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http://dx.doi.org/10.5352/JLS.2016.26.8.887

The Extract from Artemisia annua Linné. Induces p53-independent Apoptosis through Mitochondrial Signaling Pathway in A549 Lung Cancer Cells  

Kim, Bo-Min (Department of Biological Science and Biotechnology, College of Life Science and Nanotechnology, , Hannam University)
Kim, Guen-Tae (Department of Biological Science and Biotechnology, College of Life Science and Nanotechnology, , Hannam University)
Kim, Eun-Ji (Department of Biological Science and Biotechnology, College of Life Science and Nanotechnology, , Hannam University)
Lim, Eun-Gyeong (Department of Biological Science and Biotechnology, College of Life Science and Nanotechnology, , Hannam University)
Kim, Sang-Yong (Department of Food Science & Bio Technology, Shinansan University)
Kim, Young-Min (Department of Biological Science and Biotechnology, College of Life Science and Nanotechnology, , Hannam University)
Publication Information
Journal of Life Science / v.26, no.8, 2016 , pp. 887-894 More about this Journal
Abstract
The extract from Artemisia annuain L.(AAE) is known as a medicinal herb that is effective against cancer. Apoptosis is the process of programmed cell death, and mitochondria are known to play a central role in cell death control. In this study, we evaluated the p53-independent apoptosis of extract of AAE through downregulation of Bcl-2 and the mitochondrial pathway in A549 (lung cancer cells). AAE may exert cancer cell apoptosis through regulating p-Akt, Cox-2, p53 and mitochondria-mediated apoptotic proteins. p-Akt/cox-2 is known to play an important role in cell proliferation and cell survival. The Bcl-2 pro-apoptotic proteins (such as Bax, Bak and Bim) mediate the permeabilization of the mitochondrial outer membrane. Treatment of AAE reduces p-Akt, p-Mdm2, cox-2 and anti-apoptotic proteins (such as Bcl-2), while tumor suppressor p53 and pro-apoptotic proteins. Activation of Bax/Bak releases cytochrome c from mitochondria to the cytosol to activate a caspase. Caspase-3 is the major effector caspase associated with apoptotic pathways. Caspase-3 generally exists in cytoplasm in the form of a pro-enzyme. In the initiation stage of apoptosis, caspase-3 is activated by proteolytic cleavage and activated caspase-3 cleaves poly (ADP-ribose) polymerase (PARP). We treated Pifithrin-α (p53 inhibitor) and Celecoxib (Cox-2 inhibitor) to learn the relationship between the signal transduction of proteins associated with apoptosis. These results suggest that AAE induces apoptosis through a p53-independent pathway in A549.
Keywords
A549 cells; celecoxib; Cox-2; mitochondrial apoptosis; p53;
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1 ACS. 2012. Cancer facts & figures. American cancer society.
2 Ahmedin, J., D, V. M., Freddie, B., Melissa, M. Center., Jacques, F., Elizabeth, W. and David, F. 2011. Global cancer statistics. CA Cancer J. Clin. 61, 69-90.   DOI
3 Bae, O. S., Yoo, Y. M. and Lee, S. G. 2005. Pro-apoptotic effect of mori cortex radicis in A549 lung cancer cells. Kor. J. Orient Physiol. Pathol. 19, 1563-1567.
4 Choi, T. Y., Lee, S. W., Ryu, Y. H., Ban, H. J., Seo, G. H., Kim, Ahn, S. H and Sohn, I. C. 2010. The induction effect of apoptosis in A549 human lung cancer cells by the trichosanthes kirilowii pharmacopuncture solution. Kor. J. Acupunct. 27, 15-23.
5 Deying, Z., Zhe, L. and Zhenzhong, L. 2015. Aqueous extract of huang-lian induces apoptosis in lung cancer cells via p53-mediated mitochondrial apoptosis. Braz. Arch. Biol. Technol. 58, 353-357.   DOI
6 Duriez, P. and Shah, G. 1997. Cleavage of poly (ADP-ribose) polymerase: a sensitive parameter to study cell death. Biochem. Cell Biol. 75, 337-349.   DOI
7 Felicia, D. G. and David, A. O. 1998. p53 status does not determine outcome of E1B 55-kilodaltonmutant adenovirus lytic infection. ASM 72, 9479-9490.
8 Gottlieb, E., Armour, S. M., Harris, M. H. and Thompson, C. B. 2003. Mitochondrial membrane potential regulates matrix configuration and cytochrome c release during apoptosis. Cell Death Differ. 10, 709-717.   DOI
9 Jorge, F. S. F., Devanand, L. L., Tomikazu, S. and Arne, H. 2010. Flavonoids from artemisia annua L. as antioxidants and their potential synergism with artemisinin against malaria and cancer. MDPI 15, 3135-3170.
10 Jung, C. R., Lim, J. H., Choi, Y. J, Kim, D. G. Kang, K. J., Noh, S. M. and Im, D. S. 2010. Enigma negatively regulates p53 through MDM2 and promotes tumor cell survival in mice. J. Clin. Invest. 120, 4493-4506.   DOI
11 Park, H. J., Jin, S. J., Oh, Y. N., Kim, B. W. and Kwon, H. J. 2015. Induction of apoptosis by methanol extract of endlicheria anomala in human lung and liver cancer cells. J. Life Sci. 25, 441-449.   DOI
12 Kang, D. Y., Lee, J. Y., Kim, M. S., Kim, C. H., Kim, H. K., Lee, S. M., Kwon, Y. M., Lee, J. W., Baik, H. S., Yu, B. P. and Chung, H. Y. 2008. 4-Hydroxynonenal induces endothelial apoptosis through mitochondrial depolarization. J. Life Sci. 18, 1513-1520.   DOI
13 Lee, H. N., Jang, H. Y., Kim, H. J., Shin, S. A., Choo, G. S., Park, B. K., Kim, B. S. and Jung, J. Y. 2015. Induction of apoptosis by piceatannol in YD-15 human oral cancer cells. Prev. Nutr. Food Sci. 44, 975-982.
14 Lee, K. H. and Yang, S. C. 2009. Relation between cyclooxygenase-2 and polo-like kinase-1 in non-small cell lung cancer. KATRD 67, 303-310.
15 Park, H., Jin, C. Y., Choi, T. H., Hong, S. H. and Cho, Y. H. Effect of proapoptotic Bcl-2 on naringenin-induced apoptosis in human leukemia U937 cells. J. Life Sci. 23, 1118-2215.   DOI
16 Park, M. A. and Kang, K. J. 2015. Effect of grape skin extract on apoptosis in MDA-MB-231 human breast cancer cells. J. East Asian Soc. Dietary Life 25, 87-98.   DOI
17 Park, S. Y., Lee, S. H., Park, O. J and Kim, Y. M. 2011. Apoptotic effects of curcumin and EGCG via Akt-p53 signaling pathway in HCT116 colon cancer cells. J. Life Sci. 21, 89-95.   DOI
18 Ryu, J. H., Lee, S. J., Kim, M. J., Shin, J. H., Kang, S. K., Cho, K. M. and Sung, N. J. 2011. Antioxidant and anticancer activities of artemisia annua L. and determination of functional compounds. Prev. Nutr. Food Sci. 40, 509-516.
19 Tohru, Y. and Andrew, T. 2013. Autophagy and cell death. Essays Biochem. 55, 105-117.   DOI
20 Soung, Y. H., Lee, J. W., Kim, S. Y., Nam, S. W. and Park, W. S. 2005. Mutational analysis of proapoptotic bcl-2 Family genes in colon carcinomas. J. Pathol. Transl. Med. 39, 168-171.
21 Wu, G. S., Zou, S. Q., Liu, Z. R., Tang, Z. H. and Wang, J. H. 2003. Celecoxib inhibits proliferation and induces apoptosis via prostaglandin E2 pathway in human cholangiocarcinoma cell lines. World J. Gastroenterol. 9, 1302-1306.   DOI
22 Yewseok, S., Farrukh, A., Jeremy, J. J. and Hasan, M. 2009. A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kB-signaling pathways. Oxford Univ Press. 30, 300-307.
23 Yoko, O., Shohei, K., Toshiyuki, O., Yuko, I., Toshiaki, S., Keiji, T., Norihisa, M. and Yukiko, G. 2002. Akt enhances Mdm2-mediated ubiquitination and degradation of p53. J. Biol. Chem. 277, 21843-21850.   DOI
24 Yoon, M. Y., Kim, J. Y., Hwang, J. H., Cha, M. R., Lee, M. R., Jo, K. J. and Park, H. R. 2007. Protective effect of methanolic extracts from dendrobium nobile lindl. on H2O2-induced neurotoxicity in PC12 cells. J. Kor. Soc. Appl. Biol. Chem. 50, 63-67.