<em>In vitro</em> anticancer activity of acetylshikonin action against cervical cancer
DOI:
https://doi.org/10.14719/pst.2014.1.2.15Keywords:
Cervix cancer, Siha cell, acetylshikonin, natural productsAbstract
Cervical cancer is a malignant neoplasm and is the second commonest cancer in women worldwide. Despite the availability of various treatment modalities, the 5-year survival remains poor. Therefore, it is absolutely necessary to explore drugs capable of preventing and treating cervical cancer. Plant-derived natural products are widely used as adjunct to chemotherapy for this type of cancer. Our study aims to investigate the effects of acetylshikonin, an acetyl derivative, isolated from a Chinese medicinal herb Lithospermum erythrorhizon Sieb. et Zucc., a folk medicine with a long history of safe use for clinically treating cervical cancer in China. MTT assay was used to determine the in vitro anticancer effects of acetylshikonin on human cervical cancer Siha cells. The expression of caspase-3 and -8 proteins were determined. Flow cytometry and quantitative RT-PCR were performed to detect the expression level of Siha cells associated markers and regulatory genes. In Siha cell lines, acetylshikonin inhibited cell growth in a dose-dependent manner. The preferential expression of Siha cells related marker, regulatory genes were also highlighted. It arrested the cell cycle by blocking transition from S phase to G2/M phase and induced apoptosis of Siha cell through activating caspase-3 and caspase-8. In the current study, acetylshikonin can be taken as a promising natural lead for cervical cancer.Downloads
References
Alley, M. C., Scudiero, D. A., Monks, A., Hursey, M. L., Czerwinski, M. J., Fine, D. L., ... Boyd, M. R. (1988). Feasibility of drug screenig with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Research, 48, 589-01. PMid:3335022
Chung, H. S., Kang, M., Cho, C., Park, S., Kim, H., Yoon, Y. S., ... Bae, H. (2005). Inhibition of lipopolysaccharide and interferon-gamma-induced expression of inducible nitric oxide synthase and tumor necrosis factor-alpha by Lithospermi radix in mouse peritoneal macrophages. Journal of Ethnopharmacology, 102, 412-7. PMid:16054790. doi:10.1016/j.jep.2005.06.028.
Chung, S. H., & Lambert, P. F. (2009). Prevention and treatment of cervical cancer in mice using estrogen receptor antagonists. Proceedings of the National Academy of Sciences of the United States of America, 106(46), 19467-72. doi:10.1073/pnas.0911436106. PMid:19901334.
Dzoyem, J. P., Nkuete, A. H., Kuete, V., Tala, M. F., Wabo, H. K., Guru, S. K., ... Tan, N. H. (2012). Cytotoxicity and antimicrobial activity of the methanol extract and compounds from Polygonum limbatum. Planta Medica, 78(8), 787-92. doi:10.1055/s-0031-1298431. PMid:22495442
Fang, X. L., Shao, L., Zhang, H., & Wang, S. M. (2005). CHMIS-C: A Comprehensive Herbal Medicine Information System for Cancer. Journal of Medicinal Chemistry, 48, 1481–8 doi:10.1021/jm049838d. PMid:15743190
Henares, T. G., Mizutani, F., Sekizawa, R., & Hisamoto, H. (2008). Single-drop analysis of various proteases in a cancer cell lysate using a capillary-assembled microchip. Analytical and Bioanalytical Chemistry, 391(7), 2507-12. doi:10.1007/s00216-008-2105-x. PMid:18431562
Kelly, J. G., Angelov, P. P., Trevisan, J., Vlachopoulou, A., Paraskevaidis, E., Martin-Hirsch, P. L., & Martin, F. L. (2010). Robust classification of low-grade cervical cytology following analysis with ATR-FTIR spectroscopy and subsequent application of self-learning classifier eClass. Analytical and Bioanalytical Chemistry, 398(5), 2191-201. doi:10.1007/s00216-010-4179-5. PMid:20857283
Kim, D. H., Jarvis, R. M., Allwood, J. W., Batman, G., Moore, R. E., Marsden-Edwards, E., ... Goodacre, R. (2010). Raman chemical mapping reveals site of action of HIV protease inhibitors in HPV16 E6 expressing cervical carcinoma cells. Analytical and Bioanalytical Chemistr., 398(7-8), 3051-61. doi:10.1007/s00216-010-4283-6. PMid:20957472
Kim, E. K., Kim, E. Y., Moon, P. D., Um, J. Y., Kim, H. M., Lee, H. S., ... Sohn, N. W. (2007). Lithospermi radix extract inhibits histamine release and production of inflammatory cytokine in mast cells. Bioscience, Biotechnology, and Biochemistry, 71, 2886-92. PMid:18071264
Masuda, Y., Nishida, A., Hori, K., Hirabayashi, T., Kajimoto, S., Nakajo, S., ... Nakaya, K. (2003). Beta-hydroxyisovalerylshikonin induces apoptosis in human leukemia cells by inhibiting the activity of a polo-like kinase 1 (PLK1). Oncogene, 22, 1012-23. doi:10.1038/sj.onc.1206200
Mu, L. H., Wei, N. Y., & Liu, P. (2012). Cytotoxic triterpenoid saponins from Ardisia gigantifolia. Planta Medica, 78(6), 617-21. doi:10.1055/s-0031-1298254. PMid:22314414
O'Keefe, B. R., Vojdani, F., Buffa, V., Shattock, R. J., Montefiori, D. C., Bakke, J., ... Palmer, K. E. (2009). Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component. Proceedings of the National Academy of Sciences of the United States of America, 106(15), 6099-104. doi:10.1073/pnas.0901506106. PMCid:PMC2662964
Singh, F., Gao, D., & Lebwohl, M. G. (2003). Shikonin modulates cell proliferation by inhibiting epidermal growth factor receptor signaling in human epidermoid carcinoma cells. Cancer Letter, 200, 115-21. doi:10.1016/S0304-3835(03)00239-8
Staniforth, V., Wang, S. Y., Shyur, L. F., & Yang, N. S. (2004). Shikonins, phytocompounds from Lithospermum erythrorhizon, inhibit the transcriptional activation of human tumor necrosis factor alpha promoter in vivo. The Journal of Biological Chemistry, 279, 5877-85. doi:10.1074/jbc.M309185200. PMid:14645256
Takai, N., Ueda, T., Nishida, M., Nasu, K., & Narahara, H. (2008). Beta-hydroxyisovalerylshikonin has a profound anti-growth activity in human endometrial and ovarian cancer cells. Gynecologic Oncology, 109, 107-14. PMid:18234298. doi:10.1016/j.ygyno.2007.12.020.
Van der Greef, J., Martin, S., Juhasz, P., Adourian, A., Plasterer, T., Verheij, E. R., & McBurney, R. N. (2007). The art and practice of systems biology in medicine: mapping patterns of relationships. Journal of Proteome Research, 6, 1540-59 doi:10.1021/pr0606530. PMid:17373844
Xiong, W., Luo, G., Zhou, L., Zeng, Y., & Yang, W. (2009). In vitro and in vivo antitumor effects of acetylshikonin isolated from Arnebia euchroma (Royle) Johnst (Ruanzicao) cell suspension cultures. Chinese Medicine, 4, 14-6. PMid:19594888. doi:10.1186/1749-8546-4-14.
Yue, Q. X., Cao, Z. W., Guan, S. H., Liu, X. H., Tao, L., Wu, W. Y., ... Guo, D. A. (2008). Proteomics characterization of the cytotoxicity mechanism of ganoderic acid D and computer-automated estimation of the possible drug target network. Molecular & Cellular Proteomics, 7(5), 949-61. doi:10.1074/mcp.M700259-MCP200
Zhang, G. G., Jing, Y., Zhang, H. M., Ma, E. L., Guan, J., Xue, F. N., ... Sun, X. Y. (2012). Isolation and cytotoxic activity of selaginellin derivatives and biflavonoids from Selaginella tamariscina. Planta Medica, 78(4), 390-2. doi:10.1055/s-0031-1298175. PMid:22271084
Downloads
Published
How to Cite
Issue
Section
License
Copyright and Licence details of published articles
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
Open Access Policy
Plant Science Today is an open access journal. There is no registration required to read any article. All published articles are distributed under the terms of the Creative Commons Attribution License (CC Attribution 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited (https://creativecommons.org/licenses/by/4.0/). Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
