Inhibition of aldehyde dehydrogenase by furazolidone nanoemulsion to decrease cisplatin resistance in lung cancer cells

2021 ◽  
Author(s):  
Mina Darooee ◽  
Vajihe Akbari ◽  
Azade Taheri
Keyword(s):  
Cancer Cells ◽  
Aldehyde Dehydrogenase ◽  
Cancer Survival ◽  
Cisplatin Resistance ◽  
A549 Cells ◽  
Therapeutic Resistance ◽  
Drug Resistant ◽  
Aldh Activity ◽  
Inhibitory Effects ◽  
Cytotoxic Potential

Aim: The overexpression of aldehyde dehydrogenase (ALDH) in cancer cells contributes to therapeutic resistance. Furazolidone (FUR) is a strong ALDH inhibitor. Methods: FUR nanoemulsion (NE) was formulated and tested for ALDH inhibitory activity in comparison with free FUR. The cytotoxic potential of cisplatin was evaluated in combination with free FUR and FUR NE. Results: The optimized FUR NE showed droplet size of 167.9 ± 3.1 nm and drug content of 84.2 ± 2.3%. FUR NE inhibited 99.75 ± 2.1% of ALDH activity while 25.0 ± 4.6% was inhibited by free FUR. FUR NE increased the sensitivity to cisplatin in A549 cells by more than tenfold by its ALDH inhibitory effects. Conclusion: This finding can be a promising approach to improve cancer survival in ALDH-positive drug-resistant cancers.

scholarly journals Research of the mechanism on miRNA193 in exosomes promotes cisplatin resistance in esophageal cancer cells

2019 ◽  
Author(s):  
Shifeng Shi ◽  
Xin Huang ◽  
Xiao Ma ◽  
Xiaoyan Zhu ◽  
Qinxian Zhang
Keyword(s):  
Cell Cycle ◽  
Drug Resistance ◽  
Esophageal Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cisplatin Resistance ◽  
High Expression ◽  
Drug Resistant ◽  
Cellular Resistance ◽  
Esophageal Cancer Cells

AbstractPurposeChemotherapy resistance of esophageal cancer is a key factor affecting the postoperative treatment of esophageal cancer. Among the media that transmit signals between cells, the exosomes secreted by tumor cells mediate information transmission between tumor cells, which can make sensitive cells obtain resistance. Although some cellular exosomes play an important role in tumor’s acquired drug resistance, the related action mechanism is still not explored specifically.MethodsTo elucidate this process, we constructed a cisplatin-resistant esophageal cancer cell line, and proved that exosomes conferring cellular resistance in esophageal cancer can promote cisplatin resistance in sensitive cells. Through high-throughput sequencing analysis of the exosome and of cells after stimulation by exosomes, we determined that the miRNA193 in exosomes conferring cellular resistance played a key role in sensitive cells acquiring resistance to cisplatin. In vitro experiments showed that miRNA193 can regulate the cell cycle of esophageal cancer cells and inhibit apoptosis, so that sensitive cells can acquire resistance to cisplatin. An in vivo experiment proved that miRNA193 can promote tumor proliferation through the exosomes, and provide sensitive cells with slight resistance to cisplatin.ResultsSmall RNA sequencing of exosomes showed that exosomes in drug-resistant cells have 189 up-regulated and 304 down-regulated miRNAs; transcriptome results showed that drug-resistant cells treated with drug-resistant cellular exosomes have 3446 high-expression and 1709 low-expression genes; correlation analysis showed that drug-resistant cellular exosomes mainly affect the drug resistance of sensitive cells through paths such as cytokine–cytokine receptor interaction, and the VEGF and Jak-STAT signaling pathways; miRNA193, one of the high-expression miRNAs in drug-resistant cellular exosomes, can promote drug resistance by removing cisplatin’s inhibition of the cell cycle of sensitive cells.ConclusionSensitive cells can become resistant to cisplatin through acquired drug-resistant cellular exosomes, and miRNA193 can make tumor cells acquire cisplatin resistance by regulating the cell cycle.

T4 Reduces Cisplatin Resistance by Inhibiting AEG-1 Gene Expression in Lung Cancer Cells

2020 ◽  
Author(s):  
Tianjiao Song ◽  
Xiaohong Lin ◽  
Pingting Huang ◽  
Yuqing Chen ◽  
Limin Chen
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
A549 Cells ◽  
Lethal Effect ◽  
Lung Cancer Cells ◽  
Chemotherapeutic Drugs ◽  
Lung Cancer Patients ◽  
Chemotherapy Drugs ◽  
Mdr 1

Abstract BackgroundLung cancer is one of the deadliest diseases in the world. Most lung cancer patients are resistant to chemotherapy drugs. In our study, we investigated whether T4 can reduce the resistance of lung cancer cells to chemotherapeutic drugs through the action of AEG-1.Materials and Methods1.A549 and A549/DDP cells were respectively transfected with overexpressing AEG-1 and knockdown AEG-1 plasmid. A549 and A549/DDP cells were added 0、25、50、100、200nM T4 respectively. 200nM T4 was selected for following experiments. A549/DDP cells were divided into A549/DDP empty group, T4 group, T4+AEG-1 overexpressing group. CCK8 assay was used to detect the proliferation of cells in each group. RT-qPCR and Western blotting were used to detect the expression of AEG-1 and MDR-1.ResultsAs expected, the expression of AEG-1 in A549 and A549/DDP cells is positively correlated with cisplatin resistance. When AEG-1 protein was overexpressed in A549 cells, the lethal effect of cisplatin on A549 cells was attenuated (all P<0.05). After AEG-1 protein was knocked down in A549/DDP cells, cisplatin was applied to the A549/DDP cells. The lethal effect was significantly increased compared to that in the control cells (all P<0.05). The expression of AEG-1 protein gradually decreased with increasing concentration of T4 in A549 and A549/DDP cells; The resistance to cisplatin was reduced after the addition of T4 to A549/DDP cells (P<0.05), and this effect was enhanced after transfection with the AEG-1 plasmid. ConclusionIn summary, T4 is important for increasing the sensitively of lung cancer cells to cisplatin. AEG-1 may be a key protein involved in this effect and may have an important impact on the survival rate of chemotherapy in patients with lung cancer in the future.

scholarly journals In Vivo Anti-Tumor Effects of Citral on 4T1 Breast Cancer Cells via Induction of Apoptosis and Downregulation of Aldehyde Dehydrogenase Activity

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3241 ◽  
Author(s):  
Nigjeh ◽  
Yeap ◽  
Nordin ◽  
Rahman ◽  
Rosli
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Aldehyde Dehydrogenase ◽  
Breast Cancer Cells ◽  
Oral Feeding ◽  
Aldh Activity ◽  
Secondary Tumors ◽  
4T1 Breast Cancer

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among females globally. The tumorigenic activities of cancer cells such as aldehyde dehydrogenase (ALDH) activity and differentiation have contributed to relapse and eventual mortality in breast cancer. Thus, current drug discovery research is focused on targeting breast cancer cells with ALDH activity and their capacity to form secondary tumors. Citral (3,7-dimethyl-2,6-octadienal), from lemon grass (Cymbopogon citrates), has been previously reported to have a cytotoxic effect on breast cancer cells. Hence, this study was conducted to evaluate the in vivo effect of citral in targeting ALDH activity of breast cancer cells. BALB/c mice were challenged with 4T1 breast cancer cells followed by daily oral feeding of 50 mg/kg citral or distilled water for two weeks. The population of ALDH+ tumor cells and their capacity to form secondary tumors in both untreated and citral treated 4T1 challenged mice were assessed by Aldefluor assay and tumor growth upon cell reimplantation in normal mice, respectively. Citral treatment reduced the size and number of cells with ALDH+ activity of the tumors in 4T1-challenged BALB/c mice. Moreover, citral-treated mice were also observed with smaller tumor size and delayed tumorigenicity after reimplantation of the primary tumor cells into normal mice. These findings support the antitumor effect of citral in targeting ALDH+ cells and tumor recurrence in breast cancer cells.

scholarly journals High aldehyde dehydrogenase activity does not protect colon cancer cells against TPCS2a-sensitized photokilling

2020 ◽  
Vol 19 (3) ◽  
pp. 308-312
Author(s):  
Judith Jing Wen Wong ◽  
Pål Kristian Selbo
Keyword(s):  
Colon Cancer ◽  
Photodynamic Therapy ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Aldehyde Dehydrogenase ◽  
Therapy Resistance ◽  
Colon Cancer Cells ◽  
Aldh Activity ◽  
Aldehyde Dehydrogenases ◽  
Aldehyde Dehydrogenase Activity

Overexpression of Aldehyde Dehydrogenases (ALDH) has been linked to cancer therapy resistance. Here we show that high ALDH activity do not cause resistance against photodynamic therapy using the PCI-photosensitizer TPCS2a/fimaporfin.

Cinnamaldehyde Enhances the Sensitivity of Gastric Cancer Cells to Oxaliplatin by Regulating the PI3K/AKT Pathway

2021 ◽  
Vol 19 (4) ◽  
pp. 427-431
Author(s):  
Li Wang ◽  
Rui Li ◽  
Hui Yang ◽  
Qian Zhang ◽  
Yan Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Therapeutic Agent ◽  
Akt Pathway ◽  
Drug Resistant ◽  
Inhibitory Effects ◽  
Gastric Cancer Cells ◽  
Bioactive Component ◽  
Cancer Types ◽  
Promising Therapeutic Agent

Gastric cancer is the second leading cause of all cancer-related deaths. While chemotherapy is still the main treatment option for patients with advanced gastric cancer, it at times leads to drug resistance and treatment failure. Therefore, there is an urgent need for better pharmacotherapeutics. Cinnamaldehyde is a bioactive component of cinnamon that has been reported to exhibit a variety of biological functions, including antitumor activity with a variety of cancer types. However, its possible effect on gastric cancer remains to be explored. Herein, we have successfully constructed oxaliplatin-resistant gastric cancer cells and shown that cinnamaldehyde could enhance the inhibitory effects of oxaliplatin on cell viability, and stimulate apoptosis in gastric cancer cells. We further found that cinnamaldehyde could regulate PI3K/AKT pathway, and further enhance the sensitivity of gastric cancer cells to oxaliplatin. Therefore, cinnamaldehyde could serve as a promising therapeutic agent for drug resistant gastric cancer.

Effect of Nano-Platinum on Proliferation and Apoptosis of Non-Small Cell Lung Cancer Cells via P53 Pathway

2021 ◽  
Vol 21 (2) ◽  
pp. 903-908
Author(s):  
Yiqun Liu ◽  
Fangjuan Hu ◽  
Long Zhao
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Cisplatin Resistance ◽  
A549 Cells ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Inhibition Rate ◽  
Small Cell Lung

This paper studies the non-small cell lung cancer with interventional treatment of polyethylene imine-coated platinum nanoclusters. The relationship between the inhibition of non-small cell lung cancer cell proliferation, apoptosis, and the expression of its related apoptotic protein p53. Apoptosis experiments were applied was used to detect the effect of nanoplatin on A549 cells. Western blot was used to detect the expression of p53 protein in A549 cells after nanoplatin treatment. We co-cultured nanoplatin with cells for 4 hours and performed nuclear staining. Observed by laser confocal microscopy, we found that nanoplatin can enter the nucleus and cytoplasm of non-small cell lung cancer A549 cells, and the phenomenon of drug entering the nucleus is very obvious. Treatment of non-small cell lung cancer with A549 cells at different concentrations of nanoplatin for 24 hours, with the increase of the concentration, the proliferation inhibition rate of non-small cell lung cancer gradually increased. Treatment of cisplatin-resistant non-small cell lung cancer cells with different concentrations of nanoplatin for 24 hours, as the concentration increases, the proliferation inhibition rate of non-small cell lung cancer gradually increases. After treatment of A549 cells with different concentrations of nanoplatin for 24 hours, the apoptosis rate of A549 cells gradually increased with the increase of drug concentration. Finally, we conclude that nanoplatin has not only inhibitory and pro-apoptotic effects on non-small cell lung cancer cells, but also fluorescent labeling. Compared with cisplatin, nanoplatin can significantly inhibit the proliferation of non-small cell lung cancer cells and overcome its cisplatin resistance. The p53-related signaling pathway may participate in the process of apoptosis and reverse the process of cisplatin resistance, but the specific mechanism and whether there are other signaling pathways involved Further research is needed.

Inhibitory effects of Actinidia Chinensis planch root extracts (acRoots) on human lung cancer cells through retinoic acid receptor beta

2017 ◽  
Vol 5 (1) ◽  
Author(s):  
Lingyan Wang ◽  
Jiayun Hou ◽  
Minghuan Zheng ◽  
Lin Shi
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Human Lung ◽  
Retinoic Acid Receptor ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Inhibitory Effects ◽  
The Core ◽  
Human Lung Cancer Cells ◽  
Receptor Beta

Actinidia Chinensis Planch roots (acRoots) are used to treat many cancers, although the anti-tumor mechanism by which acRoots inhibit cancer cell growth remains unclear. The present study aims at investigating inhibitory effects of acRoots on human lung cancer cells and potential mechanisms. Our data demonstrate that the inhibitory effects of acRoots on lung cancer cells depend on genetic backgrounds and phenotypes of cells. We furthermore found the expression of metabolism-associated gene profiles varied between acRoots-hypersensitive (H460) or hyposensitive lung cancer cells (H1299) after screening lung cancer cells with different genetic backgrounds. We selected retinoic acid receptor beta (RARB) as the core target within metabolism-associated core gene networks and evaluated RARB changes and roles in cells treated with acRoots at different concentrations and timeframes. Hypersensitive cancer cells with the deletion of RARB expression did not response to the treatment with acRoots, while RARB deletion did not change effects of acRoots on hyposensitive cells. Thus, it seems that RARB as the core target within metabolism-associated networks plays important roles in the regulation of lung cancer cell sensitivity to acRoots.

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