Antiproliferative and apoptotic effect of Knobweed (Hyptis capitata) root methanol extract on WiDr colorectal cancer cells
DOI:
https://doi.org/10.14719/pst.2379Keywords:
Anti-cancer, ethnobotany, GC-MS, doubling time, annexin V-PIAbstract
Methanol extract of Knobweed (Hyptis capitata) root has cytotoxic activity on WiDr cells, but the mechanism of its anticancer action as well as the secondary metabolite contents have not been further explored. This study aimed to extract the roots of H. capitata by a graded maceration, using absolute chloroform and absolute methanol. Methanol extract was used for subsequent assays to trace the mechanism of anti-cancer action. Tests carried out include a doubling time test with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide as well as an apoptosis test with Annexin V-PI Flow cytometry method. The secondary metabolite content was identified by the Gas Chromatography-Mass Spectrometry (GC-MS). The results showed that, H. capitata root methanol extract treatment caused morphological changes on WiDr cells. Moreover, the treatment suppressed the cellular proliferation, indicating that it can provide an anti-proliferation effect. Furthermore, the extract treatment at IC50 and 2IC50 caused 65.45% and 97.6% of apoptosis cells respectively. These results proved that H. capitata root methanolic extract has anticancer activity with anti-proliferation properties and the ability to trigger apoptosis on WiDr cells. Phytochemical compounds that might play a role as anti-cancer, among others include chatecol, 9-hexadecanoic acid, hexadecanoid acid-ethyl ester, methyl stearate, ferruginol, retinoic acid, campesterol, stigmasterol and ?-sitosterol.
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To’bungan N, Widyarini S, Nugroho LH, Pratiwi R. Ethnopharmacology of Hyptis capitata. Plant Sci Today. 1952;9(3):593-600. https://doi.org/10.14719/pst.1602
Yamagishi T, Zhang DC, Chang JJ, McPhail DR, McPhail AT, Lee KH. The cytotoxic principles of Hyptis capitata and the structures of the new triterpenes hyptatic acid-A and -B. Phytochemistry. 1988;27(10):3213-3216. https://doi.org/10.1016/0031-9422(88)80028-1
To’bungan N, Jati WN, Zahida F. Acute toxicity and anticancer potential of knobweed (Hyptis capitata) ethanolic leaf extract and fraction. Plant Sci Today. 2022;9(4):955-962. https://doi.org/10.14719/pst.1847
To’bungan N, Pratiwi R, Widyarini S, Nugroho LH. Cytotoxicity extract and fraction of knobweed (Hyptis capitata) and its effect on migration and apoptosis of T47D cells. Biodiversitas. 2022;23(1):572-580. https://doi.org/10.13057/biodiv/d230162
De Souza Rosa L, Jordão NA, Da Costa Pereira Soares N, De Mesquita JF, Monteiro M, Teodoro AJ. Pharmacokinetic, antiproliferative and apoptotic effects of phenolic acids in human colon adenocarcinoma cells using in vitro and in silico approaches. Molecules. 2018;23(10):2569. https://doi.org/10.3390/molecules23102569
Aung TN, Qu Z, Kortschak RD, Adelson DL. Understanding the Effectiveness of Natural Compound Mixtures in Cancer through Their Molecular Mode of Action. Int J Mol Sci. 2017;18(3):656. https://doi.org/10.3390/ijms18030656.
Anonymous. Technical data sheet, FITC anexin V apoptosis detection kit I, BDBioscience. [Internet]. 2008 [cited 2023 January 12]. Available from: 142 https://www.bdbiosciences.com/en-eu/products/reagents/flow-cytometry-reagents/research-reagents/panels-multicolor-cocktails-ruo/fitc-annexin-v-apoptosis-detection-kit-i.556547.
Wu H, Chen L, Zhu F, Han X, Sun L, Chen K. The cytotoxicity effect of resveratrol: Cell cycle arrest and induced apoptosis of breast cancer 4T1 cells. Toxins (Basel). 2019;11(12):1-20. https://doi.org/10.3390/toxins11120731
Zaitun Hasibuan PA, Rosidah, Nasution P, Ilyas S. Effect of Plectranthus amboinicus, Lour. Spreng. n-Hexane Extract on T47D Cells Line: Proliferation, Apoptosis and It’s Combination with Doxorubicine. Indones J Pharm Clin Res. 2020;3(1):8-17. https://doi.org/10.32734/idjpcr.v3i1.3323
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell. 2011;144(5):646-674. https://doi.org/10.1016/j.cell.2011.02.013.
Werfel TA, Cook RS. Efferocytosis in the tumor microenvironment. Semin Immunopathol. 2018;40(6):545-554. https://doi.org/10.1007/s00281-018-0698-5.
Hanahan D. Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022;12(1):31-46. https://doi.org/10.1158/2159-8290.CD-21-1059.
Lichota A, Gwozdzinski K. Anticancer activity of natural compounds from plant and marine environment. Int J Mol Sci. 2018;19(11):3533. https://doi.org/10.3390/ijms19113533.
Dehelean CA, Marcovici I, Soica C, et al. Plant-derived anticancer compounds as new perspectives in drug discovery and alternative therapy. Molecules. 2021;26(4):1-29. https://doi.org/10.3390/molecules26041109.
PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 289, Catechol; [cited 2023 Jan. 12]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Catechol.
Lim DY, Shin SH, Lee MH, et al. Oncotarget 35001 www.impactjournals.com/oncotarget A natural small molecule, catechol, induces c-Myc degradation by directly targeting ERK2 in lung cancer. Oncotarget. 2016;7(23):3501-3414.
Moon JY, Ediriweera MK, Ryu JY, Kim HY, Cho SK. Catechol enhances chemo- And radio-sensitivity by targeting AMPK/Hippo signaling in pancreatic cancer cells. Oncol Rep. 2021;45(3):1133-1141. https://doi.org/10.3892/or.2021.7924.
PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 5282745, 9-Hexadecenoic acid; [cited 2023 January 13]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/9-Hexadecenoic-acid.
National instituted standard and technology [Internet]. NIST Chemistry webbook, Hexadecanoic acid, ethyl ester. [Cited 2023 January 13]. Available from: https://webbook.nist.gov/cgi/cbook.cgi?InChI=1/C18H36O2/c1-3-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20-4-2/h3-17H2,1-2H3.
Millaty INK, Wijayanti N, Hidayati L, Nuringtyas TR. Identification of anticancer compounds in leaves extracts of agarwood (Aquilaria malaccensis (Lamk.)). IOP Conf Ser Earth Environ Sci. 2020;457(1):1-8. https://doi.org/10.1088/1755-1315/457/1/012036.
Nisa S, Bibi Y, Masood S, et al. Isolation, Characterization and Anticancer Activity of Two Bioactive Compounds from Arisaema flavum (Forssk.) Schott. Molecules. 2022;27:1-13. https://doi.org/10.3390/molecules27227932.
PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 442027, Ferruginol; [cited 2023 January 13]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Ferruginol.
Bispo de Jesus M, Zambuzzi WF, Ruela de Sousa RR, et al. Ferruginol suppresses survival signaling pathways in androgen-independent human prostate cancer cells. Biochimie. 2008;90(6):843-854. https://doi.org/10.1016/j.biochi.2008.01.011.
Salehi B, Quispe C, Sharifi-Rad J, et al. Phytosterols: From Preclinical Evidence to Potential Clinical Applications. Front Pharmacol. 2021;11(January):1-18. https://doi.org/10.3389/fphar.2020.599959.
PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 173183, Campesterol; [cited 2023 January 15]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Campesterol.
PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 5280794, Stigmasterol; [cited 2023 January 15]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Stigmasterol.
PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 5280794, Stigmasterol; [cited 2023 January 15]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Stigmasterol.
Alvarez-Sala A, Attanzio A, Tesoriere L, Garcia-Llatas G, Barberá R, Cilla A. Apoptotic effect of a phytosterol-ingredient and its main phytosterol (?-sitosterol) in human cancer cell lines. Int J Food Sci Nutr. 2019 May;70(3):323-334. https://doi.org/ 10.1080/09637486.2018.1511689. Epub 2018 Sep 7. PMID: 30192685.
Woyengo TA, Ramprasath VR, Jones PJH. 2009. Anticancer effects of phytosterols. Eur J Clin Nutr 63 (7): 813-820. https://doi.org/10.1038/ejcn.2009.29.
López-García G., Cilla A., Barberá R., Alegría A. (2017). Antiproliferative effect of plant sterols at colonic concentrations on Caco-2 cells. J. Funct. Foods 39, 84–90. https://doi.org/10.1016/j.jff.2017.10.006.
Endrini S, Rahmat A, Ismail P, Taufiq-Yap YH. Cytotoxic effect of ?-sitosterol from Kejibeling (Strobilanthes crispus) and its mechanism of action towards c-myc gene expression and apoptotic pathway. Med J Indones. 2014;23(4):203-208. https://doi.org/10.13181/mji.v23i4.1085.
PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 8201, Methyl stearate; [cited 2023 Jan. 24]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Methyl-stearate.
Abdel-Hady H, El-Wakil EA, Abdel-Gawad M. GC-MS Analysis, Antioxidant and Cytotoxic Activities of Mentha spicata. European J Med Plants. 2018;26(1):1-12. https://doi.org/10.9734/ejmp/2018/45751.
Hunsu VO, Facey COB, Fields JZ, Boman BM. Retinoids as chemo?preventive and molecular?targeted anti?cancer therapies. Int J Mol Sci. 2021;22(14):1-23. https://doi.org/10.3390/ijms22147731.
Zhang L, Wang J, Liu L, Zheng C, Wang Y. Synthesis and antiproliferative activity of novel all-trans-retinoic acid-podophyllotoxin conjugate towards human gastric cancer cells. Molecules. 2017;22(4):1-12. https://doi.org/10.3390/molecules22040628.
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