Ganoderma tsugaeExtract Inhibits Growth of HER2-Overexpressing Cancer Cells via Modulation of HER2/PI3K/Akt Signaling Pathway

Abstract

Ganoderma, also known as Lingzhi or Reishi, has been used for medicinal purposes in Asian countries for centuries. It is a medicinal fungus with a variety of biological properties including immunomodulatory and antitumor activities. In this study, we investigated the molecular mechanisms by which Ganoderma tsugae (GT), one of the most common species of Ganoderma, inhibits the proliferation of HER2-overexpressing cancer cells. Here, we show that a quality assured extract of GT (GTE) inhibited the growth of HER2-overexpressing cancer cells in vitro and in vivo and enhanced the growth-inhibitory effect of antitumor drugs (e.g., taxol and cisplatin) in these cells. We also demonstrate that GTE induced cell cycle arrest by interfering with the HER2/PI3K/Akt signaling pathway. Furthermore, GTE curtailed the expression of the HER2 protein by modulating the transcriptional activity of the HER2 gene and the stability/degradation of the HER2 protein. In conclusion, this study suggests that GTE may be a useful adjuvant therapeutic agent in the treatment of cancer cells that highly express HER2.

Mycosphere Essays 20: Therapeutic potential of Ganoderma species: Insights into its use as traditional medicine

“…Furthermore, GT induces cellular apoptosis via induction of a mitochondria/caspase pathway and suppression of cell proliferation by through down-regulation of the PI3K/Akt signaling pathway ). Kuo et al (2013) revealed G. tsugae extract inhibits cancer cell growth and induces cell cycle arrest via modulation of the HER2/PI3K/Akt signaling pathway. Furthermore, combining G. tsugae extract with taxol or cisplatin significantly slows the growth of HER2-overexpressing cancer cells.…”

“…In vitro studies of G. tsugae indicated that administration of G. tsugae extract (GTE) induced G1 phase arrest via modulating cyclins D1, E, p21, and p27 in the cell cycle in ovarian cancer and breast cancer cells. Furthermore, G. tsugae arrests cyclin and cdks in HER2/ PI3K/Akt signaling which inhibit the growth of HER2 overexpressing cancer cells (Kuo et al 2013). Chiang et al (2014) prepared nano/submicrometer particles from G. tsugae and both nano/submicrometer and hot-water extract G. tsugae exhibited no mutagenic potential to Salmonella typhimurium tester strains.…”

Triterpenes in cancer: significance and their influence

“…Cucurbitacin STAT3, STAT5, JAK2, JAK-STAT, c-myc, cyclins, survivin, p53, Bcl-xL, Bcl-2, AMPK, mTORC1/p70S6K [85,86] Withanolide TNF, TNFR 1, mTOR, Akt, 4EBP1, p70-S6K, SK3b, b-catenin, Notch1 cleavage, and cyclin D1, NF-jB [87,88] Lupeol NF-jB, PI3K, Akt, Ras protein, MAPK [89,90] Pristimerin NF-jB, Bax, Bcl-2, Bcl-xL, VEGFR2, ERK1/2, mTOR, ribosomal protein S6 kinase [91,92] Platycodon D MAPK, ERK, p38, JNK, NF-jB, PI3K, mTOR [93] Ursolic acid STAT3, NF-jB, p53, mTORC1, PI3K, Bcl-2, Bax, PKC, [94] Alisol B Bax, Bcl-2, cell cycle arrest, caspase-3, caspase-9, PI3K, CaMKK, AMPK, mTOR [95,96] Nimbolide IGF-IRb, IGFBP-3, MEK, pERK1/2, p38, PTEN, Raf-1, PI3K, cell cycle [97] Glycyrrhizin NF-jB, STAT3, TNF-a, interleukin-1b (IL-1b), ERK, JNK, and PI3K/AKT and Akt/ mTOR/STAT3 [98,99] Ganoderma tsugae PI3K, Akt, MAPK, cyclins D1, p21, p27 [100,101] caspase-9 activation. Asiatic acid induces ERK1/2, p38, MAPKs, but not JNK [77].…”

“…In vitro studies of G. tsugae indicated that administration of G. tsugae extract (GTE) induced G1 phase arrest via modulating cyclins D1, E, p21, and p27 in the cell cycle in ovarian cancer and breast cancer cells. G. tsugae arrests cyclin and cdks in HER2/ PI3K/Akt signaling which inhibit the growth of HER2 overexpressing cancer cells [100].…”

Growth-suppressive effect of berberine on endometrial carcinoma cells: Role of mitochondrial and PI3K/Akt pathway

“…Cell proliferation was measured using an MTT assay as previously described (Kuo et al, 2013). Briefly, cells were seeded at a density of 9000 cells/well onto 96-well plates and incubated overnight in a medium containing 10% FBS.…”