Chemopreventive effects of Momordica charantia and Ocimum basilicum via p53 modulation in AOM-induced colon cancer

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CHRISTOPHER AKINWANDE OKELOLA
ESTHER NKECHI EZIMA
KUBURAT TEMITOPE ODUFUWA
BUKUNOLA OLUYEMISI ADEGBESAN
SEGUN BABATUNDE ABISOYE
TITOBILOLUWA CHAMPION OKELOLA

Abstract

Abstract. Okelola CA, Ezima EN, Odufuwa KT, Adegbesan BO, Abisoye SB, Okelola TC. 2025. Chemopreventive effects of Momordica charantia and Ocimum basilicum via p53 modulation in AOM-induced colon cancer. Asian J Trop Biotechnol 22: 56-63. Colon cancer is a major global health concern and is often associated with mutations in tumor suppressor genes such as p53. While chemotherapy remains the mainstay treatment, its side effects highlight the need for safer plant-based alternatives. Momordica charantia and Ocimum basilicum are medicinal plants with reported antioxidant and antiproliferative properties. This study aimed to evaluate the chemopreventive effects of aqueous extracts of these plants on azoxymethane (AOM)-induced colon carcinogenesis in rats, with emphasis on p53 modulation. Forty male Wistar rats were divided into five groups: positive control (PC, no AOM), negative control (NC, AOM only), and three treatment groups receiving AOM plus extract combinations at 50, 100, and 200 mg/kg/day for four weeks. Colon tissues were analyzed by histopathology and p53 gene expression was quantified using qRT-PCR. Phytochemical screening confirmed the presence of alkaloids, saponins, flavonoids, and phenols in both extracts. Histological evaluation showed improved mucosal architecture and reduced dysplasia in treated groups compared with NC rats. Gene expression analysis revealed that AOM exposure upregulated p53 in the NC group, indicating genotoxic stress, whereas high-dose treatment (200 mg/kg) restored p53 expression to near-normal levels. These results suggest that the combined extracts reduce DNA damage, support tissue recovery, and suppress abnormal proliferation in a dose-dependent manner. In conclusion, aqueous extracts of M. charantia and O. basilicum demonstrate significant chemoprotective effects in AOM-induced colon carcinogenesis, likely mediated through p53 modulation. This study provides preclinical evidence supporting their potential as safe, phytotherapeutic candidates for colorectal cancer prevention.

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References

Alawode O. 2013. Importance of medicinal plants in cancer therapy: A review. J Med Plant Res 7(38): 2816-2820.

AOAC. 2015. Official Methods of Analysis, 18th Edition. Association of Official Analytical Chemists, Arlington.

Arthur FKN, Woode E, Terlabi EO, Larbie C. 2011. Evaluation of acute and subchlornic toxicity of Annona muricata (Linn.) aqueous extract in animals. Eur J Exp Biol 1 (4): 115-124.

Bensaid A, Boudard F, Servent A, Morel S, Portet K, Guzman C, Vitou M, Bichon F, Poucheret P. 2022. Differential nutrition-health properties of Ocimum basilicum leaf and stem extracts. Foods 11 (12): 1699. DOI: 10.3390/foods11121699.

Bukhari SA, Farah N, Mustafa G, Mahmood S, Naqvi SAR. 2019. Magneto-priming improved nutraceutical potential and antimicrobial activity of Momordica charantia L. without affecting nutritive value. Appl Biochem Biotechnol 188 (3): 878-892. DOI: 10.1007/s12010-019-02955-w.

Chang CI, Cheng SY, Nurlatifah AO, Sung WW, Tu JH, Lee LL, Cheng HL. 2021. Bitter melon extract yields multiple effects on intestinal epithelial cells and likely contributes to anti-diabetic functions. Intl J Med Sci 18 (8): 1848-1856. DOI: 10.7150/ijms.55866.

Damasceno ROS, Pinheiro JLS, Rodrigues LHM, Gomes RC, Duarte ABS, Emídio JJ, Diniz LRL, de Sousa DP. 2024. Anti-inflammatory and antioxidant activities of eugenol (an update). Pharmaceuticals 17 (11): 1505. DOI: 10.3390/ph17111505.

Eftekhar N, Moghimi A, Mohammadian Roshan N, Saadat S, Boskabady MH. 2019. Immunomodulatory and anti-inflammatory effects of hydro-ethanolic extract of Ocimum basilicum leaves and its effect on lung pathological changes in an ovalbumin-induced rat model of asthma. BMC Complement Altern Med 19: 349. DOI: 10.1186/s12906-019-2765-4.

Ejikeme CM, Ezeonu CS, Eboatu AN. 2014. Determination of physical and phytochemical constituents of some tropical timbers indigenous to Niger Delta Area of Nigeria. Eur Sci J 10 (18): 247-270.

El Moussaoui A, Bourhia M, Jawhari FZ, Mechchate H, Slighoua M, Bari A, Ullah R, Mahmood HM, Ali SS, Ibenmoussa S, Bousta D, Bari A. 2020. Phytochemical identification, acute, and sub-acute oral toxicity studies of the foliar extract of Withania frutescens. Molecules 25 (19): 4528. DOI: 10.3390/molecules25194528.

Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F. 2020. Global Cancer Observatory: Cancer Today. International Agency for Research on Cancer, Lyon, France.

Ghodousi-Dehnavi E, Hosseini RH, Arjmand M, Nasri S, Zamani Z. 2021. A metabolomic investigation of eugenol on colorectal cancer cell line HT-29 by modifying the expression of APC, p53, and KRAS genes. Evid-based Complement Altern Med: eCAM 2021: 1448206. DOI: 10.1155/2021/1448206.

Gupta M, Sharma S, Gautam AK, Bhadauria R. 2011. Momordica charantia Linn. (Karela): Nature’s silent healer. Intl J Pharm Sci Rev Res 11: 32-37.

Gurib-Fakim A. 2006. Medicinal plants: Traditions of yesterday and drugs of tomorrow. Mol Aspects Med 27 (1): 1-93. DOI: 10.1016/j.mam.2005.07.008.

Hasbullah HH, Musa M. 2021. Gene therapy targeting p53 and KRAS for colorectal cancer treatment: A myth or the way forward? Intl J Mol Sci 22 (21): 11941. DOI: 10.3390/ijms222111941.

Islam MR, Akash S, Rahman MM, Nowrin FT, Akter T, Shohag S, Rauf Am Aljohani ASM, Simal-Gandara J. 2022. Colon cancer and colorectal cancer: Prevention and treatment by potential natural products. Chem Biol Interact 368: 110170. DOI: 10.1016/j.cbi.2022.110170.

Kandoth C, McLellan MD, Vandin F et al. 2013. Mutational landscape and significance across 12 major cancer typesr. Nature 502: 333-339. DOI: 10.1038/nature12634.

Kastenhuber ER, Lowe SW. 2017. Putting p53 in context. Cell 170 (6): 1062-1078. DOI: 10.1016/j.cell.2017.08.028.

Kisa D, Imamoglu R, Genç N, Sahin S, Qayyum MA, Elmastas M. 2021. The interactive effect of aromatic amino acid composition on the accumulation of phenolic compounds and the expression of biosynthesis-related genes in Ocimum basilicum. Physiol Mol Biol Plants 27 (9): 2057-2069. DOI: 10.1007/s12298-021-01068-1.

Klug WS, Cummings MR, Spencer CA, Palladino MA. 2018. Concepts of genetics. 11th ed. Pearson Education Inc, San Francisco.

Klug WS, Cummings MR, Spencer CA, Palladino MA. 2019. Essentials of genetics. 10th ed. Pearson Education Inc, San Francisco.

Kooti W, Daraei N, Pirouzi A, Rashi H, Asadi-Samani M, Ghadery H. 2020. Therapeutic and pharmacological potential of Ocimum basilicum L. and its main constituents: A review. Evidence-Based Complement Altern Med 2020: 1595614. DOI: 10.1155/2020/1595614.

La Torre VE, Guarniz WS, Silva-Correa C, Razco LC, Siche R. 2020. Antimicrobial activity and chemical composition of Momordica charantia: A review. Pharmacogn J 12 (1): 213–222. DOI: 10.5530/pj.2020.12.30.

Levine AJ. 2020. p53: 800 million years of evolution and 40 years of discovery. Nat Rev Cancer 20 (8): 471-480. DOI: 10.1038/s41568-020-0262-1.

Li C-J, Tsang S-F, Tsai C-H, Tsai H-Y, Chyuan J-H, Hsu H-Y. 2012. Momordica charantia extract induces apoptosis in human cancer cells through caspase- and mitochondria-dependent pathways. Evid-Based Complement Alternat Med 2012: 261971. DOI: 10.1155/2012/261971.

Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2^(-??Ct) method. Methods 25 (4): 402-408. DOI: 10.1006/meth.2001.1262.

Longley DB, Harkin DP, Johnston PG. 2003. 5-Fluorouracil: Mechanisms of action and clinical strategies. Nat Rev Cancer 3 (5): 330–338. DOI: 10.1038/nrc1074.

Minari J, Sholaja OB, Okeke U, Ayokhai J, Ojo S. 2023. Expression of cdk4 gene in MNU-induced breast cancer Wister female albino rats treated with ethanolic extract of Peperomia pellucida aerial parts: Anti-hyperplasia property of the Peperomia pellucida aerial parts extract in N-methyl-N-nitrosourea induced breast cancer of Wister female albino rat. Adv Technol 3 (1): 40-50.

Moll UM, Olivos C, Marchenko N. 2022. p53 beyond tumors: Its role in reproduction, immunity, and ageing. Nat Rev Mol Cell Biol 23(10): 625-643. DOI: 10.1038/s41580-022-00522-6.

Nadeem F, Hanif MA, Bhatti IA, Jilani MI, Al-Yahyai R. 2020. Chapter 4: Basil. In: Hanif MA, Nawaz H, Khan MM, Byrne HJ (eds). Medicinal plants of South Asia. Elsevier, Amsterdam. DOI: 10.1016/B978-0-08-102659-5.00004-5.

Omosun A, Abayomi A, Ogboye O et al. 2022. Distribution of cancer and cancer screening and treatment services in Lagos: A 10-year review of hospital records. JCO Glob Oncol 8: e2200107. DOI: 10.1200/GO.22.00107.

Ozbay T, Nahta R. 2011. Delphinidin inhibits HER2 and Erk1/2 signalling and suppresses growth of HER2 overexpressing and triple negative breast cancer cell lines. Basic Clin Res 5: 143-154. DOI: 10.4137/BCBCR.S7156.

Pietras A. 2011. Cancer stem cells in tumor heterogeneity. Adv Cancer Res 112: 255-281. DOI: 10.1016/B978-0-12-387688-1.00009-0.

Soussi T, Wiman KG. 2015. TP53: An oncogene in disguise. Cell Death Differ 22 (8): 1239-1249. DOI: 10.1038/cdd.2015.53.

Taufik RN, Pandianta A, Kusuma R, Winoto IL, Suriapratana IM, Mathew G. 2020. Pilot study for azoxymethane-induced colon cancer in male Wistar rats. Medicinus 7 (5): 120-132. DOI: 10.19166/med.v7i5.2469.

Vimala JR, Leema RA, Raja S. 2012. A study on the phytochemical analysis and corrosion inhibition on mild steel by Annona muricata L. leaves extract in 1N hydrochloric acid. Der Chemica Sinica 3 (3): 582-588.

Vousden KH, Prives C. 2022. Blinded by the light: The growing complexity of p53. Cell 185 (1): 21-36. DOI: 10.1016/j.cell.2009.04.037.

Wang S, Li Z, Yang G, Ho CT, Li S. 2017. Momordica charantia: A popular health promoting vegetable with multifunctionality. Food Funct 8 (5): 1749-1762. DOI: 10.1039/c6fo01812b.