Apoptosis induction by 13-acetoxyrolandrolide through the mitochondrial intrinsic pathway

Phytotherapy Research : PTR
Ulyana Muñoz AcuñaEsperanza J Carcache de Blanco

Abstract

The aim of this study was to evaluate the mechanisms of cytotoxicity of the sesquiterpene lactone 13-acetoxyrolandrolide, a nuclear factor kappa B (NF-κB) inhibitor that was previously isolated from Rolandra fruticosa. The effects associated with the inhibition of the NF-κB pathway included dose-dependent inhibition of the NF-κB subunit p65 (RelA) and inhibition of upstream mediators IKKβ and oncogenic Kirsten rat sarcoma (K-Ras). The inhibitory concentration of 13-acetoxyrolandrolide on K-Ras was 7.7 µM. The downstream effects of the inhibition of NF-κB activation were also investigated in vitro. After 24 h of treatment with 13-acetoxyrolandrolide, the mitochondrial transmembrane potential was depolarized in human colon cancer (HT-29) cells. The mitochondrial oxidative phosphorylation was also negatively affected, and reduced levels of nicotinamine adenine dinucleotide phosphate (NAD(P)H) were detected after 2 h of 13-acetoxyrolandrolide exposure. Furthermore, the expression of the pro-apoptotic protein caspase-3 increased in a concentration-dependent manner. Cell flow cytometry showed that 13-acetoxyrolandrolide induced cell cycle arrest at G1 , indicating that the treated cells had undergone caspase-3-mediated apoptosis, ind...Continue Reading

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Citations

Jul 27, 2017·Phytotherapy Research : PTR·Yuan XiangTao Yanduo
May 29, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Haixia WangHong-Ping Zhao
Sep 1, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Hanaa H AhmedMohamed B Shalaby

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis