Z-360 Suppresses Tumor Growth in MIA PaCa-2-bearing Mice via Inhibition of Gastrin-induced Anti-Apoptotic Effects

Shiomi, Yoshihiro; Yoshimura, Masashi; Kuki, Kazumasa; Hori, Yûko; Tanaka, Takao

doi:10.21873/anticanres.11800

Cited by 3 publications

(2 citation statements)

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“…These data suggest that caspase 8 is involved in the apoptosis of MIA PaCa-2. Although, canonically, the activation of the extrinsic pathway (via caspase 8) triggers the induction of the intrinsic pathway, therefore caspase 9 activation, in pancreatic cancer cells [ 28 , 29 ], the activation of caspase 9 by HCA seems to be unrelated to the cell death induction. Hence, HCA would appear to induce apoptosis mainly through the extrinsic or death receptor-dependent pathway.…”

Section: Resultsmentioning

confidence: 99%

HCA (2-Hydroxy-Docosahexaenoic Acid) Induces Apoptosis and Endoplasmic Reticulum Stress in Pancreatic Cancer Cells

Beteta-Göbel

Miralles

Fernández-Díaz

et al. 2022

IJMS

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Pancreatic cancer has a high mortality rate due to its aggressive nature and high metastatic rate. When coupled to the difficulties in detecting this type of tumor early and the lack of effective treatments, this cancer is currently one of the most important clinical challenges in the field of oncology. Melitherapy is an innovative therapeutic approach that is based on modifying the composition and structure of cell membranes to treat different diseases, including cancers. In this context, 2-hydroxycervonic acid (HCA) is a melitherapeutic agent developed to combat pancreatic cancer cells, provoking the programmed cell death by apoptosis of these cells by inducing ER stress and triggering the production of ROS species. The efficacy of HCA was demonstrated in vivo, alone and in combination with gemcitabine, using a MIA PaCa-2 cell xenograft model of pancreatic cancer in which no apparent toxicity was evident. HCA is metabolized by α-oxidation to C21:5n-3 (heneicosapentaenoic acid), which in turn also showed anti-proliferative effect in these cells. Given the unmet clinical needs associated with pancreatic cancer, the data presented here suggest that the use of HCA merits further study as a potential therapy for this condition.

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Section: Resultsmentioning

confidence: 99%

HCA (2-Hydroxy-Docosahexaenoic Acid) Induces Apoptosis and Endoplasmic Reticulum Stress in Pancreatic Cancer Cells

Beteta-Göbel

Miralles

Fernández-Díaz

et al. 2022

IJMS

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“…In the world, pancreatic cancer (PC) is ranked the fourth highest cause of cancer-related deaths and the fourteenth most common cancer [1]. By the year 2030, it is predicted that it would become the second-most common cause of cancer-related deaths [2]. Pancreatic cancer is mainly divided into two types: (i) pancreatic adenocarcinoma (PA), the most common (85% of cases), arises in exocrine glands of the pancreas, and (ii) pancreatic neuroendocrine tumor (Pan-NET) which occurs in the endocrine tissue of the pancreas and less common [3].…”

Section: Introductionmentioning

confidence: 99%

Predicting the bioactivity of 2-alkoxycarbonylallyl esters as potential antiproliferative agents against pancreatic cancer (MiaPaCa-2) cell lines: GFA-based QSAR and ELM-based models with molecular docking

Oyeneyin

Obadawo

Olanrewaju

et al. 2021

Journal of Genetic Engineering and Biotechnology

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Background The number of cancer-related deaths is on the increase, combating this deadly disease has proved difficult owing to resistance and some serious side effects associated with drugs used to combat it. Therefore, scientists continue to probe into the mechanism of action of cancer cells and designing novel drugs that could combat this disease more safely and effectively. Here, we developed a genetic function approximation model to predict the bioactivity of some 2-alkoxyecarbonyl esters and probed into the mode of interaction of these molecules with an epidermal growth factor receptor (3POZ) using the three-dimensional quantitative structure activity relationship (QSAR), extreme learning machine (ELM), and molecular docking techniques. Results The developed QSAR model with predicted (R2pred) of 0.756 showed that the model was fit to be validated parameter for a built model and also proved that the developed model could be used in practical situation, R2 for training set (0.9929) and test set (0.8397) confirmed that the model could successfully predict the activity of new compounds due to its correlation with the experimental activity, the models generated with ELM models showed improved prediction of the activity of the molecules. The lead compounds (22 and 23) had binding energies of −6.327 and −7.232 kcalmol−1 for 22 and 23 respectively and displayed better inhibition at the binding sites of 3POZ when compared with that of the standard drug, chlorambucil (−6.0 kcalmol−1). This could be attributed to the presence of double bonds and the α-ester groups. Conclusion The QSAR and ELM models had good prognostic ability and could be used to predict the bioactivity of novel anti-proliferative drugs.

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Knockdown of Gastrin Promotes Apoptosis of Gastric Cancer Cells by Decreasing ROS Generation

Liu

Zhu

Liu

et al. 2021

BioMed Research International

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Overexpressed gastrin is reported to promote oncogenesis and development of gastric cancer by inhibiting apoptosis of cancer cells; however, the underlying mechanism remains unclear. Our study is aimed at revealing the mechanism underlying the effect of gastrin on apoptosis of gastric cancer cells. Gastrin-interfering cell line was constructed by stably transfecting gastrin-specific pshRNA plasmid to gastric cancer cell line BGC-823. Then, differentially expressed proteins between untreated BGC-823 and gastrin-interfering BGC-823 cell lines were detected by the iTRAQ technique. GO and KEGG analysis was used to analyze the differentially expressed genes that code these differentially expressed proteins. The Annexin V-FITC staining assay was used to detect gastric cancer cell apoptosis. The DCFH-DA fluorescent probe staining assay was used to measure intracellular ROS. Mitochondrial membrane potential was detected by flow cytometry. Western blot was used to analyze the mitochondria respiratory chain proteins and apoptosis-related proteins. A total of 107 differentially expressed proteins were identified by iTRAQ. GO and KEGG analysis showed that proteins coded by the corresponding differentially expressed genes were mainly enriched in the mitochondrial oxidative respiratory chain, and the expression of three proteins (COX17, COX5B, ATP5J) was upregulated. The three proteins with higher scores were verified by Western blot. The apoptosis rate of the gastrin knockdown cancer cell was significantly increased; meanwhile, gastrin knockdown leads to increase of membrane potential and decrease of intracellular ROS production. Additionally, Bax was significantly increased, whereas NF-κB-p65 and Bcl-2 were downregulated after knockdown of gastrin. Concomitantly, pretreatment with NAC reversed the effect of gastrin on the Bax and Bcl-2 expression. Gastrin promotes the production of ROS from mitochondria, activates NF-κB, and inhibits apoptosis via modulating the expression level of Bcl-2 and Bax.

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Z-360 Suppresses Tumor Growth in MIA PaCa-2-bearing Mice via Inhibition of Gastrin-induced Anti-Apoptotic Effects

Abstract: These results suggest that Z-360 exerts an anti-tumor effect through a reduction in anti-apoptosis factors by blocking CCK2R.

Cited by 3 publications

References 30 publications

HCA (2-Hydroxy-Docosahexaenoic Acid) Induces Apoptosis and Endoplasmic Reticulum Stress in Pancreatic Cancer Cells

HCA (2-Hydroxy-Docosahexaenoic Acid) Induces Apoptosis and Endoplasmic Reticulum Stress in Pancreatic Cancer Cells

Predicting the bioactivity of 2-alkoxycarbonylallyl esters as potential antiproliferative agents against pancreatic cancer (MiaPaCa-2) cell lines: GFA-based QSAR and ELM-based models with molecular docking

Knockdown of Gastrin Promotes Apoptosis of Gastric Cancer Cells by Decreasing ROS Generation

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