Ganoderma tsugaeInduces S Phase Arrest and Apoptosis in Doxorubicin-Resistant Lung Adenocarcinoma H23/0.3 Cells via Modulation of the PI3K/Akt Signaling Pathway

Abstract

Ganoderma tsugae (GT) is a traditional Chinese medicine that exhibits significant antitumor activities against many types of cancer. This study investigated the molecular mechanism by which GT suppresses the growth of doxorubicin-resistant lung adenocarcinoma H23/0.3 cells. Our results reveal that GT inhibits the viability of H23/0.3 cells in vitro and in vivo and sensitizes the growth suppression effect of doxorubicin on H23/0.3 cells. The data also show that GT induces S phase arrest by interfering with the protein expression of cyclin A, cyclin E, CDK2, and CDC25A. Furthermore, GT induces cellular apoptosis via induction of a mitochondria/caspase pathway. In addition, we also demonstrate that the suppression of cell proliferation by GT is through down-regulation of the PI3K/Akt signaling pathway. In conclusion, this study suggests that GT may be a useful adjuvant therapeutic agent in the treatment of lung cancer.

The novel miR-9500 regulates the proliferation and migration of human lung cancer cells by targeting Akt1

“…The protein levels of cyclin E and CDK2 were modulated by the downregulation of AKT1, whereas the protein levels of Rb were slightly decreased (Figure 4c). Some studies have shown that the inhibition of p-AKT and AKT promotes the downregulation of cyclin E. 41 The downregulation of cell cycle regulatory proteins, such as Rb, cyclin E, and CDK2, induces an S-phase cell cycle arrest. 42 Actually, the miR-9500-transfected A549 cells had an increased number of cells in the G1 phase, as well as a reduced number of S and G2/M phase cells, according to flow cytometry analysis.…”

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

“…In addition to the anticancer agents, a number of TCMs and botanical products have been shown to be effective and useful adjuvant agents for the treatment of HER2-overexpressing cancer [5, 6, 26]. Ganoderma tsugae (GT), one of the most common species of Ganoderma cultivated in Taiwan, has been shown to have antiproliferative effects on human cancer cells [15, 16, 18]. In this study, we report for the first time that the extract of GT (GTE) has a distinct growth-inhibitory effect on HER2-overexpressing cancer cells in vitro (Figures 1(a)–1(c)) and in vivo (Figure 5(a)).…”

“…A number of TCMs (e.g., GT) exhibit marked growth-inhibitory effects on cancer cells via disruption of cell cycle progression. Previous reports show that GT inhibits cell proliferation by inducing cell cycle arrest in the G2/M phase in Hep3B hepatoma and COLO205 colorectal cancer cells [15, 17] and in the S phase in H23/0.3 lung adenocarcinoma cells [18]. In this study, our in vitro results indicate that GTE treatment induces G1 phase arrest via modulation of cell cycle regulators (e.g., cyclins D1 and E, p21, and p27) in HER2-overexpressing SKOV-3 ovarian cancer and BT-474 breast cancer cells (Figure 2 and Supplementary Figure S4).…”

“…The quality of the GTEs was assessed as described previously [18, 19]. Briefly, the genomic bioresponse to the GTEs was determined in SKOV-3 cells treated with 0.5 mg/mL of GTE.…”

“…In addition, Ganoderma tsugae (GT), another well-cultivated species of Ganoderma , has been shown to have many biological and pharmacological properties, such as antiautoantibody formation [10], antifibrosis [11], antiinflammation [12], and antioxidation characteristics [13]. A number of reports show that GT has growth-inhibitory effects in a variety of human cancer cells, such as MDA-MB-231 and MCF-7 breast cancer cells [14], COLO 205 colorectal cancer cells [15], A431 epidermoid carcinoma cells [16], Hep3B hepatoma cells [17], and H23 and H23/0.3 lung adenocarcinoma cells [18]. Although GT has antitumor activity in many human cancer cells, the mechanisms that underlie its growth-inhibitory effect on HER2-overexpressing cancer cells remain unclear.…”