A Triterpene Lactone from Callistemon citrinus Inhibits the PANC‐1 Human Pancreatic Cancer Cells Viability through Suppression of Unfolded Protein Response

2020 ◽  
Vol 17 (10) ◽  
Author(s):  
Ahmed M. Tawila ◽  
Sijia Sun ◽  
Min Jo Kim ◽  
Ashraf M. Omar ◽  
Dya Fita Dibwe ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Unfolded Protein Response ◽  
Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Unfolded Protein ◽  
Pancreatic Cancer Cells ◽  
Protein Response

scholarly journals Selective inhibition of unfolded protein response induces apoptosis in pancreatic cancer cells

Oncotarget ◽  
2014 ◽  
Vol 5 (13) ◽  
pp. 4881-4894 ◽  
Author(s):  
Wenwen Chien ◽  
Ling-Wen Ding ◽  
Qiao-Yang Sun ◽  
Lucia A. Torres-Fernandez ◽  
Siew Zhuan Tan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Unfolded Protein Response ◽  
Cancer Cells ◽  
Selective Inhibition ◽  
Unfolded Protein ◽  
Pancreatic Cancer Cells ◽  
Protein Response

scholarly journals NUCB1 Suppresses Growth and Shows Additive Effects With Gemcitabine in Pancreatic Ductal Adenocarcinoma via the Unfolded Protein Response

2021 ◽  
Vol 9 ◽  
Author(s):  
Yong-Qiang Hua ◽  
Ke Zhang ◽  
Jie Sheng ◽  
Zhou-Yu Ning ◽  
Ye Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Unfolded Protein Response ◽  
Calcium Binding ◽  
Ductal Adenocarcinoma ◽  
Additive Effects ◽  
Unfolded Protein ◽  
Pancreatic Cancer Cells ◽  
The Unfolded Protein Response ◽  
Protein Response

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient prognosis. A cellular stress response mechanism called the unfolded protein response (UPR) has been implicated in PDAC progression. More recently, nucleobindin 1 (NUCB1), a calcium-binding protein, has been shown to control the UPR but its precise role in PDAC has not been explored. Here, we found that downregulation of NUCB1 was associated with poor prognosis in patients with PDAC. Functionally, NUCB1 overexpression suppressed pancreatic cancer cell proliferation and showed additive effects with gemcitabine (GEM) in vitro and in vivo. Moreover, by controlling ATF6 activity, NUCB1 overexpression suppressed GEM-induced UPR and autophagy. Last but not least, we uncovered METTL3-mediated m6A modification on NUCB1 5′UTR via the reader YTHDF2 as a mechanism for NUCB1 downregulation in PDAC. Taken together, our study revealed crucial functions of NUCB1 in suppressing proliferation and enhancing the effects of gemcitabine in pancreatic cancer cells and identified METTL3-mediated m6A modification as a mechanism for NUCB1 downregulation in PDAC.

scholarly journals An Emerging Role for the Unfolded Protein Response in Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 261
Author(s):  
Claire M. Robinson ◽  
Aaron Talty ◽  
Susan E. Logue ◽  
Katarzyna Mnich ◽  
Adrienne M. Gorman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Unfolded Protein Response ◽  
Cellular Response ◽  
Tumour Microenvironment ◽  
Pancreatic Stellate Cells ◽  
Paracrine Signalling ◽  
Unfolded Protein ◽  
Pancreatic Cancer Cells ◽  
The Unfolded Protein Response ◽  
Protein Response

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and one of the leading causes of cancer-associated deaths in the world. It is characterised by dismal response rates to conventional therapies. A major challenge in treatment strategies for PDAC is the presence of a dense stroma that surrounds the tumour cells, shielding them from treatment. This unique tumour microenvironment is fuelled by paracrine signalling between pancreatic cancer cells and supporting stromal cell types including the pancreatic stellate cells (PSC). While our molecular understanding of PDAC is improving, there remains a vital need to develop effective, targeted treatments. The unfolded protein response (UPR) is an elaborate signalling network that governs the cellular response to perturbed protein homeostasis in the endoplasmic reticulum (ER) lumen. There is growing evidence that the UPR is constitutively active in PDAC and may contribute to the disease progression and the acquisition of resistance to therapy. Given the importance of the tumour microenvironment and cytokine signalling in PDAC, and an emerging role for the UPR in shaping the tumour microenvironment and in the regulation of cytokines in other cancer types, this review explores the importance of the UPR in PDAC biology and its potential as a therapeutic target in this disease.

scholarly journals Triptolide activates unfolded protein response leading to chronic ER stress in pancreatic cancer cells

2014 ◽  
Vol 306 (11) ◽  
pp. G1011-G1020 ◽  
Author(s):  
Nameeta Mujumdar ◽  
Sulagna Banerjee ◽  
Zhiyu Chen ◽  
Veena Sangwan ◽  
Rohit Chugh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Death ◽  
Stress Response ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Initiation Factor ◽  
Unfolded Protein ◽  
Pancreatic Cancer Cells ◽  
Cancer Aggressiveness ◽  
Protein Response

Pancreatic cancer is a devastating disease with a survival rate of <5%. Moreover, pancreatic cancer aggressiveness is closely related to high levels of prosurvival mediators, which can ultimately lead to rapid disease progression. One of the mechanisms that enables tumor cells to evade cellular stress and promote unhindered proliferation is the endoplasmic reticulum (ER) stress response. Disturbances in the normal functions of the ER lead to an evolutionarily conserved cell stress response, the unfolded protein response (UPR). The UPR initially compensates for damage, but it eventually triggers cell death if ER dysfunction is severe or prolonged. Triptolide, a diterpene triepoxide, has been shown to be an effective compound against pancreatic cancer. Our results show that triptolide induces the UPR by activating the PKR-like ER kinase-eukaryotic initiation factor 2α axis and the inositol-requiring enzyme 1α-X-box-binding protein 1 axis of the UPR and leads to chronic ER stress in pancreatic cancer. Our results further show that glucose-regulated protein 78 (GRP78), one of the major regulators of ER stress, is downregulated by triptolide, leading to cell death by apoptosis in MIA PaCa-2 cells and autophagy in S2-VP10 cells.

In Vitro and In Vivo Antitumor Efficacy of Docetaxel and Sorafenib Combination in Human Pancreatic Cancer Cells

2010 ◽  
Vol 999 (999) ◽  
pp. 1-11
Author(s):  
P. Ulivi ◽  
C. Arienti ◽  
W. Zoli ◽  
M. Scarsella ◽  
S. Carloni ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Antitumor Efficacy ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells

scholarly journals Cyathus striatus Extract Induces Apoptosis in Human Pancreatic Cancer Cells and Inhibits Xenograft Tumor Growth In Vivo

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2017
Author(s):  
Lital Sharvit ◽  
Rinat Bar-Shalom ◽  
Naiel Azzam ◽  
Yaniv Yechiel ◽  
Solomon Wasser ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Culture Liquid ◽  
Human Pancreatic Cancer ◽  
P53 Signaling ◽  
Pancreatic Cancer Cells

Pancreatic cancer is a highly lethal disease with limited options for effective therapy and the lowest survival rate of all cancer forms. Therefore, a new, effective strategy for cancer treatment is in need. Previously, we found that a culture liquid extract of Cyathus striatus (CS) has a potent antitumor activity. In the present study, we aimed to investigate the effects of Cyathus striatus extract (CSE) on the growth of pancreatic cancer cells, both in vitro and in vivo. The proliferation assay (XTT), cell cycle analysis, Annexin/PI staining and TUNEL assay confirmed the inhibition of cell growth and induction of apoptosis by CSE. A Western blot analysis demonstrated the involvement of both the extrinsic and intrinsic apoptosis pathways. In addition, a RNAseq analysis revealed the involvement of the MAPK and P53 signaling pathways and pointed toward endoplasmic reticulum stress induced apoptosis. The anticancer activity of the CSE was also demonstrated in mice harboring pancreatic cancer cell line-derived tumor xenografts when CSE was given for 5 weeks by weekly IV injections. Our findings suggest that CSE could potentially be useful as a new strategy for treating pancreatic cancer.

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