Boehmenan, a Lignan From the Chinese Medicinal Plant , Inhibits A431 Cell Growth via Blocking p70S6/S6 Kinase Pathway

Autor: Li-Long Pan PhD, Xi-Ling Wang PhD, Xiao-Ling Luo MS, Si-Yu Liu PhD, Peng Xu MS, Jin-Feng Hu PhD, Xin-Hua Liu PhD
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Integrative Cancer Therapies, Vol 16 (2017)
Druh dokumentu: article
ISSN: 1534-7354
1552-695X
15347354
DOI: 10.1177/1534735416669803
Popis: Previously, we have shown that boehmenan, a natural product isolated from the dried stem of Caulis clematidis armandii , exhibits various biological activities. The current study investigated the effects of boehmenan on the growth of human epidermoid carcinoma A431 cells. Cell viability and 50% inhibiting concentration (IC 50 ) were assessed by CellTiter-Glo luminescent cell viability assay. Cell cycle arrest was measured by flow cytometry. Intracellular reactive oxygen species production and mitochondrial membrane potential (ΔΨ m ) collapse were analyzed by a fluorescence spectrophotometer. The activation of epidermal growth factor receptor signaling pathway was evaluated by Western blot. The results showed that boehmenan significantly inhibited the growth of A431 cells (IC 50 = 1.6 µM) in a concentration- and time-dependent manner. This compound also blocked cell cycle progression at G2/M phase and modulated mitochondrial apoptosis-related proteins, as evidenced by upregulating p21, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase protein levels and by downregulating Bcl-2, pro-caspase-9 levels. In addition, boehmenan also markedly induced intracellular reactive oxygen species production and ΔΨ m depolarization in a concentration-dependent manner. Furthermore, boehmenan-attenuated epidermal growth factor mediated the phosphorylation of signal transducer and activator of transcription 3 (STAT3), p70 ribosomal protein S6 kinase (p70S6)/S6 in a concentration-dependent manner. Taken together, our results suggest that boehmenan-mediated antiproliferative property in A431 cells was mediated partially by modulation of mitochondrial function and inhibition of STAT3 and p70S6 signal pathways.
Databáze: Directory of Open Access Journals
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