Direct Evidence of the Link Between Energetic Metabolism and Proliferation Capacity of Cancer Cells In Vitro

Author(s):  
Géraldine De Preter ◽  
Pierre Danhier ◽  
Paolo E. Porporato ◽  
Valéry L. Payen ◽  
Bénédicte F. Jordan ◽  
...  
2020 ◽  
Author(s):  
Xiaofei Jiang ◽  
Mingqing Shi ◽  
Miao Sui ◽  
Yizhen Yuan ◽  
Shuang Zhang ◽  
...  

Abstract Background: Cervical cancer continues to be the leading cause of cancer deaths among women worldwide. Oleanolic acid (OA) is a naturally occurring substance found in the leaves, fruits, and rhizomes of plants that has anti-cancer activity. Methods: We used tumor-bearing mice as the animal model and Hela cell as cell models. Western blot was used for detecting the expression of proteins in ferroptosis related proteins acyl-CoA synthase long-chain family member 4 (ACSL4), ferritin heavy chain (FTH1), transferrin receptor (TfR1) and glutathione peroxidase 4 (GPX4) in vivo and in vitro. MTT and EdU was for the detection of the viability of Hela cells. Results: In vivo experiments showed that OA significantly reduced the size and mass of cervical cancer tumors. In vitro experiments showed that OA significantly reduced the viability and proliferation capacity of Hela cells. In both in vivo and in vitro assays, OA increased the level of oxidative stress and Fe2+ content, and increased the expression of ferroptosis related proteins. We found high expression of ACSL4 in both xenograft models and cervical carcinoma cells. Meanwhile, knockdown of ACSL4 expression using shRNA in cervical cancer cells significantly increased cell viability and proliferation. In addition, decreased ROS levels and GPX4 were detected in ACSL4 knockdown cervical cancer cells, suggesting that ACSL4 inhibition may contribute to the reduction of ferroptosis within Hela cells and thus improve Hela cell survival. Conclusion: Promotion of ACSL4 dependent ferroptosis through OA may be an effective approach to treat cervical cancer.


2022 ◽  
Vol 67 (4) ◽  
pp. 83-90
Author(s):  
Yuqiang Shan ◽  
Wencheng Kong ◽  
Akao Zhu ◽  
Jiangtao Li ◽  
Huicheng Jin ◽  
...  

Nowadays, pancreatic cancer has been recognized as one of the most fatal malignancies worldwide, the molecular mechanism of which is still not fully understood. In this study, we aimed to uncover the fundamental functions of the eukaryotic translation initiation factor 3H subunit (EIF3H) in the development and progression of pancreatic cancer. Firstly, the results of immunohistochemical (IHC) staining revealed that EIF3H was highly expressed in pancreatic cancer. Moreover, lentiviruses were used to deliver shRNAs into pancreatic cancer cells for silencing EIF3H. Furthermore, the loss-of-function assays demonstrated that knockdown of EIF3H could inhibit the progression of pancreatic cancer cells by reducing proliferation capacity, promoting apoptosis, arresting cell cycle in G2 and suppressing cell migration. In summary, EIF3H may play a critical role in the development and progression of pancreatic cancer, which possesses the potential to act as a therapeutic target for pancreatic cancer treatment.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuan Chen ◽  
Yiting Geng ◽  
Junchao Huang ◽  
Dan Xi ◽  
Guoping Xu ◽  
...  

Abstract Background CircRNAs play crucial roles in multiple tumours. However, the functions of most circRNAs in cervical cancer remain unclear. Methods This study collected GSE113696 data from the GEO database to search for differentially expressed circRNAs in cervical cancer. Quantitative reverse transcription PCR was used to detect the expression level of circNEIL3 in cervical cancer cells and tissues. Then, functional experiments in vitro and in vivo were performed to evaluate the effects of circNEIL3 in cervical cancer. Results CircNEIL3 was highly expressed in cervical cancer. In vivo and in vitro experiments verified that circNEIL3 enhanced the proliferation capacity of cervical cancer cells. RNA immunoprecipitation, luciferase reporter assay, pull-down assay, and fluorescent in situ hybridization confirmed the interaction between circNEIL3 and miR-137 in cervical cancer. A luciferase reporter assay showed that circNEIL3 adsorbed miR-137 and upregulated KLF12 to regulate the proliferation of cervical cancer cells. Conclusions CircNEIL3 is an oncogene in cervical cancer and might serve as a ceRNA that competitively binds to miR-137, thereby indirectly upregulating the expression of KLF12 and promoting the proliferation of cervical cancer cells.


2018 ◽  
Author(s):  
F Guo ◽  
Z Yang ◽  
J Xu ◽  
J Sehouli ◽  
AE Albers ◽  
...  

Author(s):  
Mayson H. Alkhatib ◽  
Dalal Al-Saedi ◽  
Wadiah S. Backer

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.


2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Lisni Noraida Waruwu ◽  
Maria Bintang ◽  
Bambang Pontjo Priosoeryanto

Green tea (Camellia sinensis) is one of traditional plants that have the potential as an anticancer. The sample used in this research commercial green tea extract. The purpose of this study was to test the antiproliferation activity of green tea extract on breast cancer cell MCM-B2 in vitro. Green tea extract fractionated using three solvents, ie water, ethanol 70%, and n-hexane. Extract and fraction of green tea water have value Lethality Concentration 50 (LC50) more than 1000 ppm. The fraction of ethanol 70% and n-hexane had an LC50 value of 883.48 ppm and 600.56 ppm, respectively. The results of the phytochemical screening of green tea extract are flavonoids, tannins, and saponins, while the phytochemical screening results of n-hexane fraction are flavonoids and tannins. Antiproliferation activity was tested on breast cancer cells MCM-B2 and normal cells Vero by trypan blue staining method. The highest MCM-B2 cell inhibitory activity was achieved at a concentration of 13000 ppm green tea extract and 1000 ppm of n-hexane fraction, 59% and 59%, respectively. The extract and n-hexane fraction of green tea are not toxic to normal Vero cells characterized by not inhibiting normal cell proliferation. Keywords: antiproliferative, cancer cell MCM-B2, commercial green tea, cytotoxicity


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