Author(s):
Syamsurizal, Diah Tri Utami, Sutrisno
Email(s):
syamsurizal68@unja.ac.id
DOI:
10.52711/0974-360X.2026.00332 
Address:
Syamsurizal1*, Diah Tri Utami1, Sutrisno2
1Department of Pharmacy, Faculty of Medicine and Health Sciences, Universitas Jambi, Indonesia.
2Department of Chemistry, Faculty of Science and Technology, Universitas Jambi, Indonesia.
*Corresponding Author
Published In:
Volume - 19,
Issue - 5,
Year - 2026
ABSTRACT:
The cytotoxic activity of Cyrtostachys renda bioactive substances was recently investigated in vitro. C. renda was macerated with methanol to extract its four groups of fractions (C, E, K, and O), which were then separated using column chromatography. Each component was qualitatively identified in its fraction content and assessed in vitro for its cytotoxic properties in HeLa, MCF-7, T47D, and Vero cells. The most active fraction was further evaluated for its synergistic effect in co-chemotherapy with doxorubicin against HeLa cells. Each fraction dose-dependently inhibited the growth of HeLa, MCF-7, and T47D cells. Fraction O had the highest cytotoxic activity, as indicated by the IC50 value of 112 µg/mL against HeLa cells, with a selectivity index of 7.70. Fraction O, with a concentration of 28 µg/mL, also showed synergistic activity with doxorubicin 2.8 µg/mL in inhibiting the growth of HeLa cells. Fraction O induces cell cycle arrest at the G1 and G2/M phases, as well as apoptosis in HeLa cells. Furthermore, cell necrosis might be reduced by combining the effects of fraction O at 28 µg/mL and doxorubicin at 2.8 µg/mL. Fraction O, a natural chemotherapeutic drug that requires further development for cancer management, was introduced by our findings.
Cite this article:
Syamsurizal, Diah Tri Utami, Sutrisno. Antiproliferative Activity and Synergistic Effect of Fractions of Cyrtostachys renda and Doxorubicin Against Human Cancer Cells. Research Journal Pharmacy and Technology. 2026;19(5):2310-8. doi: 10.52711/0974-360X.2026.00332
Cite(Electronic):
Syamsurizal, Diah Tri Utami, Sutrisno. Antiproliferative Activity and Synergistic Effect of Fractions of Cyrtostachys renda and Doxorubicin Against Human Cancer Cells. Research Journal Pharmacy and Technology. 2026;19(5):2310-8. doi: 10.52711/0974-360X.2026.00332 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2026-19-5-53
REFERENCES:
1. Cao, W., Qin, K., Li, F., Chen, W. Comparative study of cancer profiles between 2020 and 2022 using global cancer statistics (Globocan). Journal of The National Cancer Center. 2024; 4(2), 128–134. doi.org/10.1016/j.jncc.2024.05.001.
2. Li, L., Shan, T., Zhang, D., Ma, F. Nowcasting and forecasting global aging and cancer burden: Analysis of data from the Globocan and global burden of disease study. Journal of the National Cancer Center. 2024; 4(3): 223–232. doi.org/10.1016/j.jncc.2024.05.002.
3. Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., Jemal, A. Global cancer statistics 2022: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2024; 74(3): 229–263. doi.org/10.3322/caac.21834.
4. Dhakad, G. G., Nannaware, M. S., Wagh, G. V., Shrirao, A. V., Kochar, N. I., Chandewar, A. V. Review on medicinal use of pumpkin seed on human health. Research Journal of Pharmacology and Pharmacodynamics. 2023; 15(2): 59–65. doi.org/10.52711/2321-5836.2023.00012.
5. Patial, A., Kumar, P., Sunita, Dhiman, A., Kumar, P. Herbal medicine used in cancer treatment. Research Journal of Pharmacognosy and Phytochemistry. 2023; 15(1): 33–38. doi.org/10.52711/0975-4385.2023.00006.
6. Cranbrook, E. Key environments: Malaysia. Elsevier, England. 1988. doi.org/10.1016/C2009-0-11009-7.
7. Peng, W., Liu, Y.-J., Wu, N., Sun, T., He, X.-Y., Gao, Y.-X., Wu, C.-J. Areca catechu L. (Arecaceae): A review of its traditional uses, botany, phytochemistry, pharmacology and toxicology. Journal of Ethnopharmacology. 2025; 164: 340–356. doi.org/10.1016/j.jep.2015.02.010.
8. Salehi, B., Konovalov, D. A., Fru, P., Kapewangolo, P., Peron, G., Ksenija, M. S., Cardoso, S. M., Pereira, O. R., Nigam, M., Nicola, S., Pignata, G., Rapposelli, S., Sestito, S., Anil Kumar, N. V., de la Luz Cádiz-Gurrea, M., Segura-Carretero, A., P. Mishra, A., Sharifi-Rad, M., Cho, W. C., Sharifi-Rad, J. Areca catechu from farm to food and biomedical applications. Phytotherapy Research. 2020; 34(9): 2140–2158. https://doi.org/10.1002/ptr.6665.
9. Syamsurizal, Sutrisno, Utami, D. T. Cytotoxic activity of Cyrtostachys renda extracts and fractions against MCF-7 and HeLa cancer cells through cell cycle arrest and apoptosis induction mechanism. Journal of Advanced Pharmaceutical Technology and Research. 2025; 16(1): 18. doi.org/10.4103/JAPTR.JAPTR_222_24.
10. Syamsurizal, S., Utami, D. T., Sutrisno, S., Efrini, E., Jumardi, M. I. Toxicity test of red palm (Cyrtostachys renda blume.) using the brine shrimp lethality test (BSLT) method. Journal of Pharmaceutical and Sciences. 2023; 1(1): 407–413. doi.org/10.36490/journal-jps.com.v6i5-si.429.
11. Syamsurizal, S., Utami, D. T. The combination of fraction A3 of Cyrtostachys renda Blume with doxorubicin improved cytotoxicity against T47D cell line through cell cycle arrest and apoptotic induction. Journal of Applied Pharmaceutical Science. 2024; 14(09): 270-278. doi.org/10.7324/JAPS.2024.173607.
12. Shanthi, D., Saravanan, R. Evaluation of cytotoxicity of normal Vero and anticancer activity of human breast cancer cell lines by aqueous unripe fruit extract of Solanum torvum. Research Journal of Pharmacy and Technology. 2021; 14(7): 3504–3508. doi.org/10.52711/0974-360X.2021.00607.
13. Utami, D. T., Nugraheni, N., Jenie, R. I., Meiyanto, E. Co-treatment of brazilein enhances cytotoxicity of doxorubicin on WiDr colorectal cancer cells through cell cycle arrest. The Indonesian Biomedical Journal. 2020; 12(4). doi.org/10.18585/inabj.v12i4.1293.
14. Tesfay T, Tekluu B, K KC, Lakkamraju DV, Palleti JD, Rai S, Kamalakararao K. In vitro Anticancer activity of Rumex abyssinicus root extracts on breast cancer MCF-7 cell lines. Research Journal of Pharmacy and Technology. 2023; 16(11): 5410-5. doi: 10.52711/0974-360X.2023.00876.
15. Ahmad, G. M., Serie, M. M. A., Ghoneem, T., Ghareeb, D. A., Yacout, G. A., Abdel-Latif, M. S. Apoptotic-antiproliferative activity of Salix mucronata and Triticum spelta against human breast, lung, and liver cancer cells: a comparative study with other plant extracts containing phenolics and flavonoids. South African Journal of Botany. 2024; 171: 788–801. doi.org/10.1016/j.sajb.2024.06.033.
16. Jothi, J. M., Jayaprakash, A. Phytochemical analysis and in vitro anticancer activity of Enteromorpha compressa against ovarian cancer. Research Journal of Pharmacy and Technology. 2022; 15(5): 1943–1947. doi.org/10.52711/0974-360X.2022.00323.
17. Kendre, N., Wakte, P. LC-MS/MS-QTOF screening and identification of phenolic compounds from ethyl acetate fraction of Madhuca longifolia leaves. Research Journal of Pharmacy and Technology. 2024; 17(4): 1434–1440. doi.org/10.52711/0974-360X.2024.00227.
18. Alalhareth, I. S., Alyami, S. M., Alshareef, A. H., Ajeibi, A. O., Al Munjem, M. F., Elfifi, A. A., Alsharif, M. M., Alzahrani, S. A., Alqaad, M. A., Bakir, M. B., Abdel-Wahab, B. A. Cellular epigenetic targets and epidrugs in breast cancer therapy: Mechanisms, challenges, and future perspectives. Pharmaceuticals. 2025; 18(2). doi.org/10.3390/ph18020207.
19. Chirakkara, S. P., George, J., Abraham, A. Mice ovarian microbiome investigation divulges prospective fount of anticancer and antimicrobial metabolites. Research Journal of Pharmacy and Technology. 2023; 16(10): 4847–4854. doi.org/10.52711/0974-360X.2023.00786.
20. Serini, S., Calviello, G. Potential of natural phenolic compounds against doxorubicin-induced chemobrain: biological and molecular mechanisms involved. Antioxidants. 2024; 13(4). doi.org/10.3390/antiox13040486.
21. Vladu, A. F., Ficai, D., Ene, A. G., Ficai, A. Combination therapy using polyphenols: An efficient way to improve antitumoral activity and reduce resistance. International journal of molecular sciences. 2022; 23(18). doi.org/10.3390/ijms231810244.
22. Oršolić, N., Jembrek, M. J. Potential strategies for overcoming drug resistance pathways using propolis and its polyphenolic/flavonoid compounds in combination with chemotherapy and radiotherapy. Nutrients. 2024; 16(21): 3741. doi.org/10.3390/nu16213741.
23. Sen, A., Kumar, K., Khan, S., Pathak, P., Singh, A. Current therapy in cancer: Advances, challenges, and future directions. Asian Journal of Nursing Education and Research. 2024: 14(1): 77–84. doi.org/10.52711/2349-2996.2024.00016.
24. Asnaashari, S., Amjad, E., Sokouti, B. Synergistic effects of flavonoids and paclitaxel in cancer treatment: A systematic review. Cancer Cell International. 2023; 23(1). doi.org/10.1186/s12935-023-03052-z.
25. Mitra, S., Tareq, A. M., Das, R., Emran, T. B., Nainu, F., Chakraborty, A. J., Ahmad, I., Tallei, T. E., Idris, A. M., Simal-Gandara, J. Polyphenols: A first evidence in the synergism and bioactivities. Food Reviews International. 2023; 39(7): 4419–4441. doi.org/10.1080/87559129.2022.2026376.
26. Zhang, T., Li, N., Wang, R., Sun, Y., He, X., Lu, X., Chu, L., Sun, K. Enhanced therapeutic efficacy of doxorubicin against multidrug-resistant breast cancer with reduced cardiotoxicity. Drug Delivery. 2023; 30(1): 2189118. doi.org/10.1080/10717544.2023.2189118.
27. Radeva, L., Yordanov, Y., Spassova, I., Kovacheva, D., Tzankova, V., Yoncheva, K. Double-loaded doxorubicin/resveratrol polymeric micelles providing low toxicity on cardiac cells and enhanced cytotoxicity on lymphoma cells. Pharmaceutics. 2023; 15(4). doi.org/10.3390/pharmaceutics15041287.
28. Aristiani, W., Desvita, W. R., Khayatulisma, D., Edityaningrum, C. A., Guntarti, A., Nurani, L. H. Enhancing anticancer potential: investigating the synergistic impact of doxorubicin and curcumin on HeLa and Vero cells in vitro. Journal of Food and Pharmaceutical Sciences. 2024; 12(1): 52–60. doi.org/10.22146/jfps.10887.
29. Prabhu, K. S., Kuttikrishnan, S., Ahmad, N., Habeeba, U., Mariyam, Z., Suleman, M., Bhat, A. A., Uddin, S. H2AX: A key player in DNA damage response and a promising target for cancer therapy. Biomedicine and Pharmacotherapy. 2024; 175: 116663. doi.org/10.1016/j.biopha.2024.116663.
30. Abdel-Malek, A. R., Moustafa, A. Y., Salem, S. H. Antimicrobial and cytotoxic activities of flavonoid and phenolics extracted from Sepia pharaonis ink (Mollusca: Cephalopoda). BMC Biotechnology. 2024; 24(1). doi.org/10.1186/s12896-024-00880-3.
31. Tubtimsri, S., Chuenbarn, T., Manmuan, S. Quercetin triggers cell apoptosis-associated ROS-mediated cell death and induces S and G2/M-phase cell cycle arrest in kon oral cancer cells. BMC Complementary Medicine and Therapies. 2025; 25(1). doi.org/10.1186/s12906-025-04782-5.
32. Srivastava, M., Pant, A. B. Environmental stressors-mediated apoptosis and autophagy detected through flow cytometry. In Flow Cytometry: Applications in Cellular and Molecular Toxicology. 2025; 49–79. Springer, Singapore. https://doi.org/10.1007/978-981-97-9758-5_4.
33. Singaravelan, N., Tollefsbol, T. O. Polyphenol-based prevention and treatment of cancer through epigenetic and combinatorial mechanisms. Nutrients. 2025; 17(4): 616. doi.org/10.3390/nu17040616.
34. Raza, W., Meena, A., Luqman, S. Diosmetin: A dietary flavone as modulator of signaling pathways in cancer progression. molecular Carcinogenesis. 2024; 63(9): 1627–1642. doi.org/10.1002/mc.23774.
35. Shahjahan, S., Naraharisetti, L. T., Begum, A., Yakkala, P. A., Lakshmi Soukya, P. s., Godugu, C., Begum, S. A., Kamal, A. Oxindoline containing thiazolidine-4-one tethered triazoles act as antimitotic agents by targeting microtubule dynamics. Chemistry Select. 2024; 9(17): e202400539. doi.org/10.1002/slct.202400539.
36. Batool, S., Asim, L., Qureshi, F. R., Masood, A., Mushtaq, M., Saleem, R. S. Z. Molecular targets of plant-based alkaloids and polyphenolics in liver and breast cancer- an insight into anticancer drug development. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2025; 25(5): 295–312. doi.org/10.2174/0118715206302216240628072554.
37. Ragunathan A, Ravi L, Krishnan K. Anticancer Cytotoxic Activity of Pentane-2,4-dione extracted from the Leaves of Cordia sebestena. Research Journal of Pharmacy and Technology. 2018; 11(6): 2191-2196. doi: 10.5958/0974-360X.2018.00405.5.
38. Wang, S., Guo, S., Guo, J., Du, Q., Wu, C., Wu, Y., Zhang, Y. Cell death pathways: Molecular mechanisms and therapeutic targets for cancer. MedComm. 2024; 5(9): e693. doi.org/10.1002/mco2.693.
39. Ojo, O. A., Nwafor-Ezeh, P. I., Rotimi, D. E., Iyobhebhe, M., Ogunlakin, A. D., Ojo, A. B. Apoptosis, inflammation, and oxidative stress in infertility: A mini review. Toxicology Reports. 2023; 10: 448–462. doi.org/10.1016/j.toxrep.2023.04.006.
40. Korbecki, J., Bosiacki, M., Kupnicka, P., Barczak, K., Ziętek, P., Chlubek, D., Baranowska-Bosiacka, I. Biochemistry and diseases related to the interconversion of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. International Journal of Molecular Sciences. 2024; 25(19). doi.org/10.3390/ijms251910745.
41. Christidi, E., Brunham, L. R. Regulated cell death pathways in doxorubicin-induced cardiotoxicity. Cell Death and Disease. 2021; 12(4): 1–15. doi.org/10.1038/s41419-021-03614-x.
42. Liu, Q., Du, P., Zhu, Y., Zhang, X., Cai, J., Zhang, Z. Thioredoxin reductase 3 suppression promotes colitis and carcinogenesis via activating pyroptosis and necrosis. Cellular and Molecular Life Sciences. 2022; 79(2): 1–14. doi.org/10.1007/s00018-022-04155-y.
43. Dhakad, G. G., Shirsat, S. P., Tambe, K. P. Review on immuno-oncology agents for cancer therapy. Research Journal of Pharmacology and Pharmacodynamics. 2022; 14(1): 47–52. doi.org/10.52711/2321- 5836.2022.00008.
44. Pang, H., Huang, G., Xie, Z., Zhou, Z. The Role of regulated necrosis in diabetes and its complications. Journal of Molecular Medicine. 2024; 102(4): 495–505. doi.org/10.1007/s00109-024-02421-z.
45. Hu, J., Liu, Y., Du, Y., Peng, X., Liu, Z. Cellular organelles as drug carriers for disease treatment. Journal of Controlled Release. 2023; 363: 114–135. doi.org/10.1016/j.jconrel.2023.09.038.
46. Guo, J., Yang, W., Mai, F., Liang, J., Luo, J., Zhou, M., Yu, D., Wang, Y., Li, C. Unravelling oncosis: Morphological and molecular insights into a unique cell death pathway. Frontiers in Immunology. 2024;15. doi.org/10.3389/fimmu.2024.1450998.
47. Lai, Y., Zhang, T., Huang, L., Klymchenko, A. S., Lin, W. An exchangeable sim probe for monitoring organellar dynamics of necrosis cells and intracellular water heterogeneity in kidney repair. Proceedings of the National Academy of Sciences. 2025; 122(1): e2402348121. doi.org/10.1073/pnas.2402348121.
48. Trybus, W., Trybus, E., Obarzanowski, M., Król, T. Quinalizarin induces autophagy, apoptosis and mitotic catastrophe in cervical and prostate cancer cells. Scientific Reports. 2025; 15(1): 5252. doi.org/10.1038/s41598-025-89847-8.