Seco-polyprenylated acylphloroglucinols from Hypericum elodeoides induced cell cycle arrest and apoptosis in MCF-7 cells via oxidative DNA damage

Tian, Wenjing; Zhou, Mei; Qiu, Daren; Chen, Junjie; Liu, Xiangzhong; Li, Jing-Dian; Lin, Ting; Wang, Guanghui; Chen, Haifeng

doi:10.1016/j.bioorg.2022.106088

Cited by 2 publications

(1 citation statement)

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“…Indeed, the cells are blocked in the S phase in the presence of IB42 and IB44 as in the presence of GW6471, whereas the MCF7 cells accumulate in the G2/M phase in the presence of IB66. To induce a cell cycle arrest at the S phase can be compatible with an oxidative DNA damage caused by compounds, as already reported for MCF7 cells [ 37 ]. In parallel, the different cell behaviors in the presence of IB66 warrant in-depth exploration.…”

Section: Discussionmentioning

confidence: 69%

Phenylsulfonimide PPARα Antagonists Enhance Nrf2 Activation and Promote Oxidative Stress-Induced Apoptosis/Pyroptosis in MCF7 Breast Cancer Cells

Gallorini

Valerio

Bruno

et al. 2023

IJMS

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The NF-E2-related factor 2 transcription factor (Nrf2) orchestrates the basal and stress-inducible activation of a vast array of antioxidant genes. A high amount of reactive oxygen species (ROS) promotes carcinogenesis in cells with defective redox-sensitive signaling factors such as Nrf2. In breast cancer (BC), emerging evidence indicates that increased Nrf2 activity enhances cell metastatic potential. An interconnection between peroxisome proliferator-activated receptors (PPARs) and Nrf2 pathways in cancer has been shown. In this light, newly synthesized PPARα antagonists, namely IB42, IB44, and IB66, were tested in the BC cell line MCF7 in parallel with GW6471 as the reference compound. Our results show that the most promising compound of this phenylsulfonimide series (IB66) is able to decrease MCF7 proliferation by blocking cells at the G2/M checkpoint. The underlying mechanism has been investigated, disclosing a caspase 3/Akt-dependent apoptotic/pyroptotic pathway induced by the increased generation of oxidative stress. Moreover, the involvement of Nrf2 and COX2 in IB66-treated MCF7 cell response has been highlighted. The reported data lay the groundwork for the development of alternative targeted therapy involving the Nrf2/PPARα molecular axis, able to overcome BC cell chemoresistance and cause better clinical outcomes, promoting other forms of programmed cell death, such as pyroptosis.

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Section: Discussionmentioning

confidence: 69%