Bigelovii A induces apoptosis of HL‑60 human acute promyelocytic leukaemia cells

Guan,Fuqin; Wang,Haiting; Shan,Yu; Zhang,Dongmei; Zhao,Youyi; Chen,Yu; Wang,Qizhi; Wang,Ming; Feng,Xu

doi:10.3892/mmr.2013.1353

Bigelovii A induces apoptosis of HL‑60 human acute promyelocytic leukaemia cells

Authors:
- Fuqin Guan
- Haiting Wang
- Yu Shan
- Dongmei Zhang
- Youyi Zhao
- Yu Chen
- Qizhi Wang
- Ming Wang
- Xu Feng
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Affiliations: Jiangsu Center for Research and Development of Medicinal Plants, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, Jiangsu, P.R. China, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, P.R. China, Dongtai Institute of Tidal Flat, Nanjing Branch of the Chinese Academy of Sciences, Dongtai, Jiangsu, P.R. China
Published online on: March 1, 2013 https://doi.org/10.3892/mmr.2013.1353
Pages: 1585-1590

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Abstract

In the present study, the antitumor effects of the nor‑Oleanane type triterpene saponin, Bigelovii A, isolated from Salicornia bigelovii Torr, were examined. Bigelovii A was demonstrated to inhibit HL‑60 human acute promyelocytic leukaemia cell growth with an IC50 value of 2.15 µg/ml. In addition, Bigelovii A promoted apoptosis in HL‑60 cells, as shown by apoptotic morphological changes and the hypodiploid cell assay. Apoptotic induction by Bigelovii A was associated with the downregulation of Bcl‑2, the upregulation of Bax and the activation of caspase‑3, as demonstrated by RT‑PCR and western blot analysis. In addition, a lactate dehydrogenase release test indicated that Bigelovii A may exhibit cytotoxic activity by the induction of cell membrane impairment. This study is the first to identify that Bigelovii A exhibits potential antitumor activity and induces marked apoptosis and membrane permeabilisation in HL‑60 cells. Bigelovii A may be a novel candidate for future cancer therapy.

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1	Ghobrial IM, Witzig TE and Adjei AA: Targeting apoptosis pathways in cancer therapy. CA Cancer J Clin. 55:178–194. 2005. View Article : Google Scholar : PubMed/NCBI
2	Wang SR and Fang WS: Pentacyclic triterpenoids and their saponins with apoptosis-inducing activity. Curr Top Med Chem. 9:1581–1596. 2009. View Article : Google Scholar : PubMed/NCBI
3	Zhang Z, Gao J, Cai XT, et al: Escin sodium induces apoptosis of human acute leukemia Jurkat T cells. Phytother Res. 25:1747–1755. 2011. View Article : Google Scholar : PubMed/NCBI
4	Shen DY, Kang JH, Song W, Zhang WQ, Li WG, Zhao Y and Chen QX: Apoptosis of human cholangiocarcinoma cell lines induced by β-escin through mitochondrial caspase-dependent pathway. Phytother Res. 25:1519–1526. 2011.
5	Thao NT, Hung TM, Cuong TD, et al: 28-nor-oleanane-type triterpene saponins from Camellia japonica and their inhibitory activity on LPS-induced NO production in macrophage RAW264.7 cells. Bioorg Med Chem Lett. 20:7435–7439. 2010.PubMed/NCBI
6	Thao NT, Hung TM, Lee MK, Kim JC, Min BS and Bae K: Triterpenoids from Camellia japonica and their cytotoxic activity. Chem Pharm Bull (Tokyo). 58:121–124. 2010.PubMed/NCBI
7	Min BS, Oh SR, Ahn KS, et al: Anti-complement activity of norlignans and terpenes from the stem bark of Styrax japonica. Planta Med. 70:1210–1215. 2004. View Article : Google Scholar : PubMed/NCBI
8	Xiao WL, Yang SY, Yang LM, et al: Chemical constituents from the leaves and stems of Schisandra rubriflora. J Nat Prod. 73:221–225. 2010. View Article : Google Scholar : PubMed/NCBI
9	Wei Y, Ma CM, Chen DY and Hattori M: Anti-HIV-1 protease triterpenoids from Stauntonia obovatifoliola Hayata subsp intermedia. Phytochemistry. 69:1875–1879. 2008. View Article : Google Scholar : PubMed/NCBI
10	Avilla J, Teixidò A, Velázquez C, Alvarenga N, Ferro E and Canela R: Insecticidal activity of Maytenus species (Celastraceae) nortriterpene quinone methides against codling moth, Cydia pomonella (L.) (Lepidoptera, tortricidae). J Agric Food Chem. 48:88–92. 2000.
11	Akihisa T, Takahashi A, Kikuchi T, et al: The melanogenesis-inhibitory, anti-inflammatory and chemopreventive effects of limonoids in n-hexane extract of Azadirachta indica A. Juss. (neem) seeds. J Oleo Sci. 60:53–59. 2011. View Article : Google Scholar : PubMed/NCBI
12	Yoshikawa M, Morikawa T, Fujiwara E, Ohgushi T, Asao Y and Matsuda H: New noroleanane-type triterpene saponins with gastroprotective effect and platelet aggregation activity from the flowers of Camellia japonica: Revised structures of camellenodiol and camelledionol. Heterocycles. 55:1653–1657. 2001. View Article : Google Scholar
13	Wang H, Tian XA and Ying GQ: A new nortriterpene from the root of Celastrus hypoleucus. Helv Chim Acta. 93:1628–1633. 2010. View Article : Google Scholar
14	Cheng YB, Liao TC, Lo YW, et al: Nortriterpene lactones from the fruits of Schisandra arisanensis. J Nat Prod. 73:1228–1233. 2010. View Article : Google Scholar : PubMed/NCBI
15	Kwon JH, Chang MJ, Seo HW, et al: Triterpenoids and a sterol from the stem-bark of Styrax japonica and their protein tyrosine phosphatase 1B inhibitory activities. Phytother Res. 22:1303–1306. 2008.PubMed/NCBI
16	Wang QZ, Liu XF, Shan Y, et al: Two new nortriterpenoid saponins from Salicornia bigelovii Torr. and their cytotoxic activity. Fitoterapia. 83:742–749. 2012. View Article : Google Scholar : PubMed/NCBI
17	Youle RJ and Strasser A: The BCL-2 protein family: opposing activities that med iate cell death. Nat Rev Mol Cell Biol. 9:47–59. 2008. View Article : Google Scholar : PubMed/NCBI
18	Burnett AK and Eden OB: The treatment of acute leukaemia. Lancet. 349:270–275. 1997. View Article : Google Scholar : PubMed/NCBI
19	Schmid C, Schleuning M, Schwerdtfeger R, et al: Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation. Blood. 108:1092–1099. 2006. View Article : Google Scholar
20	Kim H, Yoon SC, Lee TY and Jeong D: Discriminative cytotoxicity assessment based on various cellular damages. Toxicol Lett. 184:13–17. 2009. View Article : Google Scholar : PubMed/NCBI
21	Wang J, Zhao XZ, Qi Q, et al: Macranthoside B, a hederagenin saponin extracted from Lonicera macranthoides and its anti-tumor activities in vitro and in vivo. Food Chem Toxicol. 47:1716–1721. 2009. View Article : Google Scholar : PubMed/NCBI
22	Guan F, Shan Y, Zhao X, et al: Apoptosis and membrane permeabilisation induced by macranthoside B on HL-60 cells. Nat Prod Res. 25:332–340. 2011. View Article : Google Scholar : PubMed/NCBI
23	Tortora G, Caputo R, Damiano V, et al: Combined targeted inhibition of bcl-2, bcl-XL, epidermal growth factor receptor, and protein kinase A type I causes potent antitumor, apoptotic, and antiangiogenic activity. Clin Cancer Res. 9:866–871. 2003.
24	Tsujimoto Y: Cell death regulation by the Bcl-2 protein family in the mitochondria. J Cell Physiol. 195:158–167. 2003. View Article : Google Scholar : PubMed/NCBI
25	Wei MC, Zong WX, Cheng EH, et al: Proapoptotic BAX and BAK, a requisite gateway to mitochondrial dysfunction and death. Science. 292:727–730. 2001. View Article : Google Scholar : PubMed/NCBI
26	Kirkin V, Joos S and Zörning M: The role of Bcl-2 family members in tumorigenesis. Biochim Biophys Acta. 1644:229–249. 2004. View Article : Google Scholar : PubMed/NCBI
27	Manion MK and Hockenbery DM: Targeting BCL-2-related proteins in cancer therapy. Cancer Biol Ther. 2(4 Suppl 1): S105–S114. 2003. View Article : Google Scholar : PubMed/NCBI
28	Riedl SJ and Shi Y: Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol. 5:897–907. 2004. View Article : Google Scholar : PubMed/NCBI