Abstract
Background
Hevea brasiliensis latex is generally cultivated for the use of rubber particles. Previous studies have shown that the antiproliferative activity of C-serum in hepatocellular carcinoma is not induced through the classical apoptotic signaling pathway. However, in a leukemic cell line, the anti-proliferation effect of latex C serum remained unclear.
Methods
Leukemic cell lines (K562 and U937) and human peripheral blood mononuclear cells (PBMCs) were examined for cell viability using the MTT assay. Flow cytometry was used for apoptotic cell detection by annexin V/PI staining. The expression levels of proapoptotic and antiapoptotic marker genes were measured by qRT‒PCR. Moreover, the caspase activities of the extrinsic and intrinsic apoptotic pathways were detected by enzymatic activities.
Results
Latex C-serum inhibited cell proliferation in the K562 and U937 leukemic cell lines but did not affect human PBMCs. Latex C-serum significantly induced the percentage of early and late apoptotic cells in the leukemic cell line. The expression levels of the pro-apoptotic marker genes BAD, BAX, and CASPASE3 significantly increased in the leukemic cell line after post-latex C-serum leukemic cell treatment. The extrinsic, intrinsic and common apoptotic pathways were also studied through caspase-8, -9, and -3 activities. Latex C-serum treatment significantly induced caspase-8, -9, and -3 activation in the K562 cell line and U937 cell line compared to the untreated cells.
Conclusions
These results indicate that latex C-serum enhanced anti-proliferation in leukemic cell lines by inducing apoptosis and caspase activation.
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Data availability
No data associated in the manuscript.
References
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20):2391–2405. https://doi.org/10.1182/blood-2016-03-643544
Whiteley AE, Price TT, Cantelli G, Sipkins DA (2021) Leukaemia: a model metastatic disease. Nat Rev Cancer 21(7):461–475. https://doi.org/10.1038/s41568-021-00355-z
Chaudhury SS, Morison JK, Gibson BE, Keeshan K (2015) Insights into cell ontogeny, age, and acute myeloid leukemia. Exp Hematol 43(9):745–755. https://doi.org/10.1016/j.exphem.2015.05.008
Nowell PC (2007) Discovery of the Philadelphia chromosome: a personal perspective. J Clin Invest 117(8):2033–2035. https://doi.org/10.1172/JCI31771
Dombret H, Gardin C (2016) An update of current treatments for adult acute myeloid leukemia. Blood 127(1):53–61. https://doi.org/10.1182/blood-2015-08-604520
Ferrara F, Schiffer CA (2013) Acute myeloid leukaemia in adults. Lancet 381(9865):484–495. https://doi.org/10.1016/S0140-6736(12)61727-9
Osman AEG, Deininger MW (2021) Chronic myeloid leukemia: modern therapies, current challenges and future directions. Blood Rev 49:100825. https://doi.org/10.1016/j.blre.2021.100825
Chandra-Kuntal K, Lee J, Singh SV (2013) Critical role for reactive oxygen species in apoptosis induction and cell migration inhibition by diallyl trisulfide, a cancer chemopreventive component of garlic. Breast Cancer Res Treat 138(1):69–79. https://doi.org/10.1007/s10549-013-2440-2
Hung PH, Hsieh MC, Lee SC, Huang XF, Chang KF, Chen SY, Lee MS, Tsai NM (2020) Effects of Cedrus atlantica extract on acute myeloid leukemia cell cycle distribution and apoptosis. Mol Biol Rep 47(11):8935–8947. https://doi.org/10.1007/s11033-020-05947-w
Shanmugam MK, Lee JH, Chai EZ, Kanchi MM, Kar S, Arfuso F, Dharmarajan A, Kumar AP, Ramar PS, Looi CY, Mustafa MR, Tergaonkar V, Bishayee A, Ahn KS, Sethi G (2016) Cancer prevention and therapy through the modulation of transcription factors by bioactive natural compounds. Semin Cancer Biol 40–41:35–47. https://doi.org/10.1016/j.semcancer.2016.03.005
Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35(4):495–516. https://doi.org/10.1080/01926230701320337
Yeang HY, Arif SA, Yusof F, Sunderasan E (2002) Allergenic proteins of natural rubber latex. Methods 27(1):32–45. https://doi.org/10.1016/S1046-2023(02)00049-X
Salome Abarca LF, Klinkhamer PGL, Choi YH (2019) Plant latex, from ecological interests to bioactive chemical resources. Planta Med 85(11–12):856–868. https://doi.org/10.1055/a-0923-8215
Daruliza KM, Lam KL, Yang KL, Priscilla JT, Sunderasan E, Ong MT (2011) Anti-fungal effect of Hevea brasiliensis latex C-serum on Aspergillus niger. Eur Rev Med Pharmacol Sci 15(9):1027–1033
Daruliza KM, Yang KL, Lam KL, Priscilla JT, Sunderasan E, Ong MT (2011) Anti-Candida albicans activity and brine shrimp lethality test of Hevea brasiliensis latex B-serum. Eur Rev Med Pharmacol Sci 15(10):1163–1171
Ong MTYK, Lam KL, Ong GA, Sunderasan E (2009) Susceptibility of HeLa (cancer-origin) cells to a sub-fraction of latex B serum. J Rubb Res 12:117–124
Lee YK, Lay LK, Mahsufi MS, Guan TS, Elumalai S, Thong OM (2012) Anti-proliferation effect of Hevea brasiliensis latex B-serum on human breast epithelial cells. Pak J Pharm Sci 25(3):645–650
Lam KL, Yang KL, Sunderasan E, Ong MT (2012) Latex C-serum from Hevea brasiliensis induces non-apoptotic cell death in hepatocellular carcinoma cell line (HepG2). Cell Prolif 45(6):577–585. https://doi.org/10.1111/j.1365-2184.2012.00841.x
Hwang JY, Wang YT, Shyu YS, Wu JS (2008) Antimutagenic and antiproliferative effects of roasted and defatted peanut dregs on human leukemic U937 and HL-60 cells. Phytother Res 22(3):286–290. https://doi.org/10.1002/ptr.2306
Ma HY, Wang CQ, He H, Yu ZY, Tong Y, Liu G, Yang YQ, Li L, Pang L, Qi HY (2020) Ethyl acetate extract of Caesalpinia sappan L. inhibited acute myeloid leukemia via ROS-mediated apoptosis and differentiation. Phytomedicine 68:153142. https://doi.org/10.1016/j.phymed.2019.153142
Hseu YC, Shen YC, Kao MC, Mathew DC, Karuppaiya P, Li ML, Yang HL (2019) Ganoderma tsugae induced ROS-independent apoptosis and cytoprotective autophagy in human chronic myeloid leukemia cells. Food Chem Toxicol 124:30–44. https://doi.org/10.1016/j.fct.2018.11.043
Rokah OH, Granot G, Ovcharenko A, Modai S, Pasmanik-Chor M, Toren A, Shomron N, Shpilberg O (2012) Downregulation of miR-31, miR-155, and miR-564 in chronic myeloid leukemia cells. PLoS ONE 7(4):e35501. https://doi.org/10.1371/journal.pone.0035501
Kuno S, Srinoun K, Penglong T (2020) The effects of Phorbol 12-myristate 13-acetate concentration on the expression of miR-155 and miR-125b and their macrophage function-related genes in the U937 cell line. J Toxicol Sci 45(12):751–761. https://doi.org/10.2131/jts.45.751
Lam KLY, Chow YL, Ong MT, Sunderasan E (2012) Susceptibility of human B lymphocyte cell lines to dialysed latex b- and c-sera fractions. J Rubber Res 15(3):187–195
Suffness MPJ (1990) Assays related to cancer drug discovery. In: Hostettmenn K (ed) Methods in plant biochemistry: assays for bioactivity, vol 6. Academic Press, London, pp 71–133
Saab AM, Lampronti I, Borgatti M, Finotti A, Harb F, Safi S, Gambari R (2012) In vitro evaluation of the anti-proliferative activities of the wood essential oils of three Cedrus species against K562 human chronic myelogenous leukaemia cells. Nat Prod Res 26(23):2227–2231. https://doi.org/10.1080/14786419.2011.643885
De Kouchkovsky I, Abdul-Hay M (2016) Acute myeloid leukemia: a comprehensive review and 2016 update. Blood Cancer J 6(7):e441. https://doi.org/10.1038/bcj.2016.50
Acknowledgements
This work was supported by the National Science, Research and Innovation Fund (NSRF) and Prince of Songkla University (Grant No. MET6505111S) and the Faculty of Medical Technology, Prince of Songkla University.
Funding
The National Science, Research and Innovation Fund (NSRF) and Prince of Songkla University (Grant No. MET6505111S).
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KS was the principal investigator and had primary responsibility for the conception and design of the project, helping perform the experiments, data analysis, and drafting and editing of the manuscript. HB contributed to the study design, interpretation of the data and editing of the manuscript. SH performed the experiments and analyzed the data. CS performed the preparation of latex C-serum and editing of the manuscript. NT, ST, and WW contributed to the data analysis and editing of the manuscript. All authors reviewed and approved the final version to be submitted for publication.
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This study was approved by the Ethics Committee, Faculty of Medical Technology, Prince of Songkla University [approval ID EC65-01].
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Buncherd, H., Hongmanee, S., Saechan, C. et al. Latex C-serum from Hevea brasiliensis induces apoptotic cell death in a leukemic cell line. Mol Biol Rep 50, 7515–7525 (2023). https://doi.org/10.1007/s11033-023-08687-9
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DOI: https://doi.org/10.1007/s11033-023-08687-9