4.5 Article

Pinostrobin suppresses the proliferation of lung carcinoma cells by abrogating the cell cycle progression through the inhibition of Notch signaling pathway

期刊

SOUTH AFRICAN JOURNAL OF BOTANY
卷 151, 期 -, 页码 614-622

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ELSEVIER
DOI: 10.1016/j.sajb.2022.08.030

关键词

Pinostrobin; Anticancer; Lung cancer; Apoptosis; Notch signaling

资金

  1. Research Support- ing Project [RSP-2021/352]
  2. King Saud University, Riyadh, King- dom of Saudi Arabia

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The study found that Pinostrobin (PN) can induce apoptosis in human lung cancer A549 cells and achieve this through mechanisms such as reactive oxygen species generation, activation of apoptotic regulators, cell cycle arrest, and downregulation of the Notch pathway.
Pinostrobin (PN) is a dietary bioflavonoid naturally found in numerous medicinal plants. Even though the anticancer potential of flavonoids has been studied; however the molecular targets and the exact mechanism behind their apoptosis-inducing actions are not yet fully elucidated. The present study was aimed to investigate if PN could induce apoptosis in lung cancer A549 cells of human origin. PN reduced the proliferation of A549 cells in a dose-dependent manner. Induction of apoptosis was observed in PN-treated lung cancer cells as evident by DNA fragmentation and Annexin V positive cells. The PN induced reactive oxygen species (ROS) generation in A549 cells, leading to activation of key regulators of apoptosis such as Bax, Bad and Bcl2 as well as release of cytochrome c, and activation of the caspase cascade including caspase-9 and -3. Enhanced loss of Dcm, cytochrome c release and cleavage of caspase-3 & -9 strongly corroborated our findings. Furthermore, PN treatment of lung cancer cells arrested the cell cycle in G0/G1 phase, inhibited constitutive expression of Cyclin D1and CDK4 and induced the mRNA levels of p21Cip1. A dose-dependent decreased expression of Notch-1, Jagged-1 and Hes-1 were noted in PN treated A549 cells. These findings demonstrated that PN suppressed the growth of A549 cells via downregulating the Notch pathway. Thus, subsequent studies focusing on molecular mechanism of PN can pave path for anticancer drug design.(c) 2022 SAAB. Published by Elsevier B.V. All rights reserved.

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