Engeletin suppresses lung cancer progression by inducing apoptotic cell death through modulating the XIAP signaling pathway: A molecular mechanism involving ER stress

Breast cancer is the most common cancer in women worldwide and the second most common cancer overall. Autocrine growth hormone (GH) expression induced cell proliferation, growth, invasion-metastasis in vitro and in vivo breast cancer models. Moreover, forced GH signaling acts as a drug resistance profile in breast cancer cell lines against chemotherapeutic drugs such as tamoxifen, mitomycin C, doxorubicin and curcumin. Triptolide, an active plant extract from Tripterygium wilfordii, has been shown to induce apoptotic cell death in various cancer cells such a prostate, colon, breast cancer. Metformin, a common therapeutic agent for type II Diabetes mellitus, has been shown to induce autophagy, endoplasmic reticulum (ER) stress and apoptotic cell death in cancer cells. Our aim is to demonstrate the potential effect of metformin on triptolide-mediated drug resistance in autocrine GH expressing MDA-MB-231 breast cancer cells through Endoplasmic reticulum (ER) stress. Autocrine GH-mediated triptolide (20 nM) resistance overcame by metformin (2 mM) co-teatment in MDA-MB231 breast cancer cells through accelerating cell viability loss, growth inhibition compared to alone triptolide treatment. Combined treatment increased apoptotic cell death via CHOP activation, IRE1α upregulation. Consequently, we suggest that triptolide can be more effective with metformin combination in MDA-MB-231 GH+ drug resistant breast cancer cells.

Download Full-text

AMPK and Akt Determine Apoptotic Cell Death following Perturbations of One-Carbon Metabolism by Regulating ER Stress in Acute Lymphoblastic Leukemia

Molecular Cancer Therapeutics ◽

10.1158/1535-7163.mct-10-0777 ◽

2011 ◽

Vol 10 (3) ◽

pp. 437-447 ◽

Cited By ~ 59

Author(s):

Jeffim N. Kuznetsov ◽

Guy J. Leclerc ◽

Gilles M. Leclerc ◽

Julio C. Barredo

Keyword(s):

Cell Death ◽

Acute Lymphoblastic Leukemia ◽

Er Stress ◽

Carbon Metabolism ◽

Apoptotic Cell ◽

Lymphoblastic Leukemia ◽

Apoptotic Cell Death ◽

One Carbon Metabolism

Download Full-text

Bufalin Induces Apoptotic Cell Death in Human Nasopharyngeal Carcinoma Cells through Mitochondrial ROS and TRAIL Pathways

The American Journal of Chinese Medicine ◽

10.1142/s0192415x19500125 ◽

2019 ◽

Vol 47 (01) ◽

pp. 237-257 ◽

Cited By ~ 10

Author(s):

En-Yun Su ◽

Yung-Lin Chu ◽

Fu-Shin Chueh ◽

Yi-Shih Ma ◽

Shu-Fen Peng ◽

...

Keyword(s):

Cell Death ◽

Nasopharyngeal Carcinoma ◽

Er Stress ◽

Apoptotic Cell ◽

Morphological Changes ◽

Chromatin Condensation ◽

Apoptotic Cell Death ◽

Dapi Staining ◽

Human Nasopharyngeal Carcinoma ◽

Associated Proteins

The aim of this study was to investigate the effects of bufalin on human nasopharyngeal carcinoma NPC-TW 076 cells in vitro. Bufalin is a cardiotonic steroid and a key active ingredient of the Chinese medicine ChanSu. The extracts of Chansu are used for various cancer treatments in China. In the present study, bufalin induced cell morphological changes, decreased total cell viability and induced G2/M phase arrest of cell cycle in NPC-TW 076 cells. Results also indicated that bufalin induced chromatin condensation (cell apoptosis) and DNA damage by DAPI staining and comet assay, respectively. The induced apoptotic cell death was further confirmed by annexin-V/PI staining assay. In addition, bufalin also increased ROS and Ca[Formula: see text] production and decreased the levels of [Formula: see text]. Furthermore, the alterations of ROS, ER stress and apoptosis associated protein expressions were investigated by Western blotting. Results demonstrated that bufalin increased the expressions of ROS associated proteins, including SOD (Cu/Zn), SOD2 (Mn) and GST but decreased that of catalase. Bufalin increased ER stress associated proteins (GRP78, IRE-1[Formula: see text], IRE-1[Formula: see text], caspase-4, ATF-6[Formula: see text], Calpain 1, and GADD153). Bufalin increased the pro-apoptotic proteins Bax, and apoptotic associated proteins (cytochrome c, caspase-3, -8 and -9, AIF and Endo G) but reduced anti-apoptotic protein Bcl-2 in NPC-TW 076 cells. Furthermore, bufalin elevated the expressions of TRAIL-pathway associated proteins (TRAIL, DR4, DR5, and FADD). Based on these findings, we suggest bufalin induced apoptotic cell death via caspase-dependent, mitochondria-dependent and TRAIL pathways in human nasopharyngeal carcinoma NPC-TW 076 cells.

Download Full-text