Abstract
Objective
To investigate the potential effect of pure total flavonoids from Citrus paradisi Macfad peel (PTFC) on the proliferation of human myeloid leukemia cells Kasumi-1, HL-60 and K562, and the underlying mechanisms.
Methods
PTFC was extracted from Citrus paradisi Macfad peel and was identified by high performance liquid chromatography. The effect of PTFC on the proliferation and apoptosis of leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, fluorescent microscopy and flow cytometry, respectively. The effect of PTFC on the expression levels of apoptosis-related regulators was determined by Western blot assay.
Results
Treatment with PTFC inhibited leukemia cell proliferation in a dose- and time-dependent manner and triggered Kasumi-1 cell apoptosis. Treatment with PTFC significantly increased the levels of activated poly adenosine diphosphate-ribosepolymerase and caspase-3/-9, but reduced the levels of Mcl-1 expression in Kasumi-1 cells. However, PTFC did not obviously induce HL-60 cell apoptosis.
Conclusion
PTFC inhibited leukemia cell proliferation and induced their apoptosis by modulating apoptosisrelated regulator expression in leukemia cells in vitro.
Similar content being viewed by others
References
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009;114:937–951.
Goldman JM, Melo JV. Chronic myeloid leukemia-advances in biology and new approaches to treatment. N Engl J Med 2003;349:1451–1464.
Schlenk RF, Döhner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med 2008;358:1909–1918.
Parekh HS, Liu G, Wei MQ. A new dawn for the use of traditional Chinese medicine in cancer therapy. Mol Cancer 2009;8:21.
Havsteen BH. The biochemistry and medical significance of the flavonoids. Pharmacol Ther 2002;96:67–202.
Middleton E, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000;52:673–751.
Leung HW, Yang WH, Lai MY, Lin CJ, Lee HZ. Inhibition of 12-lipoxygenase during baicalein-induced human lung nonsmall carcinoma H460 cell apoptosis. Food Chem Toxicol 2007;45:403–411.
Ranelletti FO, Maggiano N, Serra FG, Ricci R, Larocca LM, Lanza P, et al. Quercetin inhibits p21-RAS expression in human colon cancer cell lines and in primary colorectal tumors. Int J Cancer 2000;85:438–445.
Salucci M, Stivala LA, Maiani G, Bugianesi R, Vannini V. Flavonoids uptake and their effect on cell cycle of human colon adenocarcinoma cells (Caco2). Br J Cancer 2002;86:1645–1651.
Girennavar B, Jayaprakasha GK, Jifon JL, Patil BS. Variation of bioactive furocoumarins and flavonoids in different varieties of grapefruits and pummelo. Eur Food Res Tech 2008;226:1269–1275.
Patil BS, Jayaprakasha GK, Chidambara Murthy KN, Vikram A. Bioactive compounds: historical perspectives, opportunities, and challenges. J Agric Food Chem 2009;57:8142–8160.
Uckoo RM, Jayaprakasha GK, Patil BS. Rapid separation method of polymethoxyflavones from citrus using flash chromatography. Separ Purificat Technol 2011;81:151–158.
Uckoo RM, Jayaprakasha GK, Balasubramaniam VM, Patil BS. Grapefruit (Citrus paradisi Macfad) phytochemicals composition is modulated by household processing techniques. J Food Sci 2012;77:C921–C926.
Crowder RN, El-Deiry WS. Caspase-8 regulation of trailmediated cell death. Exp Oncol 2012;34:160–164.
Ye XQ, ed. Citrus processing and utilization. Beijing: China Light Industry Publishing House; 2005:13–25.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by Zhejiang Provincial Natural Science Foundation of China (No. LY14H080003)
Rights and permissions
About this article
Cite this article
Dai, Ty., Wang, B., Lin, Sy. et al. Pure total flavonoids from Citrus paradisi Macfad induce leukemia cell apoptosis in vitro . Chin. J. Integr. Med. 23, 370–375 (2017). https://doi.org/10.1007/s11655-016-2593-z
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11655-016-2593-z