Abstract
Glyasperin A is a flavonoid that was isolated from the leaves of Macaranga indica Wight, Euphorbiaceae, a Vietnamese traditional herbal medicine. This compound has been proven to have potential anticancer properties. However, its impact on cancer stem cells has not been identified. In this work, the potential of glyasperin A is described in terms of the cytotoxicity, cell cycle arrest, and apoptosis-inducible activities against the NTERA-2 pluripotent human embryonal carcinoma cell line. The results presented that glyasperin A strongly inhibited NTERA-2 cellular proliferation with a value for the growth inhibition concentration at 50% of 2 ± 0.009 µM and in a dose-dependent manner. Due to approximately 3 times reduction of its IC50 value, this compound seems to be more sensitive to NTERA-2 cancer stem cells than to the HEK-293A normal kidney embryonic cells (IC50 6.40 ± 0.09 µM). In addition, the NTERA-2 cell cycle was clearly arrested at the S-phase (56.73%) compared to the untreated control (38.22%). Besides, flow cytometry analysis revealed that glyasperin A induced apoptosis in association with increasing compound concentrations. In addition, significant activation of the caspase-3 apoptotic enzyme under glyasperin A treatment was also recorded (p < 0.001). Therefore, glyasperin A demonstrated a potential effectiveness for the treatment of cancer stem cells.
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The data used to support the findings of this study are available from the corresponding authors upon request.
References
Arung ET, Sinamabela JR, Rosamah E, Kusuma IW, Kuspradini H, Alam AE, Amen Y, Tanaka H, Satria D, Shimizu K (2019) Antioxidant and antimelanogenesis activities of glyasperin A from Macaranga pruinosa leaves. Nat Prod Comm 14:1934578X19867192. https://doi.org/10.1177/1934578X19867192
Capp J-P (2019) Cancer stem cells: from historical roots to a new perspective. J Oncol 2019:5189232. https://doi.org/10.1155/2019/5189232
Desai A, Yan Y, Gerson SL (2019) Concise reviews: cancer stem cell targeted therapies: toward clinical success. Stem Cells Transl Med 8:75–81. https://doi.org/10.1002/sctm.18-0123
Do TT, Do TP, Nguyen TN, Nguyen TC, Vu TTP, Nguyen TGA (2019) Nanoliposomal L-asparaginase and its antitumor activities in Lewis lung carcinoma tumor-induced BALB/c mice. Adv Mater Sci Eng 2019:3534807. https://doi.org/10.1155/2019/3534807
Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516. https://doi.org/10.1080/01926230701320337
Gómez V, Hergovich A (2016) Cell-cycle control and DNA-damage signaling in mammals. In: I Kovalchuk, O Kovalchuk (eds) Genome stability. Academic Press, Elsevier, pp 227–242. https://doi.org/10.1016/B978-0-12-803309-8.00014-8
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674. https://doi.org/10.1016/j.cell.2011.02.013
Huong DTM, Anh LT, Cuc NT, Nhiem NX, Tai BH, Van Kiem P, Litaudon M, Thach TD, Van Minh C, Pham VC (2019) Cytotoxic prenylated flavonoids from the leaves of Macaranga indica. Phytochem Lett 34:39–42. https://doi.org/10.1016/j.phytol.2019.09.001
Matthews HK, Bertoli C, de Bruin RAM (2022) Cell cycle control in cancer. Nat Rev Mol Cell Bio 23:74–88. https://doi.org/10.1038/s41580-021-00404-3
McIlwain DR, Berger T, Mak TW (2013) Caspase functions in cell death and disease. CSH Perspect Bio 5:a008656. https://doi.org/10.1101/cshperspect.a008656
Meeran SM, Katiyar SK (2008) Cell cycle control as a basis for cancer chemoprevention through dietary agents. Front Biosci-Landmark 13:2191. https://doi.org/10.2741/2834
Nomura T, Zeng L, Fukai T, Zhang R-Y, Lou Z-C (1992) Four new prenylated flavonoids, glyasperins A, B, C, and D from the roots of Glycyrrhiza aspera. Heterocycles 34:575–587. https://doi.org/10.3987/COM-91-5951
Petsalaki E, Zachos G (2020) DNA damage response proteins regulating mitotic cell division: double agents preserving genome stability. FEBS J 287:1700–1721. https://doi.org/10.1111/febs.15240
Pierce GB, Speers WC (1988) Tumors as caricatures of the process of tissue renewal: prospects for therapy by directing differentiation. Cancer Res 48:1996–2004
Rewa RWS, Saputri RD, Tjahjandarie TS, Tanjung M (2020) Cytotoxic activity of flavonols from Macaranga gigantea (Rchb. f. and Zoll.) Müll. Arg. Pharmacy Pharm J Indonesia 17:360–367. https://doi.org/10.30595/pharmacy.v17i2.7649
Tang D, Kang R (2022) Cell death: machinery and regulation. In: Liao D (ed). Mechanisms of cell death and opportunities for therapeutic development. Elsevier, Academic Press, pp 47–64. https://doi.org/10.1016/B978-0-12-814208-0.00003-8
Visconti R, Della Monica R, Grieco D (2016) Cell cycle checkpoint in cancer: a therapeutically targetable double-edged sword. J Exp Clin Canc Res 35:153. https://doi.org/10.1186/s13046-016-0433-9
Walcher L, Kistenmacher A-K, Suo H, Kitte R, Dluczek S, Strauß A, Blaudszun A-R, Yevsa T, Fricke S, Kossatz-Boehlert U (2020) Cancer stem cells—origins and biomarkers: perspectives for targeted personalized therapies. Front Immunol 11:1280. https://doi.org/10.3389/fimmu.2020.01280
Yang D-S, Peng W-B, Yang Y-P, Liu K-C, Li X-L, Xiao W-L (2015) Cytotoxic prenylated flavonoids from Macaranga indica. Fitoterapia 103:187–191. https://doi.org/10.1016/j.fitote.2015.04.002
Acknowledgements
The authors thank Dr. Bui Huu Tai, Institute of Marine Biochemistry, Vietnam Academy of Science and Technology (VAST), for his support to run TLC and NMR analyses.
Funding
The research is funded by the Vietnam Academy of Science and Technology (VAST) under Grant No. TĐTBG0.03/21–23.
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DTT, CHH: conceptualization. DTT: investigation and writing of original draft. TSM, DTP, NXN, NTN: experimental data acquisition. TSM, NTN, DTT: methodology, manuscript review and editing. THP, NTC: supervision and experimental validation. All authors have read and approved the final submission.
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Mai, T.S., Phuong, D.T., Nga, N.T. et al. Glyasperin A from Macaranga indica Presents Promising Capacities Against NTERA-2 Cancer Stem Cells. Rev. Bras. Farmacogn. 33, 191–197 (2023). https://doi.org/10.1007/s43450-022-00350-x
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DOI: https://doi.org/10.1007/s43450-022-00350-x