Novel pyrimidinic selenourea induces DNA damage, cell cycle arrest, and apoptosis in human breast carcinoma

Barbosa, Flavio A. R.; Siminski, Tâmila; Canto, Rômulo Faria Santos; Almeida, Gabriela M.; Mota, Nádia S.R.S.; Ourique, Fabiana; Pedrosa, Rozangela Curi; Braga, Antônio L.

doi:10.1016/j.ejmech.2018.06.026

Cited by 41 publications

(26 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well-known that the proliferation of cancer cells is inhibited by anticancer compounds through the induction of cell cycle arrest and/or apoptosis ( Barbosa et al, 2018 , Kumar at al., 2018 , Fei et al, 2019 ). To study the growth inhibition mechanism of the MCF7 human breast cancer cell line by 1 , a cell cycle arrest kit was utilized for measuring the distribution of the cell phases through propidium iodide (PI) staining with flow cytometry ( Fig.…”

Section: Resultsmentioning

confidence: 99%

β-Carboline copper complex as a potential mitochondrial-targeted anticancer chemotherapeutic agent: Favorable attenuation of human breast cancer MCF7 cells via apoptosis

Khan

Usman

et al. 2020

Saudi Journal of Biological Sciences

View full text Add to dashboard Cite

The development of preferentially selective cancer chemotherapeutics is a new trend in drug research. Thus, we designed and synthesized novel ternary complexes, [Cu(tryp)(Hnor) 2 (DMSO)]NO 3 ( 1) and [Zn(tryp)(Hnor) 2 (DMSO)]NO 3 (2) (tryp = DL-Tryptophane; Hnor = Norharmane, β-carboline; DMSO = Dimethyl sulfoxide), characterized with elemental analysis, FTIR, UV–vis, FL, NMR, ESI-MS, and molar conductivity. Furthermore, the TD-DFT studies with UV–vis and FTIR validated the proposed structures of 1 and 2 . Moreover, we evaluated the HOMO-LUMO energy gap and found that 1 has a smaller energy gap than 2 . Then, 1 and 2 were assessed for anticancer chemotherapeutic potential against cancer cell lines MCF7 (human breast cancer) and HepG2 (human liver hepatocellular carcinoma) as well as the non-tumorigenic HEK293 (human embryonic kidney) cells. The MTT assay illustrated the preferentially cytotoxic behavior of 1 when compared with that of 2 and cisplatin (standard drug) against MCF7 cells. Moreover, 1 was exposed to MCF7 cells, and the results indicated the arrest of the G2/M phases, which followed the apoptotic pathway predominantly. Generation of ROS, GSH depletion, and elevation in LPO validated the redox changes prompted by 1 . These studies establish the great potential of 1 as a candidate for anticancer therapeutics.

show abstract

Section: Resultsmentioning

confidence: 99%

β-Carboline copper complex as a potential mitochondrial-targeted anticancer chemotherapeutic agent: Favorable attenuation of human breast cancer MCF7 cells via apoptosis

Khan

Usman

et al. 2020

Saudi Journal of Biological Sciences

View full text Add to dashboard Cite

show abstract

“…The DNA damage response (DDR) is one of the molecular events leading to cell apoptosis. Numerous anti-cancer agents have been demonstrated to induce DNA double-strand breaks in cancer cells to promote the cell apoptosis (Barbosa et al, 2018;Seah et al, 2018). In response to DNA damage, the ATM will be activated and phosphorylate the downstream substrates such as histone H2AX, cell cycle checkpoint kinases Chk-1 and Chk-2.…”

Section: Discussionmentioning

confidence: 99%

Eupalinolide J induces apoptosis, cell cycle arrest, mitochondrial membrane potential disruption and DNA damage in human prostate cancer cells

Dai

et al. 2020

J. Toxicol. Sci.

View full text Add to dashboard Cite

-Eupalinolide J (EJ) is a new sesquiterpene lactone isolated from Eupatorium lindleyanum DC. In the present study, we investigated the anti-cancer activity of EJ on cell proliferation in human prostate cancer cells. The MTT results indicated that EJ showed marked anti-proliferative activity in PC-3 and DU-145 cells in a dose-and time-dependent manner. DAPI staining analysis demonstrated that this effect was mediated by induction of cell apoptosis. Flow cytometric analysis indicated a significant increase in apoptotic cells, cell cycle arrest at G0/G1 phase and disruption of mitochondrial membrane potential (MMP) after EJ treatment. Meanwhile, the activation of caspase-3 and caspase-9 was visibly observed. Furthermore, our results demonstrated that the expression levels of γH2AX, p-Chk1 and p-Chk2 were significantly up-regulated, suggesting the induction of DNA damage responses in EJ-treated prostate cancer cells. The above results indicated that EJ exhibited effective anti-cancer activity in vitro. It could be a promising candidate agent for the clinical treatment of prostate cancer.

show abstract

“…Chen and collaborators [ 20 ] reported that the action mechanisms of chemically innovative organic compounds containing selenium in cancer therapy involve mitochondria-mediated pathway induced by ROS, activation of the AMPK pathway, and cell death by necrocytosis, autophagy, mitochondria, or death receptor-mediated pathways. Moreover, the toxicological and chemotherapeutic effects in which organoselenium compounds are involved also include inhibition of thioredoxin reductase [ 21 ], DNA damage, apoptosis, and cell cycle arrest [ 22 ] [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

IP-Se-06, a Selenylated Imidazo[1,2-a]pyridine, Modulates Intracellular Redox State and Causes Akt/mTOR/HIF-1α and MAPK Signaling Inhibition, Promoting Antiproliferative Effect and Apoptosis in Glioblastoma Cells

Santos

Rafique

Saba

et al. 2022

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is a notably lethal brain tumor associated with high proliferation rate and therapeutic resistance, while currently effective treatment options are still lacking. Imidazo[1,2-a]pyridine derivatives and organoselenium compounds are largely used in medicinal chemistry and drug development. This study is aimed at further investigating the antitumor mechanism of IP-Se-06 (3-((2-methoxyphenyl)selanyl)-7-methyl-2-phenylimidazol[1,2-a]pyridine), a selenylated imidazo[1,2-a]pyridine derivative in glioblastoma cells. IP-Se-06 exhibited high cytotoxicity against A172 cells ( I C 50 = 1.8 μ M ) and selectivity for this glioblastoma cell. The IP-Se-06 compound has pharmacological properties verified in its ADMET profile, especially related to blood-brain barrier (BBB) permeability. At low concentration (1 μM), IP-Se-06 induced intracellular redox state modulation with depletion of TrxR and GSH levels as well as inhibition of NRF2 protein. IP-Se-06 also decreased mitochondrial membrane potential, induced cytochrome c release, and chromatin condensation. Furthermore, IP-Se-06 induced apoptosis by decreasing levels of Bcl-xL while increasing levels of γ-H2AX and p53 proteins. Treatment with IP-Se-06 induced cell cycle arrest and showed antiproliferative effect by inhibition of Akt/mTOR/HIF-1α and ERK 1/2 signaling pathways. In addition, IP-Se-06 displayed significant inhibition of p38 MAPK and p-p38, leading to inhibition of inflammasome complex proteins (NLRP3 and caspase-1) in glioblastoma cells. These collective findings demonstrated that IP-Se-06 is a bioactive molecule that can be considered a candidate for the development of a novel drug for glioblastoma treatment.

show abstract

Novel pyrimidinic selenourea induces DNA damage, cell cycle arrest, and apoptosis in human breast carcinoma

Cited by 41 publications

References 78 publications

β-Carboline copper complex as a potential mitochondrial-targeted anticancer chemotherapeutic agent: Favorable attenuation of human breast cancer MCF7 cells via apoptosis

β-Carboline copper complex as a potential mitochondrial-targeted anticancer chemotherapeutic agent: Favorable attenuation of human breast cancer MCF7 cells via apoptosis

Eupalinolide J induces apoptosis, cell cycle arrest, mitochondrial membrane potential disruption and DNA damage in human prostate cancer cells

IP-Se-06, a Selenylated Imidazo[1,2-a]pyridine, Modulates Intracellular Redox State and Causes Akt/mTOR/HIF-1α and MAPK Signaling Inhibition, Promoting Antiproliferative Effect and Apoptosis in Glioblastoma Cells

Contact Info

Product

Resources

About