Anti-Cancer Agents in Medicinal Chemistry

Author(s): Hui Fang and Hongmei Ji*

DOI: 10.2174/1871520619666191010102526

Furanocoumarin A: A Novel Anticancer Agent on Human Lung Cancer A549 Cells from Fructus liquidambaris

Page: [2091 - 2096] Pages: 6

  • * (Excluding Mailing and Handling)

Abstract

Background and Objective: The fruit of Fructus liquidambaris, which is recently being used for cancer treatment, has a history to be used as a traditional medicine in China for thousands of years.

Materials and Methods: Ten kg of dried F. liquidambaris was obtained with 70% alcohol-water solution under reflux for three times. The condensed extract was obtained from petroleum ether, ethyl acetate and N-butyl alcohol, respectively. Ethyl acetate extract was subjected to silica gel column, Sephadex LH-20, ODS column chromatography and RP-HPLC column chromatography to yield a new compound (1). The structure was identified through intensive analysis of NMR and MS spectra. The antitumor mechanism of the furanocoumarin A on human lung cancer A549 cells was confirmed by detecting the apoptosis-related proteins.

Results: Furanocoumarin A (1), a novel furanocoumarin constituent was isolated and identified from F. Liquidambaris. The IC50 value of furanocoumarin A on A549 cell lines was 65.28±5.36µM obtained by the method of MTT. The compound could induce the apoptosis of A549 cells by inducing 21.5% early apoptosis and 32.4% late apoptosis at the concentration of 60µmol/L. Western blot analysis indicated that protein expressions of p53, caspase 3 and Bax increased in a dose-dependent manner between the concentrations from 40 to 80µM. The protein expression of Bcl-2 decreased the concentration of 60 and 80µM. The ratio of Bcl-2 to Bax was inversely proportional to the dose concentration.

Conclusion: Furanocoumarin A could be a novel anticancer agent from herbal medicine.

Keywords: Fructus liquidambaris, furanocoumarin, A549, apoptosis, caspase 3, bax.

Graphical Abstract

[1]
Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA Cancer J. Clin., 2011, 61(2), 69-90.
[http://dx.doi.org/10.3322/caac.20107] [PMID: 21296855]
[2]
Raponi, M.; Zhang, Y.; Yu, J.; Chen, G.; Lee, G.; Taylor, J.M.; Macdonald, J.; Thomas, D.; Moskaluk, C.; Wang, Y.; Beer, D.G. Gene expression signatures for predicting prognosis of squamous cell and adenocarcinomas of the lung. Cancer Res., 2006, 66(15), 7466-7472.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-1191] [PMID: 16885343]
[3]
Symon, A.V.; Veselova, N.N.; Kaplun, A.P.; Vlasenkova, N.K.; Fedorova, G.A.; Liutik, A.I.; Gerasimova, G.K.; Shvrts, V.I. Synthesis and antitumor activity of cyclopropane derivatives of betulinic and betulonic acids. Bioorg. Khim., 2005, 31(3), 320-325.
[PMID: 16004391]
[4]
Yang, S.; Zhao, Q.; Xiang, H.; Liu, M.; Zhang, Q.; Xue, W.; Song, B.; Yang, S. Antiproliferative activity and apoptosis-inducing mechanism of constituents from Toona sinensis on human cancer cells. Cancer Cell Int., 2013, 13(1), 12.
[http://dx.doi.org/10.1186/1475-2867-13-12] [PMID: 23394678]
[5]
Zhang, X.J.; Li, H.W.; Ji, Y.B.; Fang, G.Z. Effects of betulonic acid on SGC-7901, HePG-2 and mice bearing S180 tumor cells. Nat. Prod. Res. Dev., 2009, 21, 766-770.
[6]
Zhang, X.J.; Han, L.; Ji, Y.B.; Fang, G.Z. Studies of betulonic acid on cell cycle and related protein expressions on mice of bearing H22 tumor cells. Chin. J. Chin. Mater. Med., 2008, 33(14), 1739-1743.
[PMID: 18841782]
[7]
Mendis, A.S.; Thabrew, I.; Ediriweera, M.K.; Samarakoon, S.R.; Tennekoon, K.H.; Adhikari, A.; de Silva, E.D. Isolation of a new sesquiterpene lactone from Vernonia zeylanica (L) Less and its anti-proliferative effects in breast cancer cell lines. Anticancer. Agents Med. Chem., 2019, 19(3), 410-424.
[http://dx.doi.org/10.2174/1871520619666181128163359] [PMID: 30488799]
[8]
Bergendorff, O.; Dekermendjian, K.; Nielsen, M.; Shan, R.; Witt, R.; Ai, J.; Sterner, O. Furanocoumarins with affinity to brain benzodiazepine receptors in vitro. Phytochemistry, 1997, 44(6), 1121-1124.
[http://dx.doi.org/10.1016/S0031-9422(96)00703-0] [PMID: 9055449]
[9]
Kaur, M.; Kohli, S.; Sandhu, S.; Bansal, Y.; Bansal, G. Coumarin: A promising scaffold for anticancer agents. Anticancer. Agents Med. Chem., 2015, 15(8), 1032-1048.
[http://dx.doi.org/10.2174/1871520615666150101125503] [PMID: 25553437]