Dysobinol Extracted from Chisocheton Macrophyllus Triggers Proliferation Inhibition, Potential Apoptosis, and Cell Cycle Arrest of He La Cancer Cell Lines

Shabarni Gaffar, Ersanda Hafiz, Hesti Lina Wiraswati, Safri Ishmayana, Nurlelasari Nurlelasari


Dysobinol is a new limonoid from C. macrophyllus seeds reported to have an anticancer activity. This study aimed to determine the cytotoxic activity of Dysobinol against HeLa cancer cell lines and evaluate its mechanism of action by determining the expression level of several carcinogenesis genes related to apoptosis and cell cycle. In this experimental study, the cytotoxic activity was determined using the MTS assay and gene expression by real-time reverse transcriptase PCR. The result shows that Dysobinol has an anticancer activity in a dose and time-dependent manner against HeLa cells and was categorized as toxic with IC50 values of 52.92, 52.70, and 14.96 μg/ml for 24, 48, and 72 hours, respectively. Dysobinol significantly increased the expression of Bax, Cas-8, and Cas-3 and decreased the expression of Cyc D1 at both doses (IC50 and 2x IC50) but only high doses (2x IC50) could affect Cas9 and NF-κB expressions, indicating that Dysobinol can induce apoptosis via the extrinsic pathway and inhibits the cell cycle through the Cyc D1 regulator. Dysobinol has the potential to be developed as a chemotherapy drug or an adjuvant agent for cervical cancer treatment.


Apoptosis, cell cycle arrest, cytotoxic activity, dysobinol, HeLa cell line

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  1. Perera WPRT, Liyanage JA, Dissanayake KGC, Gunathilaka H, Weerakoon WMTDN, Wanigasekara DN, et al. Antiviral potential of selected medicinal herbs and their isolated natural products. Biomed Res Int. 2021;7872406:1–18.
  2. Happi GM, Nangmo PK, Dzouemo LC, Kache SF, Kouam ADK, Wansi JD. Contribution of Meliaceous plants in furnishing lead compounds for antiplasmodial and insecticidal drug development. J Ethnopharmacol. 2022;285:114906.
  3. Shilpi JA, Saha S, Chong SL, Nahar L, Sarker SD, Awang K. Advances in chemistry and bioactivity of the genus Chisocheton Blume. Chem Biodiv. 2016;13(5):483–503.
  4. Nurlelasari N, Katja DG, Harneti D, Wardayo MM, Supratman U, Awang K. Limonoids from the seeds of Chisocheton macrophyllus. Chem Nat Comp. 2017;53(1):83–7.
  5. Zhang Y, Xu H. Recent progress in the chemistry and biology of limonoids. Royal Soc. of Chem. Adv. 2017;7(56):35191–220.
  6. Chen J, Fan X, Zhu J, Song L, Li Z, Lin F, et al. Limonoids from seeds of Azadirachta indica A. Juss. and their cytotoxic activity. Acta Pharmaceutica Sinica B. 2018;8(4):639–44.
  7. Maneerat W, Laphookhieo S, Koysomboon S, Chantrapromma K. Antimalarial, antimycobacterial, and cytotoxic limonoids from Chisocheton siamensis. Phytomed 2008;15(12):1130–4.
  8. Mohamad K, Hirasawa Y, Litaudon M, Awang K, Hadi AHA, Takeya K, Ekasari W, Widyawaruyanti A, Zaini NC, Morita H. Ceramicines B–D, New antiplasmodial limonoids from Chisocheton ceramicus. Bioorg Med Chem. 2009;17(2):727–30.
  9. Inada A, Somekawa M, Murata H, Nakanishi T, Takuda H, Nishino S, et al. Phytochemical studies on Meliaceous plants. VIII. Structures and inhibitory effects on Epstein-barr virus activation of triterpenoids from leaves of Chisocheton macrophyllus King. Chem Pharm Bull. 1993;41(3):617–19.
  10. Chong SL, Hematpoor A, Hazni H, Sofian-Azirun M, Lioudon M, Supratman U, Murata M, Awang K. Mosquito Larvacidal limonoids from the fruits of Chisocheton Erythrocarpus Hiern. Phytochem Lett. 2019;30:69–73.
  11. Bordoloi M, Saikia B, Mathur RK, Goswami BN. A Meliacin from Chisocheton panniculatus. Phytochem. 1993;34(2):583–84.
  12. Yang MH, Wang JG, Luo JG, Wang XB, Kong LY. Chisopanins A-K, 11 new Protolimonoids from Chisocheton paniculatus and their anti-inflammatory activities. Bioorg Med Chem, 2011;19(4):1409–17.
  13. Tasyriq M, Najmuldeen IA, In LLA, Mohamad K, Awang K, Hasima N. 7α-hydroxy-β-sitosterol from Chisocheton tomentosus induces apoptosis via dysregulation of cellular Bax/Bcl-2 ratio and cell cycle arrest by downregulating ERK1/2 activation. Evid Based Complement Alternat Med. 2012;12(2):1–12.
  14. Wong CP, Kaneda T, Hadi AHA, Morita H. Ceramicine B, A limonoid with anti-lipid droplets accumulation activity from Chisocheton ceramicus. J Nat Med. 2014;68(1):22–30.
  15. Braicu C, Buse M, Busuioc C, Drula R, Gulei D, Raduly L, Rusu A, Irimie A, Atanasov AG, Slaby O, Ionescu C, Berindan-Neagoe I. A comprehensive review on MAPK: A promising therapeutic target in cancer. Cancers (Basel). 2019;11(10):1618:1–25.
  16. Gondhowiardjo S, Christina N, Ganapati NPD, Hawariy S, Radityamurti F, Jayalie VF, et al. Five-year cancer epidemiology at the National Referral Hospital: Hospital-based cancer registry data in Indonesia. JCO Glob Oncol. 2021;7:190–203.
  17. Aubrey BJ, Kelly GL, Janic A, Herald MJ, Strasser A. How does p53 induce apoptosis, and how does this relate to p53-mediated tumor suppression? Cell Death Differ. 2018;25:104–113.
  18. Chimento A, De Luca A, D’Amico M, De Amicis F, Pezzi V. The involvement of natural polyphenols in molecular mechanisms inducing apoptosis in tumor cells: A promising adjuvant in cancer therapy. Int J Mol Sci. 2023;24(2):1680.
  19. Pecorino L. Molecular Biology of Cancer: Mechanisms, Targets, and Therapeutics, Oxford University Press, 5rd ed. 2021. p. 149–60.
  20. Phadwal K, Tang QY, Luijten I, Zhao JF, Corcoran B, Semple RK, Ganley IG, MacRae VE. p53 regulates mitochondrial dynamics in vascular smooth muscle cell calcification. Int J Mol Sci. 2023;13;24(2):1643.
  21. Poladian N, Orujyan D, Narinyan W, Oganyan AK, Navasardyan I, Velpuri P, Chorbajian A, Venketaraman V. Role of NF-κB during Mycobacterium tuberculosis Infection. Int J Mol Sci. 2023;24(2):1772.
  22. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real time quantitative PCR and the 2-ΔΔCT method. Methods. 2001;25:402–8.
  23. Venkata KCN, Rathinavelu A, Bishayee A. Chapter 11-Limonoids: structure-activity relationship studies and anticancer properties. Studies Nat Prod Chem. 2019;59:375–99.
  24. Chakravorty A, Sugden B. Long-distance communication: Looping of human papillomavirus genomes regulates expression of viral oncogenes. PLoS Biol. 2018; 16(11):e3000062.1–7.
  25. Wen N, Bian L, Gong J, Meng Y. Overexpression of cell-cycle related and expression-elevated protein in tumor (CREPT) in malignant cervical cancer. J Int Med Res. 2020;48(1):1–7.
  26. Jun SY, Kim J, Yoon N, Maeng LS, Byun JH. Prognostic potential of cyclin D1 expression in colorectal cancer. J Clin Med. 2023:10;12(2):572.
  27. Mandapati A, Lukong KE. Triple negative breast cancer: approved treatment options and their mechanisms of action. J Cancer Res Clin Oncol. 2022;1–19.

DOI: https://doi.org/10.15395/mkb.v56.3249

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