Abstract
Natural products in conjunction with computer-aided drug design have made a significant impact in the development of novel therapeutics in a fast manner in modern-day drug discovery. Spondia mombin has been reported among locals to be effective in the management of colon cancer. Hence, this study was conducted to experimentally justify the anti-tumor properties of Spondia mombin amongst locals using the combination of benchtop cytotoxicity [Ranicep ranninus (RR) and Saccharomyces cerevisiae (SC)] and human HCT 116 colon cancer cell line (Sulfordiamine B assay) as well as computational chemistry models. The crude extract (CSM) and an aqueous fraction of S. mombin (ASM) at 20–100 µg/mL showed 80–100% mortality of RR, while 7.81–250 µg/mL of CSM and ASM also exhibited 70–95% cytotoxic effect of SC. A 2.02% increase in cytotoxic effect on colorectal cancer cell line (human HCT 116) was observed in ASM (IC50—22.23 ± 2.56 µg/mL) relative to 21.78 ± 2.98 µg/mL observed in CSM. Gramisterol, campesterol, chalinasterol, obtusifoliol, beta-sitosterol, stigmasterol, and betulin isolated from CSM (from literature) were shown to possess steroidal scaffold, they were observed to show promising anti-colon cancer properties via antagonistic influence on epidermal growth factor receptor, vascular endothelial growth factor receptor, and mammalian target of rapamycin colon receptors through van der Waal, alkyl, carbon-hydrogen, conventional hydrogen, and pi-alkyl interactions with the amino acid residues in the binding sites of the receptors. Findings from this research experimentally justify the ethnopharmacological claim of S. mombin in the treatment of colon cancer via antagonist polypharmacological action of the steroidal compounds on different receptors implicated in colon cancer carcinogenesis.
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Abdul-Hammed M, Adedotun IO, Olajide M et al (2022) Virtual screening, ADMET profiling, PASS prediction, and bioactivity studies of potential inhibitory roles of alkaloids, phytosterols, and flavonoids against COVID-19 main protease (Mpro). Nat Prod Res. https://doi.org/10.1080/14786419.2021.1935933
Adedokun MO, Oladoye AO, Oluwalana SA, Mendie II (2010) Socio-economic importance and utilization of Spondias mombin in Nigeria. Asian Pac J Trop Med. https://doi.org/10.1016/S1995-7645(10)60015-6
Adedokun O, Ntungwe EN, Viegas C et al (2022) Enhanced anticancer activity of hymenocardia acida stem bark extract loaded into PLGA nanoparticles. Pharmaceuticals. https://doi.org/10.3390/ph15050535
Akindele AJ, Wani ZA, Sharma S et al (2015) In vitro and in vivo anticancer activity of root extracts of sansevieria liberica gerome and labroy (agavaceae). Evid-Based Complement Altern Med. https://doi.org/10.1155/2015/560404
Aoyagi T, Terracina KP, Raza A, Takabe K (2014) Current treatment options for colon cancer peritoneal carcinomatosis. World J Gastroenterol 20:124
Ayinde BA, Agbakwuru U (2010) Cytotoxic and growth inhibitory effects of the methanol extract Struchium sparganophora Ktze (Asteraceae) leaves. Pharmacogn Mag. https://doi.org/10.4103/0973-1296.71795
Bakchi B, Krishna AD, Sreecharan E et al (2022) An overview on applications of SwissADME web tool in the design and development of anticancer, antitubercular and antimicrobial agents: a medicinal chemist’s perspective. J Mol Struct 1259:132712
Barnes J (2010) Trease and Evans’ pharmacognosy. Focus Altern Complement Ther. https://doi.org/10.1111/j.2042-7166.1999.tb01062.x
Bhowmik R, Roy S, Sengupta S, Sharma S (2021) Biocomputational and pharmacological analysis of phytochemicals from zingiber officinale (Ginger), allium sativum (garlic), and murrayakoenigii (curry leaf) in contrast to type 2-diabetes. Int J Appl Pharm. https://doi.org/10.22159/ijap.2021v13i5.42294
Bintari YR, Risandiansyah R (2019) In silico study to assess antibacterial activity from Cladophora Sp. on peptide deformylase: molecular docking approach. Borneo J Pharm. https://doi.org/10.33084/bjop.v2i1.717
Biosci IJ, Rubiaceae JESEAB, Oise IE et al (2014) Comparative phytochemical, cytototic and growth inhibitory effects of the leaf and root barks of Sarcocephalus Latifolius (J.E. Smith) E.A. Bruce (Rubiaceae). Int J Biosci 6655:162–169. https://doi.org/10.12692/ijb/4.4.162-169
Bitencourt-Ferreira G, de Azevedo WF (2019) Docking with SwissDock
Chopra I, Li HF, Wang H, Webster KA (2012) Phosphorylation of the insulin receptor by AMP-activated protein kinase (AMPK) promotes ligand-independent activation of the insulin signalling pathway in rodent muscle. Diabetologia. https://doi.org/10.1007/s00125-011-2407-y
da Silva Lima EG, da Silva AtaÃde WL, da Costa AS, Silva KRS, Maltarolo BM, Costa TC, da Costa RCL, de Souza LC, Okumura RS (2016) Nitrogenous compounds in hog plum plants (Spondia mombin L.) under water deficit. Afr J Agric Res. https://doi.org/10.5897/ajar2015.10552
Drago L (2019) Probiotics and colon cancer. Microorganisms. https://doi.org/10.3390/microorganisms7030066
Evans WC (2002) Trease and evans pharmacognosy, 15th edn. Saunders, Edinburgh
Ferrer FA, Miller LJ, Andrawis RI et al (1998) Angiogenesis and prostate cancer: in vivo and in vitro expression of angiogenesis factors by prostate cancer cells. Urology. https://doi.org/10.1016/S0090-4295(97)00491-3
Gbolade AA, Adedokun OA, Okotie OO et al (2019) Anti-proliferative and cytotoxic activities of Heliconia psittacorum L. f (Heliconiaceae) and Ficus coronata Spin. (Moraceae) leaves. J Pharm Bioresour. https://doi.org/10.4314/jpb.v16i1.6
Ikpefan EO, Ayinde BA, Mudassar BA, Farooq AD (2020) Anticancer and antioxidant studies of the methanol extract and fractions of Conyza sumatrensis (retz) E. H. Walker (asteraceae). Niger J Nat Prod Med. https://doi.org/10.4314/njnpm.v23i1.10
Imran M, Aslam Gondal T, Atif M et al (2020) Apigenin as an anticancer agent. Phyther. Res. 34:1812–1828
Isah T (2016) Anticancer alkaloids from trees: development into drugs. Pharmacogn Rev 10:90–99. https://doi.org/10.4103/0973-7847.194047
Loughrey MB, Coleman HG (2018) Aspirin, statins and molecular pathological epidemiology of colon cancer. J Pathol 246:S9
McGuire S (2016) International agency for research on cancer. World Health Organizarion. World cancer report 2014. World cancer Report 2014. Adv Nutr 7
Mustafi R, Dougherty U, Shah H et al (2012) Both stromal cell and colonocyte epidermal growth factor receptors control HCT116 colon cancer cell growth in tumor xenografts. Carcinogenesis. https://doi.org/10.1093/carcin/bgs231
Mvondo JGM, Matondo A, Mawete DT et al (2021) In silico ADME/T properties of quinine derivatives using SwissADME and pkCSM webservers. Int J Trop Dis Health. https://doi.org/10.9734/ijtdh/2021/v42i1130492
Najib A, Handayani V, Ahmad AR, Hikmat S (2019) Insilico screening chemical compounds α-glucosidase inhibitor from cordia myxa L. Int J Res Pharm Sci. https://doi.org/10.26452/ijrps.v10i3.1419
Nduche MU, Omosun G (2016) The use of medicinal plants in the treatment of diarrhoea in Nigeria : ethnomedical inventory of Abia State. Sch J Agric Vet Sci 3:270–274
Ohiagu FO, Chikezie PC, Chikezie CM, Enyoh CE (2021) Anticancer activity of Nigerian medicinal plants: a review. Future J Pharm Sci. https://doi.org/10.1186/s43094-021-00222-6
Oluwasegun A, Ume O, Nasiru A et al (2019) Evaluation of antidiabetic and anti-lipid peroxidation potentials of leaves crude and solvent fractions of Annona Muricata Linn (Annonaceae). J Pharmacogn Phytochem 8:3973–3977
Oso BJ, Adeoye AO, Olaoye IF (2022) Pharmacoinformatics and hypothetical studies on allicin, curcumin, and gingerol as potential candidates against COVID-19-associated proteases. J Biomol Struct Dyn. https://doi.org/10.1080/07391102.2020.1813630
Roberto A, Caetano PP (2005) A high-throughput screening method for general cytotoxicity part I chemical toxicity. Método rápido para triagem da citotoxicidade geral parte I Toxicidade química 1 1
Rudraswamy S, Godhi B, Shankar HJ et al (2021) Detailed understanding of different extraction methods for the research on medicinal plants. Indian J Oral Health Res. https://doi.org/10.4103/ijohr.ijohr_3_21
Stoffel EM, Murphy CC (2020) Epidemiology and mechanisms of the increasing incidence of colon and rectal cancers in young adults. Gastroenterology. https://doi.org/10.1053/j.gastro.2019.07.055
Taieb J, Gallois C (2020) Adjuvant chemotherapy for stage iii colon cancer. Cancers (basel) 12:2679
Verma D, Mitra D, Paul M et al (2021) Potential inhibitors of SARS-CoV-2 (COVID 19) proteases PLpro and Mpro/3CLpro: molecular docking and simulation studies of three pertinent medicinal plant natural components. Curr Res Pharmacol Drug Discov. https://doi.org/10.1016/j.crphar.2021.100038
Vichai V, Kirtikara K (2006) Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc 1:1112–1116. https://doi.org/10.1038/nprot.2006.179
Vogel VG, McPherson RS (1989) Dietary epidemiology of colon cancer. Hematol Oncol Clin N Am 3:35–63
Zhu H, Dougherty U, Robinson V et al (2011) EGFR signals downregulate tumor suppressors miR-143 and miR-145 in western diet-promoted murine colon cancer: role of G 1 regulators. Mol Cancer Res. https://doi.org/10.1158/1541-7786.MCR-10-0531
Acknowledgements
This research work was carried out by collective effort, scientific skills, financial input of AO, UO, OO, under the supervision of AO. Special appreciations to Igbinedion University, Okada, Nigeria for the provision of laboratory space, equipment, chemicals and expertise for the successful actualization of this research.
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Adedokun Oluwasegun has no conflict of interest. Ume Ogochukwu has no conflict of interest. Ogunniran Olusewa has no conflict of interest.
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Oluwasegun, A., Ogochukwu, U. & Olusewa, O. Unveiling the polypharmacology mechanistic role of steroidal scaffolds from Spondia mombin L. (Anacardiaceae) on EGFR, VEGF, and mTOR: validation of usage in colorectal cancer management in Southwestern Nigeria. ADV TRADIT MED (ADTM) 24, 305–322 (2024). https://doi.org/10.1007/s13596-023-00700-7
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DOI: https://doi.org/10.1007/s13596-023-00700-7