC is able to increase cisplatin efficacy by triggering expression of apoptosis-related genes in line-1 lung cancer cells as well as to protect liver from tissue damage by avoiding cisplatin-induced hepatic inflammation and cell death.

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“…Growing evidences show that extracts, fermented products, or compounds isolated from A. cinnamomea possess growth inhibitory activity against various types of cancers. 8 , 9 Other than its infected fungus, A. cinnamomea , little is known about the bioactivity of this plant per se.…”

Section: Introductionmentioning

confidence: 99%

Ethanol extracts of Cinnamomum kanehirai Hayata leaves induce apoptosis in human hepatoma cell through caspase-3 cascade

Liu

Chen

Leu

et al. 2014

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Inducing apoptosis to susceptible cells is the major mechanism of most cytotoxic anticancer drugs in current use. Cinnamomum kanehirai Hayata (Lauraceae), a unique and native tree of Taiwan, is the major host for the medicinal fungus Antrodia cinnamomea which exhibits anti-cancer activity. Because of the scarcity of A. cinnamomea, C. kanehirai Hayata instead, is used as fork medicine in liver cancer. Here we observed the C. kanehirai Hayata ethanol extract could inhibit the cellular viability of both HepG2 and HA22T/VGH human hepatoma cell lines in a dose- and time-dependent manner. We found the mode of cell death was apoptosis according to cell morphological changes by Liu’s stain, oligonucleosomal DNA fragmentation by gel electrophoresis, externalization of phosphotidyl serine by detecting Annexin V and hypoploid population by cell cycle analysis. Our results showed that the extracts caused cleavage of caspase-3 and increased enzyme activity of caspase-8 and caspase-9. Caspase 3 inhibitor partially reversed the viability inhibition by the extract. Furthermore, the up-regulation of Bax and down-regulation of Bcl-2 were also noted by the extract treatment. In conclusion, C. kanehirai Hayata ethanol extract induced intrinsic pathway of apoptosis through caspase-3 cascade in human hepatoma HA22T/VGH and HepG2 cells, which might shed new light on hepatoma therapy.

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Medicinal FungusAntrodia cinnamomeaInhibits Growth and Cancer Stem Cell Characteristics of Hepatocellular Carcinoma

Cited by 13 publications

References 25 publications

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

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 cinnamomeaalleviates cisplatin-induced hepatotoxicity and enhances chemo-sensitivity of line-1 lung carcinoma xenografted in BALB/cByJ mice

Ethanol extracts of Cinnamomum kanehirai Hayata leaves induce apoptosis in human hepatoma cell through caspase-3 cascade

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