Isokotomolide A, a new butanolide extracted from the leaves of Cinnamomum kotoense, arrests cell cycle progression and induces apoptosis through the induction of p53/p21 and the initiation of mitochondrial system in human non-small cell lung cancer A549 cells

Chen, Chung‐Yi; Hsu, Ya‐Ling; Chen, Yinyi; Hung, Jen‐Yu; Huang, Ming‐Shyan; Kuo, Po‐Lin

doi:10.1016/j.ejphar.2007.07.028

Cited by 55 publications

(17 citation statements)

References 25 publications

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“…LYG-202, a new flavonoid with a piperazine substitution, which shares the structural similarity with Wogonin, has an antitumor activity in a dose-dependent manner in vivo [36,37]. In the present study, we demonstrated that LYG-202 exerts the antitumor effect by inducing apoptosis and G1/S cell cycle arrest in human breast cancer cells.…”

Section: Discussionmentioning

confidence: 63%

LYG-202 exerts antitumor effect on PI3K/Akt signaling pathway in human breast cancer cells

et al. 2015

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In this study, we aimed to investigate the antitumor effect of LYG-202, a newly synthesized piperazine-substituted derivative of flavonoid on human breast cancer cells and illustrate the potential mechanisms. LYG-202 induced apoptosis in MCF-7, MDA-MB-231 and MDA-MB-435 cells. LYG-202 triggered the activation of mitochondrial apoptotic pathway through multiple steps: increasing Bax/Bcl-2 ratio, decreasing mitochondrial membrane potential (ΔΨ(m)), activating caspase-9 and caspase-3, inducing cleavage of poly(ADP-ribose) polymerase, cytochrome c release and apoptosis-inducing factor translocation. Furthermore, LYG-202 inhibited cell cycle progression at the G1/S transition via targeting Cyclin D, CDK4 and p21(Waf1/Cip1). Additionally, LYG-202 increased the generation of intracellular ROS. N-Acetyl cysteine, an antioxidant, reversed LYG-202-induced apoptosis suggesting that LYG-202 induces apoptosis by accelerating ROS generation. Further, we found that LYG-202 deactivated the PI3K/Akt pathway, activated Bad phosphorylation, increased Cyclin D and Bcl-xL expression, and inhibited NF-κB nuclear translocation. Activation of PI3K/Akt pathway by IGF-1 attenuated LYG-202-induced apoptosis and cell cycle arrest. Our in vivo study showed that LYG-202 exhibited a potential antitumor effect in nude mice inoculated with MCF-7 tumor through similar mechanisms identified in cultured cells. In summary, our results demonstrated that LYG-202 induced apoptosis and cell cycle arrest via targeting PI3K/Akt pathway, indicating that LYG-202 is a potential anticancer agent for breast cancer.

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Section: Discussionmentioning

confidence: 63%

LYG-202 exerts antitumor effect on PI3K/Akt signaling pathway in human breast cancer cells

et al. 2015

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“…Molecular mechanisms contributing to NSCLC pathogenesis have been extensively investigated. Mutant vital genes and dysregulating cell signaling pathways, including EGFR [27, 36], HER 2 [37], EML 4 -ALK [38], RAS/MEK [39], PI3K/Akt/mTOR [40], and P53/P21 [41–43] have been found to play pivotal roles in NSCLC carcinogenesis and progression. Among them, the activated p53/p21 signal is well established as a critical determinant in controlling both cell-cycle arrest and apoptosis [25, 44].…”

Section: Discussionmentioning

confidence: 99%

By downregulating Ku80, hsa-miR-526b suppresses non-small cell lung cancer

Zhang

et al. 2014

Oncotarget

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Ku80 is involved in DNA double-strand breaks (DSBs) repair. Ku80 is overexpressed in lung cancer tissues, yet, molecular mechanisms have not been examined. We identified that miRNA, hsa-miR-526b, is bound to the 3′-UTR of Ku80 mRNA, thus decreasing Ku80 expression in NSCLC cells. Hsa-miR-526b was downregulated in NSCLC tissues compared with corresponding non-tumorous tissues, and its expression was inversely correlated with Ku80 upregulation. Overexpression of Ku80 and downregulation of hsa-miR-526b were associated with poor clinical outcomes of NSCLC patients. Hsa-miR-526b suppressed NSCLC cell proliferation, clonogenicity, and induced cell cycle arrest and apoptosis. Hsa-miR-526b inhibited xenografts and orthotopic lung tumor growth. Further, Ku80 knockdown in NSCLC cells suppressed tumor properties in vitro and in vivo similar to hsa-miR-526b overexpression. In agreement, Ku80 restoration partially reversed cell cycle arrest and apoptosis induced by hsa-miR-526b in NSCLC cells in vitro and in vivo. In addition, hsa-miR-526b overexpression or Ku80 knockdown increased p53 and p21CIP1/WAF1 expression. These findings reveal that hsa-miR-526b is a potential target in cancer therapy.

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“…Activation of caspases cascade and subsequent cleavage of its downstream targets are considered the biochemical hallmark of apoptotic cell death (Blank and Shiloh, 2007;Chen et al, 2007). The death receptor pathway (extrinsic pathway) is activated by ligand-bound death receptors of the tumor necrosis factor superfamily, resulting in the activation of initiator caspases (caspase 8), and ϰ subsequent activation of the downstream effectors (caspase 3, 6 and 7) (Nagata, 1999).…”

Section: Introductionmentioning

confidence: 99%

III-10, a newly synthesized flavonoid, induces cell apoptosis with the involvement of reactive oxygen species-mitochondria pathway in human hepatocellular carcinoma cells

Dai

Yin

Zhao

et al. 2015

European Journal of Pharmacology

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Isokotomolide A, a new butanolide extracted from the leaves of Cinnamomum kotoense, arrests cell cycle progression and induces apoptosis through the induction of p53/p21 and the initiation of mitochondrial system in human non-small cell lung cancer A549 cells

Cited by 55 publications

References 25 publications

LYG-202 exerts antitumor effect on PI3K/Akt signaling pathway in human breast cancer cells

LYG-202 exerts antitumor effect on PI3K/Akt signaling pathway in human breast cancer cells

By downregulating Ku80, hsa-miR-526b suppresses non-small cell lung cancer

III-10, a newly synthesized flavonoid, induces cell apoptosis with the involvement of reactive oxygen species-mitochondria pathway in human hepatocellular carcinoma cells

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