Curcumin inhibits autocrine growth hormone-mediated invasion and metastasis by targeting NF-κB signaling and polyamine metabolism in breast cancer cells

Amino Acids ◽  
2018 ◽  
Vol 50 (8) ◽  
pp. 1045-1069 ◽  
Author(s):  
Ajda Coker-Gurkan ◽  
Merve Celik ◽  
Merve Ugur ◽  
Elif-Damla Arisan ◽  
Pinar Obakan-Yerlikaya ◽  
...  
Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 9
Author(s):  
Amani Abdulmunem ◽  
Pınar Obakan-Yerlikaya ◽  
Elif-Damla Arisan ◽  
Ajda Coker-Gurkan

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.


Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1569
Author(s):  
Derya Bulut ◽  
Ajda Coker-Gurkan ◽  
Recep Genc ◽  
Elif Damla Arisan ◽  
Pınar Obakan-Yerlikaya ◽  
...  

Curcumin, a plant derived natural compound, has anti-oxidant, anti-proliferative and apoptotic effect on various cancer cells such as prostate, colon and breast cancer. Autocrine growth hormone (GH) expression induced breast cancer invasion-metastasis has been reported in vivo and in vitro cancer models. Autophagy is a vesicule-mediated clearance mechanism and one of the handicap against drug-induced apoptotic cell death. In this study, our aim was to investigate the molecular machinery of curcumin induced apoptotic cell death under autophagy inhibition conditions in autocrine GH expressing MDA-MB-231 and T47D breast cancer cells. Although autocrine GH induced curcumin resistance, this effect was slightly prevented by time-dependent curcumin treatment in MDA-MB-231 and T47D breast cancer cells. In addition, curcumin induced autophagy vacuole formation was determined by acridine orange staining in MDA-MB-231 and T47D wt/GH+ breast cancer cells. Moreover, curcumin triggered autophagy through upregulating Beclin-1, Atg3, Atg12 expressions and LC3 cleavage in each cell line. Concomitantly, BiP, IRE1α and Calreticulin expressions were upregulated following 3 h curcumin exposure in MDA-MB-231 wt and GH+ cells. According to MTT cell viability assay, autocrine GH-mediated curcumin resistance was overcome by bafilomycin and curcumin co-treatment in MDA-MB-231 and T47D GH+ cells. Moreover, curcumin and bafilomycin co-treatment induced cell cycle arrest at G1 phase in MDA-MB-231 GH+ cells, G2/M arrest in T47D GH+ breast cancer cells. In conclusion, autocrine GH-triggered curcumin resistance was overcome by autophagy inhibition condition by bafilomycin treatment in a dose-dependent manner in MDA-MB-231 and T47D GH+ breast cancer cells.


2007 ◽  
Vol 170 (6) ◽  
pp. 2112-2121 ◽  
Author(s):  
Khalid Sossey-Alaoui ◽  
Alfiya Safina ◽  
Xiurong Li ◽  
Mary M. Vaughan ◽  
David G. Hicks ◽  
...  

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