scholarly journals Fungal Immunomodulatory Protein from Nectria haematococca Suppresses Growth of Human Lung Adenocarcinoma by Inhibiting the PI3K/Akt Pathway

2018 ◽  
Vol 19 (11) ◽  
pp. 3429 ◽  
Author(s):  
Yingying Xie ◽  
Shuying Li ◽  
Lei Sun ◽  
Shujun Liu ◽  
Fengzhong Wang ◽  
...  

Lung cancer is a common disease that is associated with poor prognosis. Fungal immunomodulatory protein from Nectria haematococca (FIP-nha) has potential as a lung cancer therapeutic; as such, illuminating its anti-tumor mechanism is expected to facilitate novel treatment options. Here, we showed that FIP-nha affects lung adenocarcinoma growth ex vivo and in vivo. Comparative quantitative proteomics showed that FIP-nha negatively regulates PI3K/Akt signaling and induces cell cycle arrest, autophagy, and apoptosis. We further demonstrated that FIP-nha suppresses Akt phosphorylation, leading to upregulation of p21 and p27 and downregulation of cyclin B1, cyclin D1, CDK2, and CDK4 expression, ultimately resulting in G1/S and G2/M cell cycle arrest. Meanwhile, FIP-nha-induced PI3K/Akt downregulation promotes A549 apoptosis by increasing the expression ratio of Bax/Bcl-2 and c-PARP and autophagy by decreasing the phosphorylation of mTOR. Thus, we comprehensively revealed the anti-tumor mechanism of FIP-nha, which inhibits tumor growth by modulating PI3K/Akt-regulated cell cycle arrest, autophagy, and apoptosis, and provided the basis for further application of fungal immunomodulatory proteins, especially FIP-nha.

2020 ◽  
Vol 21 (24) ◽  
pp. 9502
Author(s):  
Thanh Nam Phan ◽  
Okwha Kim ◽  
Manh Tuan Ha ◽  
Cheol Hwangbo ◽  
Byung-Sun Min ◽  
...  

Albanol B (ABN-B), an arylbenzofuran derivative isolated from mulberries, has been shown to have anti-Alzheimer’s disease, anti-bacterial and antioxidant activities. The aim of this study was to investigate the anti-cancer effect of this compound against lung cancer cells. The results show that ABN-B inhibited the proliferation of four human lung cancer cell lines (A549, BZR, H1975, and H226) and induced apoptosis, based on the cleavage of caspase-7 and PARP (poly (ADP-ribose) polymerase), as well as the downregulation of Bcl-2. ABN-B also induced cell cycle arrest at G2/M by down-regulating the expression of CKD1 (cyclin-dependent kinase 1) and cyclin B1, but up-regulating p21 (cyclin-dependent kinase inhibitor 1) expression. Notably, ABN-B increased the production of mitochondrial reactive oxygen species (ROS); however, treatment with mito-TEMPO (a specific mitochondrial antioxidant) blocked ABN-B-induced cell cycle arrest at G2/M and apoptosis, as well as the up-regulation of p21 and down-regulation of CDK1 and cyclin B1 induced by ABN-B. At the molecular level, ABN-B-induced mitochondrial ROS production increased the phosphorylation levels of AKT (protein kinase B) and ERK1/2 (extracellular signal-regulated kinase 1/2), while the inhibition of these kinases blocked the ABN-B-induced up-regulation of p21 and down-regulation of CDK1 and cyclin B1. Moreover, ABN-B significantly suppressed tumor growth in Ex-3LL (Lewis lung carcinoma) tumor-bearing mice. Taken together, these results suggest that ABN-B can exert an anti-cancer effect by inducing apoptosis and cell cycle arrest at G2/M through mitochondrial ROS production in lung cancer cells.


2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Tien-Chun Wang ◽  
Chih-Nan Fang ◽  
Chih-Chien Shen ◽  
Hui-Yu Wei ◽  
Yui-Ping Weng ◽  
...  

Lung cancer has long been one of the most deadly forms of cancer. The majority of lung cancers are of the non-small-cell lung cancer (NSCLC) type. Here we used the non-small-cell lung carcinoma cell line A549 to screen 15 different traditional Chinese herbal medicine (CHM) formulae to explore the possible mechanisms of alternative medicine in lung cancer therapy. We identified three formulae (Formulae 3, 5, and 14) that substantially decreased the survival of A549 cells but did not affect MRC5 normal lung tissue cells. Formula 14, Yang-Dan-Tang, a modified decoction of Ramulus Cinnamomi Cassiae, was chosen for further characterization. Flow cytometry analysis showed that treatment of Formula 14 induced cell cycle arrest in G1 and G2 phase without causing significant cell death. These results were also confirmed by Western blot analysis, with decreased expression of G1/S and G2/M promoting cell cycle machinery including cyclin D3, cyclin B1, CDK4, and CDK6. This study provides further insight into the possible working mechanism of Yang-Dan-Tang in patients.


2007 ◽  
Vol 120 (10) ◽  
pp. 905-909 ◽  
Author(s):  
Hong-li LI ◽  
Tong-shan WANG ◽  
Xiao-yu LI ◽  
Nan LI ◽  
Ding-zhi HUANG ◽  
...  

2021 ◽  
Vol 41 (3) ◽  
pp. 1357-1364
Author(s):  
WEI-TING CHEN ◽  
CHENG-HSIEN CHEN ◽  
HUNG-TAI SU ◽  
PO-FU YUEH ◽  
FEI-TING HSU ◽  
...  

Author(s):  
Kwangkho Kim ◽  
Ohman Kwon ◽  
Tae Ryu ◽  
Cho‑Rok Jung ◽  
Janghwan Kim ◽  
...  

2020 ◽  
Vol 11 (1) ◽  
pp. 456-471 ◽  
Author(s):  
Manling Hu ◽  
Jing Yang ◽  
Linlin Qu ◽  
Xuqian Deng ◽  
Zhiguang Duan ◽  
...  

Ginsenoside Rk1 can function as an antitumor modulator that induces apoptosis in lung adenocarcinoma cells by inhibiting NF-κB transcription and triggering cell cycle arrest.


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