Journal of Multidisciplinary Applied Natural Science
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https://doi.org/10.47352/jmans.2774-3047.367
Sri Puji Astuti Wahyuningsih
Brigita Klara Krisdina Mamuaya
Firli Rahmah Primula Dewi
Lukiteswari Dyah Tri Hapsari
Baskara Wiku Adi Kusuma
Awik Puji Dyah Nurhayati
Colorectal cancer (CRC) remains the second leading cause of cancer-related mortality worldwide. Affordable herbal sources such as red okra (Abelmoschus esculentus L.) pods have gained attention as potential alternative therapies for CRC. This study aimed to evaluate the antioxidant and anticancer effects of red okra ethanol extract (ROE) using both in vitro and in vivo colorectal cancer models. The antioxidant activity of ROE was assessed using the DPPH assay, while cytotoxic activity was evaluated using the MTT assay on SW480 and HCT116 cell lines. An in vivo study was conducted using rats divided into six groups: normal control, negative control (MNU 10 mg/kg BW), positive control (MNU + methotrexate 0.08 mg/kg BW), and treatment groups receiving MNU combined with ROE at doses of 50, 100, and 200 mg/kg BW for 28 days. Serum levels of Bcl-2, COX-2, VEGF, and MMP-9 were analyzed, and histopathological evaluations of colon tissues were performed. Data were statistically analyzed using one-way ANOVA followed by Duncan’s post hoc test. Statistical significance was determined at p<0.05. ROE exhibited potent antioxidant activity (IC₅₀ = 59.66 ppm) and induced cytotoxic effects by reducing SW480 cell growth and inhibiting HCT116 cell proliferation. Moreover, ROE significantly decreased the expression of Bcl-2, COX-2, VEGF, and MMP-9. These biomarkers are associated with apoptosis inhibition, angiogenesis, inflammation, and metastasis, respectively. Histopathological analysis confirming reduced inflammatory infiltration and suppression of colon carcinogenesis. The optimal in vivo dose was 50 mg/kg BW. These findings support the development of ROE as a promising natural agent for colorectal cancer prevention and therapy.
[1] F. Bray, M. Laversanne, H. Sung, J. Ferlay, R. L. Siegel, I. Soerjomataram, and A. Jemal. (2024). "Global Cancer Statistics 2022: GLOBOCAN Estimates Of Incidence And Mortality Worldwide For 36 Cancers In 185 Countries". CA: A Cancer Journal for Clinicians. 74 (3): 229-263. 10.3322/caac.21834.
DOI: https://doi.org/10.3322/caac.21834[2] O. Uslukaya, Z. Yegin, F. Taskesen, and I. H. Yildirim. (2023). "Elevated Expression Levels Of COX-2, IL-8 And VEGF In Colon Adenocarcinoma". Cellular and Molecular Biology. 69 (6): 146-150. 10.14715/cmb/2023.69.6.22.
DOI: https://doi.org/10.14715/cmb/2023.69.6.22[3] J. H. Park, K. H. Kang, S. H. Kim, J. H. Lee, C. M. Cho, Y. O. Kweon, S. K. Kim, Y. H. Choi, H. I. Bae, and M. S. Kim. (2005). "Expression Of Cyclooxygenase-2 And Bcl-2 In Human Gastric Adenomas". The Korean Journal of Internal Medicine. 20 (3): 198-204. 10.3904/kjim.2005.20.3.198.
DOI: https://doi.org/10.3904/kjim.2005.20.3.198[4] W. H. Sun, Y. L. Sun, R. N. Fang, Y. S. Xu, H. C. Xu, Q. P. Xue, G. X. Ding, and Y. L. Cheng. (2005). "Expression Of Cyclooxygenase-2 And Matrix Metalloproteinase-9 In Gastric Carcinoma And Its Correlation With Angiogenesis". Japanese Journal of Clinical Oncology. 35 (12): 707-713. 10.1093/jjco/hyi196.
DOI: https://doi.org/10.1093/jjco/hyi196[5] H. Li, J. Yang, and F. Weng. (2024). "Growth, Physiological And Stomatal Characteristics Of Red Okra (Abelmoschus Esculentus L. Moench) Seedlings At Different Light Intensities". Pakistan Journal of Botany. 56 (3): 945-950. 10.30848/PJB2024-3(25).
[6] N. Tyagita, E. Mahati, and A. H. Safitri. (2021). "Superiority Of Purple Okra (Abelmoschus Esculentus) To Green Okra In Insulin Resistance And Pancreatic β Cell Improvement In Diabetic Rats". Folia Medica. 63 (1): 51-58. 10.3897/folmed.63.e51944.
DOI: https://doi.org/10.3897/folmed.63.e51944[7] A. K. Syam, S. Riyanti, and U. Widya. (2019). "Determination of flavonoids and polyphenols of red and green okra (Abelmoschus esculentus (L.) Moench)". Conference: Seminar Nasional Farmasi (SNIFA). 5-8.
[8] D. H. Achhlam, S. P. A. Wahyuningsih, L. D. T. Hapsari, H. Soepriandono, and F. R. P. Dewi. (2024). "Extract Of Red Okra Pod (Abelmoschus Esculentus L. Moench) Chemoprevents N-Methyl-N-Nitrosourea-Induced Kidney Proximal Tubular Cells Damage". HAYATI Journal of Biosciences. 31 (6): 1061-1070. 10.4308/hjb.31.6.1061-1070.
DOI: https://doi.org/10.4308/hjb.31.6.1061-1070[9] M. Pramudya, F. R. P. Dewi, R. W. Wong, D. W. Anggraini, D. Winarni, and S. P. A. Wahyuningsih. (2022). "Anti-Cancer Activity Of Ethanolic Extract Of Red Okra Pods (Abelmoschus Esculentus L. Moench) On Rats Induced By N-Methyl-N-Nitrosourea". Veterinary World. 15 (5): 1177-1184. 10.14202/vetworld.2022.1177-1184.
DOI: https://doi.org/10.14202/vetworld.2022.1177-1184[10] N. Nisa, S. P. A. Wahyuningsih, W. Darmanto, P. R. Purnama, F. R. P. Dewi, T. Soegiarti, and D. Karsari. (2022). "Effect Of The Ethanol Extract Of Red Okra Pods (Abelmoschus Esculentus (L.) Moench) To Inhibit Cervical Cancer Cells Growth Through Cell Cycle-Associated Oncogenes". Scientifica. 2022 : 1094771. 10.1155/2022/1094771.
DOI: https://doi.org/10.1155/2022/1094771[11] F. R. P. Dewi, S. P. A. Wahyuningsih, V. Lim, L. L. A. In, and A. Hayati. (2024). "Ethanolic Extract Of Red Okra Pods Induces Aberrant Spindle Segregation And Apoptotic Cell Death By Disrupting The Wnt Signaling Pathway In Colon Cancer Cells". Iranian Journal of Medical Sciences. 49 (12): 785-793. 10.30476/IJMS.2024.99450.3149.
[12] A. I. Faustino-Rocha, R. Ferreira, P. A. Oliveira, A. Gama, and M. Ginja. (2015). "N-Methyl-N-Nitrosourea As A Mammary Carcinogenic Agent". Tumor Biology. 36 : 9095-9117. 10.1007/s13277-015-3973-2.
DOI: https://doi.org/10.1007/s13277-015-3973-2[13] S. Deshpande. (2016). "Principles of toxicology in handbook of food toxicology". CRC Press, United States.
[14] F. R. P. Dewi, T. Domoto, M. Hazawa, A. Kobayashi, T. Douwak, T. Minamoto, and R. W. Wong. (2018). "Colorectal Cancer Cells Require Glycogen Synthase Kinase-3β For Sustaining Mitosis Via Translocated Promoter Region (TPR)-Dynein Interaction". Oncotarget. 9 (17): 13337-13352. 10.18632/oncotarget.24344.
DOI: https://doi.org/10.18632/oncotarget.24344[15] B. Tessier-Cloutier, D. D. W. Twa, M. Marzban, J. Kalina, H. J. E. Chun, N. Pavey, N. Z. Tanweer, R. L. Katz, J. J. Lum, and D. Salina. (2021). "The Presence Of Tumor-Infiltrating Neutrophils Is An Independent Adverse Prognostic Feature In Clear Cell Renal Cell Carcinoma". The Journal of Pathology: Clinical Research. 7 (4): 385-396. 10.1002/cjp2.204.
DOI: https://doi.org/10.1002/cjp2.204[16] V. S. Chedea and R. M. Pop. (2019). In: "Polyphenols in Plants: Isolation, Purification, and Extract Preparation, 2 ed". 169-183. 10.1016/B978-0-12-813768-0.00011-6.
DOI: https://doi.org/10.1016/B978-0-12-813768-0.00011-6[17] M. A. Lea, J. Pourat, R. Patel, and C. des Bordes. (2014). "Growth Inhibition Of Colon Cancer Cells By Compounds Affecting AMPK Activity". World Journal of Gastrointestinal Oncology. 6 (7): 244-252. 10.4251/wjgo.v6.i7.244.
DOI: https://doi.org/10.4251/wjgo.v6.i7.244[18] C. Ding, J. Luo, X. Fan, L. Li, S. Li, K. Wen, J. Feng, and G. Wu. (2017). "Elevated Gab2 Induces Tumor Growth And Angiogenesis In Colorectal Cancer Through Upregulating VEGF Levels". Journal of Experimental and Clinical Cancer Research. 36 (56): 1-11. 10.1186/s13046-017-0524-2.
DOI: https://doi.org/10.1186/s13046-017-0524-2[19] J. Dai, P. G. Van Wie, L. Y. Fai, D. Kim, L. Wang, P. Poyil, J. Luo, and Z. Zhang. (2016). "Downregulation Of NEDD9 By Apigenin Suppresses Migration, Invasion, And Metastasis Of Colorectal Cancer Cells". Toxicology and Applied Pharmacology. 311 : 106-112. 10.1016/j.taap.2016.09.016.
DOI: https://doi.org/10.1016/j.taap.2016.09.016[20] T. Rajakumar, P. Pugalendhi, R. Jayaganesh, D. Ananthakrishnan, and K. Gunasekaran. (2018). "Effect Of Allyl Isothiocyanate On NF-κB Signalling In 7,12-Dimethylbenz(a)anthracene And N-Methyl-N-Nitrosourea-Induced Mammary Carcinogenesis". Breast Cancer. 25 (1): 50-59. 10.1007/s12282-017-0783-y.
DOI: https://doi.org/10.1007/s12282-017-0783-y[21] N. Singh, D. Baby, J. P. Rajguru, P. B. Patil, S. S. Thakkannavar, and V. B. Pujari. (2019). "Inflammation And Cancer". Annals of African Medicine. 18 (3): 121-126. 10.4103/aam.aam_56_18.
DOI: https://doi.org/10.4103/aam.aam_56_18[22] Z. Huang, C. A. Liu, P. Z. Cai, F. P. Xu, W. J. Zhu, W. W. Wang, and H. P. Jiang. (2020). "Omega-3 PUFA Attenuates MNU-Induced Colorectal Cancer In Rats By Blocking PI3K/AKT/Bcl-2 Signaling". OncoTargets and Therapy. 13 : 1953-1965. 10.2147/OTT.S241298.
DOI: https://doi.org/10.2147/OTT.S241298[23] S. C. Tsai, C. C. Lu, C. Y. Lee, Y. C. Lin, J. G. Chung, S. C. Kuo, S. Amagaya, F. N. Chen, M. Y. Chen, F. Chan, and J. S. Yang. (2012). "AKT Serine/Threonine-Protein Kinase Modulates Bufalin-Triggered Intrinsic Pathway Of Apoptosis In CAL 27 Human Oral Cancer Cells". International Journal of Oncology. 41 (5): 1683-1692. 10.3892/ijo.2012.1605.
DOI: https://doi.org/10.3892/ijo.2012.1605[24] G. Evan. (2012). "Cancer: Taking A Back Door To Target Myc". Science. 335 (6066): 293-294. 10.1126/science.1217819.
DOI: https://doi.org/10.1126/science.1217819[25] B. A. Soliman, A. R. H. Farrag, H. A. S. Khaled, and A. A. M. Mohamed. (2018). "Combinational Effect Of 5-Fluorouracil And Resveratrol Against N-Nitroso-N-Methyl Urea-Induced Colorectal Cancer". Egyptian Journal of Hospital Medicine. 70 (6): 994-1006. 10.12816/0044352.
DOI: https://doi.org/10.12816/0044352[26] M. Szweda, A. Rychlik, I. Babińska, and A. Pomianowski. (2019). "Significance Of Cyclooxygenase-2 In Oncogenesis". Journal of Veterinary Research. 63 (2): 215-224. 10.2478/jvetres-2019-0030.
DOI: https://doi.org/10.2478/jvetres-2019-0030[27] H. Jiang and H. Li. (2021). "Prognostic Values Of Tumoral MMP2 And MMP9 Overexpression In Breast Cancer: A Systematic Review And Meta-Analysis". BMC Cancer. 21 : 149. 10.1186/s12885-021-07860-2.
DOI: https://doi.org/10.1186/s12885-021-07860-2[28] H. Hua, M. Li, T. Luo, Y. Yin, and Y. Jiang. (2011). "Matrix Metalloproteinases In Tumorigenesis: An Evolving Paradigm". Cellular and Molecular Life Sciences. 68 (23): 3853-3868. 10.1007/s00018-011-0763-x.
DOI: https://doi.org/10.1007/s00018-011-0763-x[29] S. Blanco-Prieto, L. Barcia-Castro, M. P. de la Cadena, F. J. Rodríguez-Berrocal, L. Vázquez-Iglesias, M. I. Botana-Rial, A. Fernández-Villar, and L. D. Chiara. (2017). "Relevance Of Matrix Metalloproteases In Non-Small Cell Lung Cancer Diagnosis". BMC Cancer. 17 : 823. 10.1186/s12885-017-3842-z.
DOI: https://doi.org/10.1186/s12885-017-3842-z[30] A. Valavanidis, T. Vlachogianni, K. Fiotakis, and S. Loridas. (2013). "Pulmonary Oxidative Stress, Inflammation, And Cancer: Respirable Particulate Matter, Fibrous Dust, And Ozone As Major Causes Of Lung Carcinogenesis Through Reactive Oxygen Species Mechanisms". International Journal of Environmental Research and Public Health. 10 (9): 3886-3907. 10.3390/ijerph10093886.
DOI: https://doi.org/10.3390/ijerph10093886[31] S. Das, A. Ray, N. Nasim, S. Nayak, and S. Mohanty. (2019). "Effect Of Different Extraction Techniques On Total Phenolic And Flavonoid Contents, And Antioxidant Activity Of Betel Vine, And Quantification Of Its Phenolic Constituents By Validated HPTLC Method". Biotechnology. 9 (1): 37. 10.1007/s13205-018-1565-8.
DOI: https://doi.org/10.1007/s13205-018-1565-8[32] W. Zhang, Y. Liu, and C. W. Wang. (2014). "S100A4 Promotes Squamous Cell Laryngeal Cancer Hep-2 Cell Invasion Via NF-kB/MMP-9 Signal". European Review for Medical and Pharmacological Sciences. 18 (9): 1361-1367.
[33] R. Ginwala, R. Bhavsar, D. G. I. Chigbu, P. Jain, and Z. K. Khan. (2019). "Potential Role Of Flavonoids In Treating Chronic Inflammatory Diseases With A Special Focus On The Anti-Inflammatory Activity Of Apigenin". Antioxidants. 8 (2): 35. 10.3390/antiox8020035.
DOI: https://doi.org/10.3390/antiox8020035[34] M. Heinrich, T. Dhanji, and I. Casselman. (2011). "Acai (Euterpe Oleracea Mart.) - A Phytochemical And Pharmacological Assessment Of The Species' Health Claims". Phytochemistry Letters. 4 (1): 10-21. 10.1016/j.phytol.2010.11.005.
DOI: https://doi.org/10.1016/j.phytol.2010.11.005[35] A. K. Pandurangan, P. Dharmalingam, S. K. A. Sadagopan, and S. Ganapasam. (2014). "Luteolin Inhibits Matrix Metalloproteinase 9 And 2 In Azoxymethane-Induced Colon Carcinogenesis". Human and Experimental Toxicology. 33 (11): 1176-1185. 10.1177/0960327114522502.
DOI: https://doi.org/10.1177/0960327114522502[36] C. Serafim, M. E. Araruna, E. A. Junior, M. Diniz, C. Hiruma-Lima, and L. Batista. (2020). "A Review Of The Role Of Flavonoids In Peptic Ulcer (2010–2020)". Molecules. 25 : 5431. 10.3390/molecules25225431.
DOI: https://doi.org/10.3390/molecules25225431[37] Y. Deng, S. Li, M. Wang, X. Chen, L. Tian, L. Wang, W. Yang, L. Chen, F. He, and W. Yin. (2020). "Flavonoid-Rich Extracts From Okra Flowers Exert Antitumor Activity In Colorectal Cancer Through Induction Of Mitochondrial Dysfunction-Associated Apoptosis, Senescence And Autophagy". Food & Function. 11 (12): 10448-10466. 10.1039/D0FO02081H.
DOI: https://doi.org/10.1039/D0FO02081H[38] Y. Deng, X. Huang, X. Chen, M. Wang, L. Tian, H. Zhou, W. Yang, F. He, and W. Yin. (2023). "Chemopreventive Effects Of Polysaccharides And Flavonoids From Okra Flowers In Azoxymethane/Dextran Sulfate Sodium-Induced Murine Colitis-Associated Cancer". Nutrients. 15 (22): 4820. 10.3390/nu15224820.
DOI: https://doi.org/10.3390/nu15224820[39] A. Bemidinezhad, S. A. Zojaji, S. T. Jamshidi, M. Mohammadi, M. S. Alavi, and A. Ghorbani. (2023). "Evaluation Of Acute, Subacute, And Subchronic Toxicity Of A Hepatoprotective Herbal Formulation". Toxicology Reports. 11 : 452-459. 10.1016/j.toxrep.2023.11.002.
DOI: https://doi.org/10.1016/j.toxrep.2023.11.002[40] S. I. Tertyshnyi and O. H. Chucha. (2025). "Pathomorphological Features Of Inflammatory Infiltrate In Colorectal Cancer". Pathologia. 22 (1): 12-18. 10.14739/2310-1237.2025.1.317202.
DOI: https://doi.org/10.14739/2310-1237.2025.1.317202[41] R. A. Caruso, F. Fedele, A. Parisi, D. Paparo, A. Bonanno, G. Finocchiaro, G. Branca, M. Scardigno, and L. Rigoli. (2012). "Chronic Allergic-Like Inflammation In The Tumor Stroma Of Human Gastric Carcinomas: An Ultrastructural Study". Ultrastructural Pathology. 36 (3): 139-144. 10.3109/01913123.2012.656883.
DOI: https://doi.org/10.3109/01913123.2012.656883[42] J. E. Talmadge, M. Donkor, and E. Scholar. (2007). "Inflammatory Cell Infiltration Of Tumors: Jekyll Or Hyde". Cancer and Metastasis Reviews. 26 (3-4): 373-400. 10.1007/s10555-007-9072-0.
DOI: https://doi.org/10.1007/s10555-007-9072-0[43] F. Zhang and S. Qiao. (2021). "Research Progress On The Relationship Between Inflammation And Colorectal Cancer". Annals of Gastroenterological Surgery. 6 (2): 204-211. 10.1002/ags3.12517.
DOI: https://doi.org/10.1002/ags3.12517[44] Y. Wang, L. Zhang, G. Shi, M. Liu, W. Zhao, Y. Zhang, Y. Wang, and N. Zhang. (2022). "Effects Of Inflammatory Response Genes On The Immune Microenvironment In Colorectal Cancer". Frontiers in Genetics. 13 : 886949. 10.3389/fgene.2022.886949.
DOI: https://doi.org/10.3389/fgene.2022.886949[45] F. Siddique, A. Anwaar, M. Bashir, S. Nadeem, R. Rawat, V. Eyupoglu, S. Afzal, M. Bibi, Y. A. B. Jardan, and M. Bourhia. (2024). "Revisiting Methotrexate And Phototrexate Zinc15 Library-Based Derivatives Using Deep Learning In-Silico Drug Design Approach". Frontiers in Chemistry. 12 : 1380266. 10.3389/fchem.2024.1380266.
DOI: https://doi.org/10.3389/fchem.2024.1380266[46] C. X. Ng, M. M. Affendi, P. P. Chong, and S. H. Lee. (2022). "The Potential Of Plant-Derived Extracts And Compounds To Augment Anticancer Effects Of Chemotherapeutic Drugs". Nutrition and Cancer. 74 (9): 3058-3076. 10.1080/01635581.2022.2069274.
DOI: https://doi.org/10.1080/01635581.2022.2069274[47] A. A. Wibowo, A. Sitompul, A. Yasmina, I. K. Oktaviyanti, A. Lahdimawan, and E. D. Damayanthi. (2022). "An Increase In Inflammatory Cells Related To The Increase Incidence Of Colitis And Colorectal Cancer". Bali Medical Journal. 11 (1): 499-502. 10.15562/bmj.v11i1.2842.
DOI: https://doi.org/10.15562/bmj.v11i1.2842[48] C. Xie, J. Kang, Z. Li, A. G. Schauss, T. M. Badger, S. Nagarajan, T. Wu, and X. Wu. (2012). "The Acai Flavonoid Velutin Is A Potent Anti-Inflammatory Agent: Blockade Of LPS-Mediated TNF-α And IL-6 Production Through Inhibiting NF-κB Activation And MAPK Pathway". The Journal of Nutritional Biochemistry. 23 (9): 1184-1191. 10.1016/j.jnutbio.2011.06.013.
DOI: https://doi.org/10.1016/j.jnutbio.2011.06.013[49] L. G. Monte, T. Santi-Gadelha, L. B. Reis, E. Braganhol, R. F. Prietsch, O. A. Dellagostin, R. R. E. Lacerda, C. A. A. Gadelha, F. R. Conceicao, and L. S. Pinto. (2014). "Lectin Of Abelmoschus Esculentus (Okra) Promotes Selective Antitumor Effects In Human Breast Cancer Cells". Biotechnology Letters. 36 (3): 461-469. 10.1007/s10529-013-1382-4.
DOI: https://doi.org/10.1007/s10529-013-1382-4