Design, synthesis and biological evaluation of a new series of arylidene indanones as small molecules for targeted therapy of non-small cell lung carcinoma and prostate cancer

Altıntop, Mehlika Dilek; Özdemır, Ahmet; Temel, Halide Edip; Cevizlidere, Bahar Demir; Sever, Belgin; Kaplancıklı, Zafer Asım; Çiftçi, Gülşen Akalın

doi:10.1016/j.ejmech.2022.114851

Cited by 9 publications

(3 citation statements)

References 75 publications

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“…Moreover, apoptosis is involved in tumor formation and cancer therapy and is regarded as a main defense mechanism against tumorigenesis [ 29 ]. Numerous anticancer agents exert their inhibitory effects by triggering apoptosis [ 30 , 31 , 32 ]. It has been shown that two major apoptotic pathways are capable of initiating apoptosis: the mitochondrial-mediated intrinsic pathway and the death receptor-mediated extrinsic pathway [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Compound 275# Induces Mitochondria-Mediated Apoptosis and Autophagy Initiation in Colorectal Cancer Cells through an Accumulation of Intracellular ROS

Yang

et al. 2023

Molecules

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Colorectal cancer (CRC) is the most common intestinal malignancy, and nearly 70% of patients with this cancer develop metastatic disease. In the present study, we synthesized a novel compound, termed N-(3-(5,7-dimethylbenzo [d]oxazol-2-yl)phenyl)-5-nitrofuran-2-carboxamide (compound 275#), and found that it exhibits antiproliferative capability in suppressing the proliferation and growth of CRC cell lines. Furthermore, compound 275# triggered caspase 3-mediated intrinsic apoptosis of mitochondria and autophagy initiation. An investigation of the molecular mechanisms demonstrated that compound 275# induced intrinsic apoptosis, and autophagy initiation was largely mediated by increasing the levels of the intracellular accumulation of reactive oxygen species (ROS) in CRC cells. Taken together, these data suggest that ROS accumulation after treatment with compound 275# leads to mitochondria-mediated apoptosis and autophagy activation, highlighting the potential of compound 275# as a novel therapeutic agent for the treatment of CRC.

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Section: Discussionmentioning

confidence: 99%

Compound 275# Induces Mitochondria-Mediated Apoptosis and Autophagy Initiation in Colorectal Cancer Cells through an Accumulation of Intracellular ROS

Yang

et al. 2023

Molecules

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“…These three transporter systems have drug specificity and carry a number of structural compounds that cause a reduced accumulation of drugs inside the cells and, consequently, a decrease in drug effectiveness. 18,19 P-gp is the first identified and most characterized MDR1 transporter protein and is recognized as an important target protein in cancer treatment. High expression of P-gp in cancer cells was found in connection with a decrease in the chemotherapeutic effect and a decrease in its positive clinical results.…”

Section: Significance Statementmentioning

confidence: 99%

“…Among these members; P‐glycoprotein (P‐gp; also called MDR1, Decb1), MDR1‐related protein (MRP1) and breast cancer resistance proteins (BCRP1) have been characterized as MDR proteins. These three transporter systems have drug specificity and carry a number of structural compounds that cause a reduced accumulation of drugs inside the cells and, consequently, a decrease in drug effectiveness 18,19 …”

Section: Introductionmentioning

confidence: 99%

Establishment, culture and characterization of gemcitabine hydrochloride‐resistant human non‐small cell lung carcinoma cell line derived cancer stem cells

Demir Cevizlidere,

Uysal,

Avci

et al. 2024

Cell Biochemistry & Function

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Due to their high expression profile of multi‐drug resistance genes, cancer stem cells (CSCs) are the main source of drug resistance. The aim of this study was to establish a gemcitabine‐hydrochloride‐resistant (rt) human non‐small cell lung cancer (hNSCLC) cell line and their CSC line to be used as disease models in various cancer studies. In the first phase of study, a gemcitabine hydrochloride‐rt hNSCLC line cells was produced by making them rt through periodic exposure to gemcitabine hydrochloride. This acquired gemcitabine‐hydrochloride‐rt hNSCLC cell line was characterized for resistance. Subsequently, a CSC population with a CD326 + CD133 + CD44+ phenotypes was immunoselectively isolated from gemcitabine hydrochloride‐rt hNSCLCs purified from a single cell by colony forming technology. This rt CSC line was characterized for both resistance and stemness. Rt and non‐rt CSCs were analyzed and compared with each other in terms of immunophenotyping the expression profiles of ALDH1, CD90, ABCG2, CD44 and MDR1, which are CSC specific markers, of demonstrating mitotic capacity with growth curve analysis and of their ability to form tumor spheroids in three different 3D cultures. The results of this study demonstrated for the first time the successful generation of both gemcitabine‐hydrochloride‐rt hNSCLC cells and CSCs derived from gemcitabine‐hydrochloride‐rt hNSCLC cells. It was also shown that isolated and characterized rt CSCs could proliferate and form tumor spheres in vitro using three different 3D in vitro techniques. It was shown that the cell surface markers CD326, CD133 and CD44 can serve as an antibody panel for CSCs.

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Discovery of dolutegravir-1,2,3-triazole derivatives against prostate cancer via inducing DNA damage

Zhou,

Hou,

et al. 2023

Bioorganic Chemistry

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Design, synthesis and biological evaluation of a new series of arylidene indanones as small molecules for targeted therapy of non-small cell lung carcinoma and prostate cancer

Cited by 9 publications

References 75 publications

Compound 275# Induces Mitochondria-Mediated Apoptosis and Autophagy Initiation in Colorectal Cancer Cells through an Accumulation of Intracellular ROS

Compound 275# Induces Mitochondria-Mediated Apoptosis and Autophagy Initiation in Colorectal Cancer Cells through an Accumulation of Intracellular ROS

Establishment, culture and characterization of gemcitabine hydrochloride‐resistant human non‐small cell lung carcinoma cell line derived cancer stem cells

Discovery of dolutegravir-1,2,3-triazole derivatives against prostate cancer via inducing DNA damage

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