Indonesian Natural Compounds As Potential Anti-Colorectal Cancer Agents: A Systematic Review
Abstract
Colorectal cancer (CRC) remains a major global health burden, with increasing incidence and mortality worldwide, including in Indonesia. Natural products have long been recognized as a valuable source of anticancer agents, yet many studies on Indonesian natural resources focus on crude extracts rather than isolated compounds with defined mechanisms of action. This study aimed to systematically review isolated natural compounds derived from Indonesian biological sources with reported anti-colorectal cancer activity. A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, with literature searches performed in PubMed, SpringerLink, and ScienceDirect. Eligible studies included original experimental research investigating isolated compounds against CRC models with quantitative outcomes. A total of 16 studies were included, identifying diverse compounds from terrestrial plants, marine organisms, and propolis. Several compounds demonstrated potent cytotoxic activity, particularly in the low micromolar range, and were associated with apoptosis induction and cell cycle arrest. Mechanistic analysis revealed involvement of caspase-dependent pathways, NF-κB inhibition, and ROS-mediated apoptosis. However, many studies lacked detailed mechanistic validation and in vivo evidence. Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling indicated generally favorable pharmacokinetic properties, although potential toxicity risks and variability in absorption were observed. Overall, Indonesian natural compounds represent promising candidates for CRC therapy, but further studies are needed to improve mechanistic understanding, validate efficacy in vivo, and assess pharmacokinetic and safety profiles.
References
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Purnomo, H.D. et al., 2023. Colorectal cancer screening in Semarang, Indonesia.
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Sari, D.P., Basyuni, M., Hasibuan, P.A., Sumardi, S., Nuryawan, A., Wati, R., 2018. Cytotoxic and Antiproliferative Activity of Polyisoprenoids in Seventeen Mangroves Species Against WiDr Colon Cancer Cells. Asian Pac J Cancer Prev 19, 3393–3400. https://doi.org/10.31557/APJCP.2018.19.12.3393
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Alhawaris, A., Dengen, N., Budiman, E., Widians, J.A., Wati, M., Hairah, U., Ugiarto, M., 2023. Potency of Borneo endemic and typical plants as anti-cancer medicines. Jurnal Kimia dan Pendidikan Kimia.
Andinata, B. et al., 2023. A comparison of cancer incidences between Dharmais Cancer Hospital and GLOBOCAN 2020. Indonesian Journal of Cancer 17.
Artasasta, M.A., Yanwirasti, Y., Taher, M., Djamaan, A., Ariantari, N.P., Edrada-Ebel, R.A., Handayani, D., 2021. Apoptotic Activity of New Oxisterigmatocystin Derivatives from the Marine-Derived Fungus Aspergillus nomius NC06. Mar Drugs 19. https://doi.org/10.3390/md19110631
Atanasov, A.G., Zotchev, S.B., Dirsch, V.M., Taskforce, I.N.P.S., 2021. Natural products in drug discovery: advances and opportunities in the multi-omics era. Nature Reviews Drug Discovery.
Dong, J. et al., 2022. Can natural products be used to overcome the limitations of colorectal cancer treatment? Frontiers in Oncology 12, 884423.
Fadilah, F., Andrajati, R., Arsianti, A., Paramita, R.I., Erlina, L., Istiadi, K.A., Yanuar, A., 2023. Synthesis and in vitro Activity of Eugenyl Benzoate Derivatives as BCL-2 Inhibitor in Colorectal Cancer with QSAR and Molecular Docking Approach. Asian Pac J Cancer Prev 24, 2973–2981. https://doi.org/10.31557/APJCP.2023.24.9.2973
Han, A.-R., Kim, J.-A., Lantvit, D.D., Kardono, L.B.S., Riswan, S., Chai, H., Carcache de Blanco, E.J., Farnsworth, N.R., Swanson, S.M., Kinghorn, A.D., 2009. Cytotoxic xanthone constituents of the stem bark of Garcinia mangostana (mangosteen). J Nat Prod 72, 2028–2031. https://doi.org/10.1021/np900517h
Handayani, S., Susidarti, R.A., Jenie, R.I., Meiyanto, E., 2017. Two Active Compounds from Caesalpinia sappan L. in Combination with Cisplatin Synergistically Induce Apoptosis and Cell Cycle Arrest on WiDr Cells. Adv Pharm Bull 7, 375–380. https://doi.org/10.15171/apb.2017.045
Hardhiyuna, M., Arbi, U.Y., Zuraida, Z., Ahmadi, P., 2024. Aaptamine-rich Fraction from the Indonesian Marine Sponge, Aaptos suberitoides, Exhibits a Cytotoxic Effect on DLD-1 Colorectal Cancer Cells. Asian Pac J Cancer Prev 25, 1737–1743. https://doi.org/10.31557/APJCP.2024.25.5.1737
Huang, M., Lu, J.-J., Ding, J., 2021. Natural products in cancer therapy: past, present and future. Biomedicine & Pharmacotherapy 133, 111103.
Illian, D.N., Hafiz, I., Meila, O., Utomo, A.R.H., Nuryawan, A., Siregar, G.A., Basyuni, M., 2021. Current Status, Distribution, and Future Directions of Natural Products against Colorectal Cancer in Indonesia: A Systematic Review. Molecules 26. https://doi.org/10.3390/molecules26164984
Illian, D.N., Hasibuan, P.A.Z., Sumardi, S., Nuryawan, A., Wati, R., Basyuni, M., 2019. Anticancer Activity of Polyisoprenoids from Avicennia alba Blume. in WiDr Cells. Iran J Pharm Res 18, 1477–1487. https://doi.org/10.22037/ijpr.2019.1100719
Jiso, A., Demuth, P., Bachowsky, M., Haas, M., Seiwert, N., Heylmann, D., Rasenberger, B., Christmann, M., Dietrich, L., Brunner, T., Riyanti, Schäberle, T.F., Plubrukarn, A., Fahrer, J., 2021. Natural Merosesquiterpenes Activate the DNA Damage Response via DNA Strand Break Formation and Trigger Apoptotic Cell Death in p53-Wild-type and Mutant Colorectal Cancer. Cancers (Basel) 13. https://doi.org/10.3390/cancers13133282
Kustiawan, P.M., Lirdprapamongkol, K., Palaga, T., Puthong, S., Phuwapraisirisan, P., Svasti, J., Chanchao, C., 2017. Molecular mechanism of cardol, isolated from Trigona incisa stingless bee propolis, induced apoptosis in the SW620 human colorectal cancer cell line. BMC Pharmacol Toxicol 18, 32. https://doi.org/10.1186/s40360-017-0139-4
Kustiawan, P.M., Phuwapraisirisan, P., Puthong, S., Palaga, T., Arung, E.T., Chanchao, C., 2015. Propolis from the Stingless Bee Trigona incisa from East Kalimantan, Indonesia, Induces In Vitro Cytotoxicity and Apoptosis in Cancer Cell lines. Asian Pac J Cancer Prev 16, 6581–6589. https://doi.org/10.7314/apjcp.2015.16.15.6581
Leong, K.H., Looi, C.Y., Loong, X.-M., Cheah, F.K., Supratman, U., Litaudon, M., Mustafa, M.R., Awang, K., 2016. Cycloart-24-ene-26-ol-3-one, a New Cycloartane Isolated from Leaves of Aglaia exima Triggers Tumour Necrosis Factor-Receptor 1-Mediated Caspase-Dependent Apoptosis in Colon Cancer Cell Line. PLoS One 11, e0152652. https://doi.org/10.1371/journal.pone.0152652
Li, R., Zheng, C., Shiu, P.H.-T., Rangsinth, P., Wang, W., Kwan, Y.-W., Wong, E.S.-W., Zhang, Y., Li, J., Leung, G.P.-H., 2023. Garcinone E triggers apoptosis and cell cycle arrest in human colorectal cancer cells by mediating a reactive oxygen species–dependent JNK signaling pathway. Biomedicine & Pharmacotherapy 162, 114617. https://doi.org/10.1016/j.biopha.2023.114617
Ministry of Health of the Republic of Indonesia, 2022. Cancer Prevention and Control Framework.
Morgan, E. et al., 2023. Global burden of colorectal cancer in 2020 and 2040. Gut 72, 338–344.
Mutiah, R., Widyawaruyanti, A., Sukardiman, S., 2018. Calotroposid A: a Glycosides Terpenoids from Calotropis gigantea Induces Apoptosis of Colon Cancer WiDr Cells through Cell Cycle Arrest G2/M and Caspase 8 Expression. Asian Pac J Cancer Prev 19, 1457–1464. https://doi.org/10.22034/APJCP.2018.19.6.1457
Newman, D.J., Cragg, G.M., 2020. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. Journal of Natural Products 83, 770–803. https://doi.org/10.1021/acs.jnatprod.9b01285
Permatasanti, A., Hidayat, W., 2023. Potential of Indonesian herbal as an anti-cancer therapy. Cancer Management and Research 15, 837–850.
Purnomo, H.D. et al., 2023. Colorectal cancer screening in Semarang, Indonesia.
Rani, D.M. et al., 2023. Anti-cancer bioprospecting on medicinal plants from Indonesia. Phytochemistry.
Sari, D.P., Basyuni, M., Hasibuan, P.A., Sumardi, S., Nuryawan, A., Wati, R., 2018. Cytotoxic and Antiproliferative Activity of Polyisoprenoids in Seventeen Mangroves Species Against WiDr Colon Cancer Cells. Asian Pac J Cancer Prev 19, 3393–3400. https://doi.org/10.31557/APJCP.2018.19.12.3393
Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., Bray, F., 2021. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians 71, 209–249. https://doi.org/10.3322/caac.21660
Tang, Y.L. et al., 2023. Resistance to targeted therapy in metastatic colorectal cancer.
Xi, Y., Xu, J., 2021. Global colorectal cancer burden in 2020 and projections to 2040.
Yao, Y. et al., 2021. Serious adverse events reporting in phase III trials of colorectal cancer treatments. Frontiers in Pharmacology 12, 754858.
Yoon, D., Choi, B.-R., Shin, W.C., Kim, K.-W., Lee, Y.-S., Lee, D.Y., 2023. Metabolomics reveals that Curcuma longa and demethoxycurcumin inhibit HCT116 human colon cancer cell growth. Appl Biol Chem 66, 84. https://doi.org/10.1186/s13765-023-00844-9
Yuliana, N.D., Tuarita, M.Z., Khatib, A., Laila, F., Sukarno, S., 2020. GC-MS metabolomics revealed protocatechuic acid as a cytotoxic and apoptosis-inducing compound from black rice brans. Food Sci Biotechnol 29, 825–835. https://doi.org/10.1007/s10068-019-00725-2
Published
2026-08-08
How to Cite
FAUZI, Tio Rizki; DHARMA DEWI, Tanaya Jati; AL-JABBAR, Jauharrudin Luthfi.
Indonesian Natural Compounds As Potential Anti-Colorectal Cancer Agents: A Systematic Review.
Proceedings of International Pharmacy Ulul Albab Conference and Seminar (PLANAR), [S.l.], v. 5, p. 96-108, aug. 2026.
ISSN 2827-7848.
Available at: <https://conferences.uin-malang.ac.id/index.php/planar/article/view/3870>. Date accessed: 31 aug. 2026.
doi: https://doi.org/10.18860/planar.v5i0.3870.
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