Dataset Information

Identification of Novel Artemisinin Hybrids Induce Apoptosis and Ferroptosis in MCF-7 Cells.

ABSTRACT: A series of novel 1,3,4-oxadiazole-artemisinin hybrids have been designed and synthesized. An MTT assay revealed that most of tested hybrids showed more enhanced anti-proliferative activities than artemisinin, among which A8 had the superior potency with IC50 values ranging from 4.07 μM to 9.71 μM against five tested cancer cell lines. Cell colony formation assays showed that A8 could inhibit significantly more cell proliferation than artemisinin and 5-fluorouracil. Further mechanism studies reveal that A8 induces apoptosis and ferroptosis in MCF-7 cells in a dose-dependent manner, and CYPs inhibition assays reveal that A8 has a moderate inhibitory effect on CYP1A2 and CYP3A4 in the human body at 10 μM. The present work indicates that hybrid A8 may merit further investigation as a potential therapeutic agent.

SUBMITTER: Zhong Y

PROVIDER: S-EPMC9779727 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Identification of Novel Artemisinin Hybrids Induce Apoptosis and Ferroptosis in MCF-7 Cells.

Zhong Ye Y Li Zhi-Ning ZN Jiang Xin-Yue XY Tian Xing X Deng Ming-Hui MH Cheng Mao-Sheng MS Yang Hua-Li HL Liu Yang Y

International journal of molecular sciences 20221212 24

A series of novel 1,3,4-oxadiazole-artemisinin hybrids have been designed and synthesized. An MTT assay revealed that most of tested hybrids showed more enhanced anti-proliferative activities than artemisinin, among which A8 had the superior potency with IC<sub>50</sub> values ranging from 4.07 μM to 9.71 μM against five tested cancer cell lines. Cell colony formation assays showed that A8 could inhibit significantly more cell proliferation than artemisinin and 5-fluorouracil. Further mechanism ...[more]

PMID: 36555409

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Project description:The present study aimed to synthesize iron oxide nanoparticles loaded with quinine and alkaloids-rich Cinchona officinalis (Peruvian bark) stem bark extract, and further evaluate their cytotoxic effect and apoptosis mechanisms in MCF-7 breast cancer cells. Nanoparticles were prepared by biological reduction of iron oxide with Cinchona officinalis extract, using the green synthesis method. The nanoparticles were characterized by XRD, FT-IR, and UV-vis spectroscopy and transmission electron microscopy (TEM). In vitro cytotoxicity analyses of Cinchona officinalis extract, ferrous oxide, and Cinchona officinalis extract-loaded iron oxide nanoparticles (CO-NPs) were carried out using the MTT test for 24 h and 48 h. We found that CO-NPs reduced the MCF-7 cell viability with IC50 values of 16.2 and 9 µg/mL in 24 h and 48 h, respectively. In addition, CO-NPs were tested with normal hMSCs to determine their toxicity, and we did not find noticeable cytotoxicity. Confocal fluorescent microscopy revealed that CO-NPs efficiently increased the nuclear condensation and chromatin damage in propidium iodide staining; meanwhile, there was decreased mitochondrial membrane potential in CO-NPs-treated MCF-7 cells. In addition, AO-EB staining confirmed the late apoptotic and apoptotic morphology of cancer cells. Further gene expression analysis confirmed that the upregulation of tumor suppressors, Cdkn1A, Prb, and p53 was significantly increased, and inflammatory traits such as TNF-α and Nf-κb were increased in cancer cells treated with CO-NPs. Apoptotic stimulators such as Bax and caspase-3 expression were highly significantly increased, while mdm-2 and Bcl-2 were significantly decreased. Overall, the enhanced cytotoxic potential of the Cinchona officianlis stem bark extract loaded CO-NPs versus free Cinchona officianlis extract might be due to the functional stabilization of bioactive compounds, such as alkaloids, quinine, flavonoids, phenolics, etc., into the iron oxide, providing bioavailability and internalization of cinchona metabolites intracellularly.

Dataset Information

Identification of Novel Artemisinin Hybrids Induce Apoptosis and Ferroptosis in MCF-7 Cells.

Publications

Identification of Novel Artemisinin Hybrids Induce Apoptosis and Ferroptosis in MCF-7 Cells.

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