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Ethyl acetate extract from Selaginella doederleinii Hieron inhibits the growth of human lung cancer cells A549 via caspase-dependent apoptosis pathway.
J Ethnopharmacol 2016; 190:261-71JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Selaginella doederleinii Hieron has been used as a folk medicine for the treatment of different cancers, especially for nasopharyngeal carcinoma, lung cancer and trophoblastic tumor in China. Previously, the ethyl acetate extract from S. doederleinii (SDEA extract) showed favorable anti-cancer potentials. However, the main chemical composition and anticancer mechanism of the SDEA extract were still not very clear. Until now, there are no reports available about the oral toxicity of the extract.

AIM OF STUDY

The present study was to further elucidate the chemical composition and anti-lung cancer mechanism of the SDEA extract, and evaluate the acute oral toxicity of the extract.

MATERIALS AND METHODS

The SDEA extract was separated and analysed by HPLC to disclose its main chemicals. The effects of the extract were then investigated in vitro on cell viability, apoptosis and cell cycle using fluorescence microscopy and flow cytometry, and the molecular mechanism against human lung cancer cells A549 was further studied by western blot assays. The in vivo anti-cancer effect of the extract was evaluated in A549 xenograft mice model by histochemical assay, and tumor growth, microvascular density (MVD) and Ki67 expression were also measured. In addition, acute oral toxicity test of the extract was executed in mice.

RESULTS

SDEA extract mainly contained eight biflavonoids. The extract caused the loss of mitochondrial membrane potential and induced cell apoptosis by upregulating Bax, downregulating Bcl-2, activating caspase-9 and caspase-3 and blocked the cell cycle in S phase. The extract reduced expression of antigen Ki67, decreased MVD, and significantly inhibited the tumor growth. The extract did not show apparent oral acute toxicity in healthy mice.

CONCLUSION

The SDEA extract exerted anti-tumor effect through activating mitochondrial pathways and reducing Ki67 expression and MVD. Low oral acute toxicity suggested it a promising chemotherapy agent.

Authors+Show Affiliations

Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou 350108, China; Provincial Clinical College of Fujian Medical University, Department of Pharmacy, Fuzhou 350001, China.Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou 350108, China.Department of TCM resource and Apitherapy, Bee Science College, Fujian Agriculture and Forestry University, Fuzhou 350002, China.Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou 350108, China.Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou 350108, China; Fujian Center For Disease Control & Prevention, Fuzhou 350001, China.Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou 350108, China.Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou 350108, China.Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou 350108, China. Electronic address: yauhung@126.com.Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou 350108, China. Electronic address: xhl1963@sina.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27292193

Citation

Sui, Yuxia, et al. "Ethyl Acetate Extract From Selaginella Doederleinii Hieron Inhibits the Growth of Human Lung Cancer Cells A549 Via Caspase-dependent Apoptosis Pathway." Journal of Ethnopharmacology, vol. 190, 2016, pp. 261-71.
Sui Y, Li S, Shi P, et al. Ethyl acetate extract from Selaginella doederleinii Hieron inhibits the growth of human lung cancer cells A549 via caspase-dependent apoptosis pathway. J Ethnopharmacol. 2016;190:261-71.
Sui, Y., Li, S., Shi, P., Wu, Y., Li, Y., Chen, W., ... Lin, X. (2016). Ethyl acetate extract from Selaginella doederleinii Hieron inhibits the growth of human lung cancer cells A549 via caspase-dependent apoptosis pathway. Journal of Ethnopharmacology, 190, pp. 261-71. doi:10.1016/j.jep.2016.06.029.
Sui Y, et al. Ethyl Acetate Extract From Selaginella Doederleinii Hieron Inhibits the Growth of Human Lung Cancer Cells A549 Via Caspase-dependent Apoptosis Pathway. J Ethnopharmacol. 2016 Aug 22;190:261-71. PubMed PMID: 27292193.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ethyl acetate extract from Selaginella doederleinii Hieron inhibits the growth of human lung cancer cells A549 via caspase-dependent apoptosis pathway. AU - Sui,Yuxia, AU - Li,Shaoguang, AU - Shi,Peiying, AU - Wu,Youjia, AU - Li,Yuxiang, AU - Chen,Weiying, AU - Huang,Liying, AU - Yao,Hong, AU - Lin,XinHua, Y1 - 2016/06/09/ PY - 2016/02/03/received PY - 2016/06/08/revised PY - 2016/06/08/accepted PY - 2016/6/14/entrez PY - 2016/6/14/pubmed PY - 2017/4/19/medline KW - A549 KW - Apoptosis KW - Lung cancer KW - Mitochondrial apoptotic pathways KW - Selaginella doederleinii Hieron SP - 261 EP - 71 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 190 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Selaginella doederleinii Hieron has been used as a folk medicine for the treatment of different cancers, especially for nasopharyngeal carcinoma, lung cancer and trophoblastic tumor in China. Previously, the ethyl acetate extract from S. doederleinii (SDEA extract) showed favorable anti-cancer potentials. However, the main chemical composition and anticancer mechanism of the SDEA extract were still not very clear. Until now, there are no reports available about the oral toxicity of the extract. AIM OF STUDY: The present study was to further elucidate the chemical composition and anti-lung cancer mechanism of the SDEA extract, and evaluate the acute oral toxicity of the extract. MATERIALS AND METHODS: The SDEA extract was separated and analysed by HPLC to disclose its main chemicals. The effects of the extract were then investigated in vitro on cell viability, apoptosis and cell cycle using fluorescence microscopy and flow cytometry, and the molecular mechanism against human lung cancer cells A549 was further studied by western blot assays. The in vivo anti-cancer effect of the extract was evaluated in A549 xenograft mice model by histochemical assay, and tumor growth, microvascular density (MVD) and Ki67 expression were also measured. In addition, acute oral toxicity test of the extract was executed in mice. RESULTS: SDEA extract mainly contained eight biflavonoids. The extract caused the loss of mitochondrial membrane potential and induced cell apoptosis by upregulating Bax, downregulating Bcl-2, activating caspase-9 and caspase-3 and blocked the cell cycle in S phase. The extract reduced expression of antigen Ki67, decreased MVD, and significantly inhibited the tumor growth. The extract did not show apparent oral acute toxicity in healthy mice. CONCLUSION: The SDEA extract exerted anti-tumor effect through activating mitochondrial pathways and reducing Ki67 expression and MVD. Low oral acute toxicity suggested it a promising chemotherapy agent. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/27292193/Ethyl_acetate_extract_from_Selaginella_doederleinii_Hieron_inhibits_the_growth_of_human_lung_cancer_cells_A549_via_caspase_dependent_apoptosis_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(16)30386-5 DB - PRIME DP - Unbound Medicine ER -