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A1E inhibits proliferation and induces apoptosis in NCI-H460 lung cancer cells via extrinsic and intrinsic pathways

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Abstract

It has been reported that extracts from Asian traditional/medical herbs possess therapeutic agents against cancers, metabolic diseases, inflammatory diseases, and other intractable diseases. In this study, we assessed the molecular mechanisms involved in the anticancer effects of A1E, the extract of Korean medicinal herbs. We examined the role of the cytotoxic and apoptotic pathways in the cancer chemopreventive activity in non-small-cell lung cancer (NSCLC) cell lines NCI-H460 and NCI-H1299. A1E inhibited the proliferation of NCI-H460 more efficiently than NCI-H1299 (p53−/−) cells. The apoptosis was detected by nuclear morphological changes, annexin V-FITC/PI staining, cell cycle analysis, western blot, RT-PCR, and measurement of mitochondrial membrane potential. A1E induced cellular morphological changes and nuclear condensation at 24 h in a dose-dependent manner. A1E also perturbed cell cycle progression at the sub-G1 stage and altered cell cycle regulatory factors in NCI-H460 cells. Furthermore, A1E inhibited the PI3K/Akt and NF-κB survival pathways, and it activated apoptotic intrinsic and extrinsic pathways. A1E increased the expression levels of members of the extrinsic death receptor complex FasL and FADD. In addition, A1E treatment induced cleavage of caspase-8, caspase-9, caspase-3, and poly ADP-ribose polymerase (PARP), whereas the expression levels of Bcl-2 and Bcl-xl were downregulated. A1E induced mitochondrial membrane potential collapse and cytochrome C release. Our results suggest that A1E induces apoptosis via activation of both extrinsic and intrinsic pathways and inhibition of PI3K/Akt survival signaling pathways in NCI-H460 cells. In conclusion, these data demonstrate the potential of A1E as a novel chemotherapeutic agent in NSCLC.

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Abbreviations

NSCLC:

Non-small cell lung cancer

PARP:

Poly (ADP-ribose) polymerase

PI:

Propidium iodide

PI3K:

Phosphatidylinositol 3-kinase

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

HRP:

Horseradish peroxidase

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Acknowledgments

This study was supported by a Grant (B110053) from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea. D.Y. was partially supported by a program (2012-0006686) from the National Research Foundation of Korea (NRF).

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Authors and Affiliations

  1. Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong 1, Gwangjin-gu, Seoul, 143–701, Republic of Korea

    Yesol Bak, Sunyoung Ham & Do-Young Yoon

  2. School of Oriental Medicine, Dongguk University, Siksa dong, Ilsan, Republic of Korea

    O. Baatartsogt & Seung hyun Jung

  3. Graduate School of Bio & Information Technology, Hankyong National University, Ansung, Kyungki-do, Republic of Korea

    Kang-Duk Choi

  4. Banryong Insu Herb Clinic, Nonhyun-dong, Gangnam-ku, Seoul, Republic of Korea

    Tae-Young Han

  5. Sunwun Biophysic, Ansung, Kyungki-do, Republic of Korea

    Il-Young Han

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  1. Yesol Bak
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Correspondence to Do-Young Yoon.

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Bak, Y., Ham, S., Baatartsogt, O. et al. A1E inhibits proliferation and induces apoptosis in NCI-H460 lung cancer cells via extrinsic and intrinsic pathways. Mol Biol Rep 40, 4507–4519 (2013). https://doi.org/10.1007/s11033-013-2544-0

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  • DOI: https://doi.org/10.1007/s11033-013-2544-0

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