N-Propargylic β-enaminones in breast cancer cells: Cytotoxicity, apoptosis, and cell cycle analyses

Ilhan, Suleyman
Atmaca, Harika
Yılmaz, Elif Serel
Zora, Metin
Breast cancer is one of the most common cancers worldwide and the discovery of new cytotoxic agents is needed. Enaminones are regarded to be a significant structural motif that is found in a variety of pharmacologically active compounds however the number of studies investigating the anticancer activities of N-propargylic β-enaminones (NPEs) is limited. Herein we investigated the potential cytotoxic and apoptotic effects of 23 different NPEs (1-23) on human breast cancer cells. Cytotoxicity was evaluated via MTT assay. Apoptotic cell death and cell cycle distributions were investigated by flow cytometry. CM-H2DCFDA dye was used to evaluate cellular ROS levels. Expression levels of Bcl-2, Bax, p21, and Cyclin D1 were measured by quantitative real-time PCR. ADME properties were calculated using the ADMET 2.0 tool. NPEs 4, 9, 16, and 21 showed selective cytotoxic activity against breast cancer cells with SI values >2. NPEs induced apoptosis and caused significant changes in Bcl-2 and Bax mRNA levels. The cell cycle was arrested at the G0/G1 phase and levels of p21 and Cyclin D1 were upregulated in both breast cancer cells. ROS levels were significantly increased by NPEs, suggesting that the cytotoxic and apoptotic effects of NPEs were mediated by ROS. ADME analysis revealed that NPEs showed favorable distributions in both breast cancer cell lines, meaning good lipophilicity values, low unfractionated values, and high bioavailability. Therefore, these potential anticancer compounds should be further validated by in vivo studies for their appropriate function in human health with a safety profile, and a comprehensive drug interaction study should be performed.
Journal of Biochemical and Molecular Toxicology


Cell-surface interactions in a breast cancer model
Antmen, Ezgi; Hasırcı, Vasıf Nejat; Demirci, Utkan; Department of Biotechnology (2017)
Breast cancer, is one of the most commonly diagnosed cancers, has a high mortality rate. One in every eight women (12.3%) develops breast cancer at some stage of their lives and this is the cause of about 15% of cancer deaths in women and 3% of total deaths. It is therefore important to study the behavior of breast cancer cells. Measurement of the mechanical properties of cancer cells leads to new insights such as that cancer cells are softer than healthy cells. Also, metastatic cancer cells were found to b...
Reversal of breast cancer resistance protein mediated multidrug resistance in MCF7 breast adenocarcinoma cell line
Urfalı, Çağrı; Gündüz, Ufuk; Department of Biology (2011)
Resistance to various chemotherapeutic agents is a major problem in success of cancer chemotherapy. One of the primary reasons of development of multidrug resistance (MDR) is the overexpression of ATP binding cassette (ABC) transporter proteins. Breast cancer resistance protein (BCRP) belongs to ABC transporter family and encoded by ABCG2 gene. BCRP is mainly expressed in MDR1 (P-glycoprotein) lacking breast cancer cells. Overexpression of BCRP leads to efflux of chemotherapeutic agents at higher rates, the...
Nuclear Deformability of Breast Cells Analyzed from Patients with Malignant and Benign Breast Diseases
Antmen, Ezgi; Ermiş Şen, Menekşe; Kuren, Ozgur; Beksac, Kemal; Irkkan, Cigdem; HASIRCI, Vasıf Nejat (2023-03-13)
Breast cancer is a heterogeneous and dynamic disease, in which cancer cells are highly responsive to alterations in the microenvironment. Today, conventional methods of detecting cancer give a rather static image of the condition of the disease, so dynamic properties such as invasiveness and metastasis are difficult to capture. In this study, conventional molecular-level evaluations of the patients with breast adenocarcinoma were combined with in vitro methods on micropatterned poly(methyl methacrylate) (PM...
Synthesis of novel indole-isoxazole hybrids and evaluation of their cytotoxic activities on hepatocellular carcinoma cell lines
Hawash, Mohammed; Kahraman, Deniz Cansen; Ergun, Sezen Guntekin; Cetin-Atalay, Rengul; BAYTAŞ, SULTAN (2021-12-01)
Background Liver cancer is predicted to be the sixth most diagnosed cancer globally and fourth leading cause of cancer deaths. In this study, a series of indole-3-isoxazole-5-carboxamide derivatives were designed, synthesized, and evaluated for their anticancer activities. The chemical structures of these of final compounds and intermediates were characterized by using IR, HRMS, H-1-NMR and C-13-NMR spectroscopy and element analysis. Results The cytotoxic activity was performed against Huh7, MCF7 and HCT116...
Design for positive breast self-examination experience: an investigation into mobile health apps
Karadeniz Küçük, Aylin; Şener Pedgley, Bahar; Department of Industrial Design (2021-5)
Breast cancer is one of the most common cancer types among women, responsible for approximately 627,000 deaths globally in 2018. There are various screening methods to detect cancer early, and experts suggest that women should perform breast self-examination (BSE) once a month. Unfortunately, most women fail to do so even if they are aware of the risks and the importance of screening methods. Moreover, developments in technology provide people to manage their own health in their own environments with variou...
Citation Formats
S. Ilhan, H. Atmaca, E. S. Yılmaz, E. YILDIZ, and M. Zora, “N-Propargylic β-enaminones in breast cancer cells: Cytotoxicity, apoptosis, and cell cycle analyses,” Journal of Biochemical and Molecular Toxicology, pp. 0–0, 2023, Accessed: 00, 2023. [Online]. Available: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85146355086&origin=inward.