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Mirabijalone E: a novel rotenoid from Mirabilis himalaica inhibited A549 cell growth in vitro and in vivo.
J Ethnopharmacol 2014; 155(1):326-33JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

The roots of Mirabilis himalaica have been used in Tibetan folk medicine for treatment of uterine cancer, nephritis edematous, renal calculus and arthrodynia. In our previous work, the ethanol extract of roots had shown potent cytotoxicity against human cancer cells. However, no information is available on the antitumor effect of Mirabilis himalaica. The aim of the present study was to investigate the active constituents guided by bioassay and evaluate the related antitumor efficacy in vitro and in vivo.

MATERIALS AND METHODS

The active subextract (ethyl acetate) was subjected to successive chemical separation using a combination of silica gel, LH-20 chromatography and semi-preparative HPLC. The structures were determined by spectroscopic analysis techniques such as nuclear magnetic resonance (NMR) and mass spectrometry. Three human cancer cell lines, A549, HepG2 and HeLa were used for in vitro cytotoxicity evaluation of all isolated compounds by MTT-assay. Then, the potent and novel compound mirabijalone E was employed to the mechanism study againstA549 cells. BrdU immunofluorescence, soft agar assay and cell cycle analysis were employed to detect the cell proliferation effects. Annexin V-FITC/PI staining assay was used for examining apoptotic effects. Expression levels of apoptosis-related proteins were determined by western blot assay. in vivo tumorigenic assay was used to evaluate the xenograft tumor growth treated with mirabijalone E.

RESULTS

One new rotenoid compound, mirabijalone E, together with eight known rotenoids was isolated from Mirabilis himalaica. Mirabijalone E, 9-O-methyl-inone B, boeravinone C and boeravinone H exhibited cytotoxicity against A 549 and HeLa cells. Further study on mirabijalone E was carried out in vitro and in vivo. Mirabijalone E inhibited A549 cells growth in a time and dose-dependent manner, which arrested cell cycle in S phase. Mechanistically, mirabijalone E treatment resulted in the increase of Bax expression level, the decrease of Bcl-2 level and the activation of caspase-3, which suggested the activation of apoptosis cascades. Consequently, the xenograft treated with mirabijalone E showed markedly suppressed tumor growth.

CONCLUSIONS

The result suggested that mirabijalone E, together with active compounds, 9-O-methyl-4-hydroxyboeravinone B, boeravinone C and boeravinone H could be a promising candidate for cancer therapy.

Authors+Show Affiliations

Key Laboratory on Luminescence and Real-Time Analysis (Ministry of Education), College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China.Key Laboratory on Luminescence and Real-Time Analysis (Ministry of Education), College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China.Key Laboratory on Luminescence and Real-Time Analysis (Ministry of Education), College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China.Key Laboratory on Luminescence and Real-Time Analysis (Ministry of Education), College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China.Key Laboratory on Luminescence and Real-Time Analysis (Ministry of Education), College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China.Agriculture and Animal Husbandry College, Tibet University, Nyingchi, Tibet 860000, PR China.School of Life Sciences, Southwest University, Chongqing 400715, PR China.Key Laboratory on Luminescence and Real-Time Analysis (Ministry of Education), College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China. Electronic address: mminchen@swu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24882730

Citation

Linghu, Lang, et al. "Mirabijalone E: a Novel Rotenoid From Mirabilis Himalaica Inhibited A549 Cell Growth in Vitro and in Vivo." Journal of Ethnopharmacology, vol. 155, no. 1, 2014, pp. 326-33.
Linghu L, Fan H, Hu Y, et al. Mirabijalone E: a novel rotenoid from Mirabilis himalaica inhibited A549 cell growth in vitro and in vivo. J Ethnopharmacol. 2014;155(1):326-33.
Linghu, L., Fan, H., Hu, Y., Zou, Y., Yang, P., Lan, X., ... Chen, M. (2014). Mirabijalone E: a novel rotenoid from Mirabilis himalaica inhibited A549 cell growth in vitro and in vivo. Journal of Ethnopharmacology, 155(1), pp. 326-33. doi:10.1016/j.jep.2014.05.034.
Linghu L, et al. Mirabijalone E: a Novel Rotenoid From Mirabilis Himalaica Inhibited A549 Cell Growth in Vitro and in Vivo. J Ethnopharmacol. 2014 Aug 8;155(1):326-33. PubMed PMID: 24882730.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mirabijalone E: a novel rotenoid from Mirabilis himalaica inhibited A549 cell growth in vitro and in vivo. AU - Linghu,Lang, AU - Fan,Haixia, AU - Hu,Yijie, AU - Zou,Yanling, AU - Yang,Panpan, AU - Lan,Xiaozhong, AU - Liao,Zhihua, AU - Chen,Min, Y1 - 2014/05/29/ PY - 2014/03/24/received PY - 2014/05/20/revised PY - 2014/05/21/accepted PY - 2014/6/3/entrez PY - 2014/6/3/pubmed PY - 2015/4/8/medline KW - 9-O-methyl-4-hydroxyboeravinone B (PubChem CID: 487168) KW - Apoptosis KW - Boeravinone A (PubChem CID: 14018346) KW - Boeravinone B (PubChem CID: 14018348) KW - Boeravinone C (PubChem CID: 13940642) KW - Boeravinone D (PubChem CID: 15081178) KW - Boeravinone E (PubChem CID: 11537197) KW - Boeravinone F (PubChem CID: 12004175) KW - Boeravinone H (PubChem CID: 16745324) KW - Cell cycle KW - Cytotoxicity KW - Mirabijalone E KW - Mirabilis himalaica SP - 326 EP - 33 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 155 IS - 1 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Mirabilis himalaica have been used in Tibetan folk medicine for treatment of uterine cancer, nephritis edematous, renal calculus and arthrodynia. In our previous work, the ethanol extract of roots had shown potent cytotoxicity against human cancer cells. However, no information is available on the antitumor effect of Mirabilis himalaica. The aim of the present study was to investigate the active constituents guided by bioassay and evaluate the related antitumor efficacy in vitro and in vivo. MATERIALS AND METHODS: The active subextract (ethyl acetate) was subjected to successive chemical separation using a combination of silica gel, LH-20 chromatography and semi-preparative HPLC. The structures were determined by spectroscopic analysis techniques such as nuclear magnetic resonance (NMR) and mass spectrometry. Three human cancer cell lines, A549, HepG2 and HeLa were used for in vitro cytotoxicity evaluation of all isolated compounds by MTT-assay. Then, the potent and novel compound mirabijalone E was employed to the mechanism study againstA549 cells. BrdU immunofluorescence, soft agar assay and cell cycle analysis were employed to detect the cell proliferation effects. Annexin V-FITC/PI staining assay was used for examining apoptotic effects. Expression levels of apoptosis-related proteins were determined by western blot assay. in vivo tumorigenic assay was used to evaluate the xenograft tumor growth treated with mirabijalone E. RESULTS: One new rotenoid compound, mirabijalone E, together with eight known rotenoids was isolated from Mirabilis himalaica. Mirabijalone E, 9-O-methyl-inone B, boeravinone C and boeravinone H exhibited cytotoxicity against A 549 and HeLa cells. Further study on mirabijalone E was carried out in vitro and in vivo. Mirabijalone E inhibited A549 cells growth in a time and dose-dependent manner, which arrested cell cycle in S phase. Mechanistically, mirabijalone E treatment resulted in the increase of Bax expression level, the decrease of Bcl-2 level and the activation of caspase-3, which suggested the activation of apoptosis cascades. Consequently, the xenograft treated with mirabijalone E showed markedly suppressed tumor growth. CONCLUSIONS: The result suggested that mirabijalone E, together with active compounds, 9-O-methyl-4-hydroxyboeravinone B, boeravinone C and boeravinone H could be a promising candidate for cancer therapy. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/24882730/Mirabijalone_E:_a_novel_rotenoid_from_Mirabilis_himalaica_inhibited_A549_cell_growth_in_vitro_and_in_vivo_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(14)00403-6 DB - PRIME DP - Unbound Medicine ER -