Abstract
Tormentic acid (TA), which is the main pentacyclic triterpene secondary metabolite formed by Eriobotrya japonica (Thunb.) Lindl., was purified by preparative HPLC and characterized by UPLC-MS. The inhibitory activity of the purified material towards hepatocellular carcinoma cells (HepG2, Bel-7405, Sk-hep-1) was evaluated based on proliferation, tumorigenesis, transformation, invasion and migration, as well as its ability to induce apoptosis in these cells. At concentrations of 22.5 μg/mL or more, TA led to considerable decreases in cell viability, colony formation and cell migration. TA treatment also induced apoptosis in the three hepatocellular carcinoma cell lines evaluated in this study. These effects were related to changes in the expression levels of Caspase3 and poly ADP-ribose polymerase, therefore highlighting the potent anti-cancer activity of TA towards all three of these cell lines.
Abbreviations
- CA:
-
Corosolic acid
- MA:
-
Maslinic acid
- OA:
-
Oleanolic acid
- TA:
-
Tormentic acid
- UA:
-
Ursolic acid
- HCC:
-
Hepatocellular carcinoma
- DW:
-
Dry weight
References
An HJ, Kim IT, Park HJ, Kim HM, Choi JH, Lee KT (2011) Tormentic acid, a triterpenoid saponin, isolated from Rosa rugosa, inhibited lps-induced inos, cox-2, and tnf-α expression through inactivation of the nuclear factor-κb pathway in raw 264.7 macrophages. Int Immunopharmacol 11:504–510. doi:10.1016/j.intimp.2011.01.002
Banno N, Akihisa T, Tokuda H, Yasukawa K, Higashihara H, Ukiya M, Watanabe K, Kimura Y, Hasegawa JI, Nishino H (2004) Triterpene acids from the leaves of perilla frutescens and their anti-inflammatory and antitumor-promoting effects. Biosci Biotechnol Biochem 68:85–90. doi:10.1271/bbb.68.85
Bortalanza LB, Ferreira J, Hess SC, Monache FD, YunesnRA, Calixto JB (2002) Anti-allodynic action of the tormentic acid, a triterpene isolated from plant, against neuropathic and inflammatory persistent pain in mice. Eur J Pharmacol 453:203–208
Chang CT, Huang SS, Lin SS, Amagaya S, Ho HY, Hou WC, Shie PH, Wu JB, Huang GJ (2011) Anti-inflammatory activities of tormentic acid from suspension cells of Eriobotrya japonica ex vivo, and in vivo. Food Chem 127:1131–1137. doi:10.1016/j.foodchem.2011.01.114
Cicalese L (2015) Hepatocellular carcinoma. Medscape drugs and diseases. http://emedicine.medscape.com/article/197319-overview. Accessed 28 Sept 2015
Fogo AS, Antonioli E, Calixto JB, Campos AH (2009) Tormentic acid reduces vascular smooth muscle cell proliferation and survival. Eur J Pharmacol 615:50–54. doi:10.1016/j.ejphar.2009.05.009
Georgiev MI, Weber J, Maciuk A (2009) Bioprocessing of plant cell cultures for mass production of targeted compounds. Appl Microbiol Biotechnol 83:809–823 doi:10.1007/s00253-009-2049-x
Hengartner MO (2000) The biochemistry of apoptosis. Nature. 407:770–776. doi:10.1038/35037710
Ho HY, Liang KY, Lin WC, Kitanaka S, Wu JB (2010) Regulation and improvement of triterpene formation in plant cultured cells of Eriobotrya japonica, Lindl. J Biosci Bioeng 110:588–592. doi:10.1016/j.jbiosc.2010.06.009
Jang SM, Yee ST, Choi J, Choi MS, Do GM, Jeon SM, Yeo J, Kim MJ, Seo KI, Lee MK (2009) Ursolic acid enhances the cellular immune system and pancreatic beta-cell function in streptozotocin-induced diabetic mice fed a high-fat diet. Int Immunopharmacol 9:113–119. doi:10.1016/j.intimp.2008.10.013
Kikuchi T, Akazawa H, Tabata K, Manosroi A, Manosroi J, Suzuki T, Akihisa T (2011) 3-o-(e)-p-coumaroyl tormentic acid from Eriobotrya japonica leaves induces caspase-dependent apoptotic cell death in human leukemia cell line. Chem Pharm Bull 59(3):378–381. doi:10.1248/cpb.59.378
Liang ZZ, Aquino R, De Feo V, De Simone F, Pizza C (1990) Polyhydroxylated triterpenes from Eriobotrya japonica. Planta Med 56:330–332. doi:10.1055/s-2006-960973
Loizzo MR, Bonesi M, Passalacqua NG, Saab A, Menichini F, Tundis R (2013) Antiproliferative activities on renal, prostate and melanoma cancer cell lines of sarcopoterium spinosum aerial parts and its major constituent tormentic acid. Anti-cancer Agents Med Chem 13:768–776. doi:10.2174/1871520611313050011
Machado DG, Neis VB, Balen GO, Colla A, Cunha MP, Dalmarco JB, Pizzolatti MG, Prediger RD, Rodrigues ALS (2012) Antidepressant-like effect of ursolic acid isolated from Rosmarinus officinalis L. in mice: evidence for the involvement of the dopaminergic system. Pharmacol Biochem Behav 103:204–211. doi:10.1016/j.pbb.2012.08.016
Rocha GDG, Simões M, Oliveira RR, Kaplan MAC, Gattass CR 2012 3β-acetyl tormentic acid induces apoptosis of resistant leukemia cells independently of P-gp/ABCB1 activity or expression. Invest New Drug 30:105–113. doi:10.1007/s10637-010-9524-1
Rosen J, Gottfries J, Muresan S, Backlund A, Oprea TI (2009) Novel chemical space exploration via natural products. J Med Chem 52:1953–1962. doi:10.1021/jm801514w
Shih CC, Ciou JL, Lin CH, Wu JB, Ho HY (2013) Cell suspension culture of Eriobotrya japonica regulates the diabetic and hyperlipidemic signs of high-fat-fed mice. Molecules 18:2726–2753. doi:10.3390/molecules18032726
Yu YX, Gu ZL, Yin JL, Chou WH, Kwok CY, Qin ZH, Liang ZQ (2010) Ursolic acid induces human hepatoma cell line SMMC-7721 apoptosis via p53-dependent pathway. Chin Med J 123:1915–1923. doi:10.3760/cma.j.issn.0366-6999.2010.14.016
Acknowledgements
Funding was provided by the National Natural Science Foundation of China (Grant No. 31501735) in 2016.
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by Silvia Moreno.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Li, HH., Su, MH., Yao, DH. et al. Anti-hepatocellular carcinoma activity of tormentic acid derived from suspension cells of Eriobotrya japonica (Thunb.) Lindl.. Plant Cell Tiss Organ Cult 130, 427–433 (2017). https://doi.org/10.1007/s11240-017-1221-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11240-017-1221-8