Abstract
To identify putative antimitotic compounds, the pseudostem of banana plant (PSBP) was chosen and assays were carried out with aqueous extract of PSBP. Aqueous extract of PSBP decreased the mitotic index in onion root tips. Moreover, this extract inhibited the regeneration of blastema in amputated earthworms. Validation of this extract with MTT (3-(4, 5-dimethyl thiazolyl-2-yl)—2, 5-diphenyltetrazolium bromide) assay using MCF-7 human breast cancer cell line confirmed the presence of antimitotic activity. LC–MS analysis of this extract revealed the presence of three potential antimitotic compounds viz. α-tocotrienoxyl radical (ATT), 1,2,4-nonadecanetriol (NAT), and 3′,4′,7-trihydroxyisoflavone (THIF). Molecular docking studies suggested that these three compounds associate with α- and β-tubulin of mammalian cells and might have influenced the polymerization of microtubules. Besides, these compounds bind with active sites of cyclin-dependent kinase 2 (CDK2) protein which is required for cell division. Molecular dynamics (MD) simulation studies indicated the strong binding of THIF with α-tubulin, whereas ATT and NAT ligands with CDK2 protein. Our results clearly indicated the presence of three different antimitotic compounds from new resource and inhibit mitotic cell division. Pseudostem of banana plants could be an excellent resource for production of commercially significant antimitotic compounds.
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Abbreviations
- ATT:
-
α-Tocotrienoxyl radical
- NAT:
-
1,2,4-Nonadecanetriol
- THIF:
-
3′,4′,7-Trihydroxyisoflavone
- MTT:
-
(3-(4, 5-Dimethyl thiazolyl-2-yl)—2, 5-diphenyltetrazolium bromide)
- L1:
-
Ligand 1
- L2:
-
Ligand 2
- L3:
-
Ligand 3
- CDK2:
-
Cyclin dependent kinase 2
- MD:
-
Molecular dynamics
- PSBP:
-
Pseudostem of banana plant
References
Abdel Ghany TM, Ganash M, Alawlaqi MM, Al-Rajhi AMH (2019) Antioxidant, antitumor, antimicrobial activities evaluation of Musa paradisiaca L. pseudostem exudate cultivated in Saudi Arabia. Bionanoscience 9:172–178. https://doi.org/10.1007/s12668-018-0580-x
Amutha K, Selvakumari U (2016) Wound healing activity of methanolic stem extract of Musa paradisiaca Linn. (Banana) in Wistar albino rats. Int Wound J 13:763–767. https://doi.org/10.1111/iwj.12371
Arun KB, Madhavan A, Reshmitha TR, Nisha P (2018) Musa paradisiaca inflorescence induces human colon cancer cell death by modulating cascades of transcriptional events. In: Food and function, vol 9. Royal Society of Chemistry, pp 511–524
Beutler JA, Hamel E, Vlietinck AJ, Haemers A, Rajan P, Roitman JN, Boyd MR (1998) Structure−activity requirements for flavone cytotoxicity and binding to tubulin. J Med Chem 41:2333–2338. https://doi.org/10.1021/JM970842H
Boccardi V, Baroni M, Mangialasche F, Mecocci P (2016) Vitamin E family: role in the pathogenesis and treatment of Alzheimer’s disease. Alzheimer’s Dement Transl Res Clin Interv 2:182–191. https://doi.org/10.1016/J.TRCI.2016.08.002
Boyd MR, Paull KD (1995) Some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen. Drug Dev Res 34:91–109. https://doi.org/10.1002/ddr.430340203
Dahham SS, Mohamad TA, Tabana YM, Majid A (2015) Antioxidant activities and anticancer screening of extracts from banana fruit (Musa sapientum). Acad J Cancer Res 8:28–34. https://doi.org/10.5829/idosi.ajcr.2015.8.2.95162
Dong Z, Tian G, Xu Z, Li M, Xu M, Zhou Y, Ren H (2017) Antioxidant activities of peptide fractions derived from freshwater mussel protein using ultrasound-assisted enzymatic hydrolysis. Czech J Food Sci 35:328–338. https://doi.org/10.17221/421/2016-CJFS
El-Agamy DS, Mohamed GA, Ahmed N, Elkablawy MA, Elfaky MA, Elsaed WM, Ibrahim SR (2020) Protective anti-inflammatory activity of tovophyllin A against acute lung injury and its potential cytotoxicity to epithelial lung and breast carcinomas. Inflammopharmacology 28:153–163. https://doi.org/10.1007/S10787-019-00609-1/METRICS
Eldehna WM, Al-Rashood ST, Al-Warhi T, Eskandrani RO, Alharbi A, El Kerdawy AM (2021) Novel oxindole/benzofuran hybrids as potential dual CDK2/GSK-3β inhibitors targeting breast cancer: design, synthesis, biological evaluation, and in silico studies. J Enzyme Inhib Med Chem 36:270–285. https://doi.org/10.1080/14756366.2020.1862101/SUPPL_FILE/IENZ_A_1862101_SM8866
Kalpana S, Nirmaladevi R, Shrinidhi-Rai R, Karthika P (2013) Inhibition of calcium oxalate crystallization in vitro by extract of banana cultivar monthan. Int J Pharm Pharm Sci 5(4):649–653
Kamaraj R (2019) Earthworm, an in vivo system to screen proliferative and antimitotic compounds. Int J Innov Technol Explor Eng 9:677–682. https://doi.org/10.35940/ijitee.b1164.1292s219
Kundu L, Ray S (2017) Mitotic abnormalities and micronuclei inducing potentials of colchicine and leaf aqueous extracts of Clerodendrum viscosum Vent. in Allium cepa root apical. Caryologia 70:7–14. https://doi.org/10.1080/00087114.2016.1254452
Laetitia G, Sven S, Fabrice J (2020) Combinatorial therapies in thyroid cancer: an overview of preclinical and clinical progresses. Cells 9:830
Lee JH, Lee HJ (2013) A daidzein metabolite, 6,7,4′-trihydroxyisoflavone inhibits cellular proliferation through cell cycle arrest and apoptosis induction in MCF10CA1a human breast cancer cells. J Korean Soc Appl Biol Chem 56:695–700. https://doi.org/10.1007/s13765-013-3164-z
Lee DE, Lee KW, Song NR, Seo SK, Heo YS, Kang NJ, Dong Z (2010) 7,3′,4′-Trihydroxyisoflavone inhibits epidermal growth factor-induced proliferation and transformation of JB6 P+ mouse epidermal cells by suppressing cyclin-dependent kinases and phosphatidylinositol 3-kinase *. J Biol Chem 285:21458–21466. https://doi.org/10.1074/JBC.M109.094797
Lee DE, Lee KW, Jung SK, Lee EJ, Hwang JA, Lim TG, Dong Z (2011) 6,7,4′-Trihydroxyisoflavone inhibits HCT-116 human colon cancer cell proliferation by targeting CDK1 and CDK2. Carcinogenesis 32:629–635. https://doi.org/10.1093/CARCIN/BGR008
Lin S, Li Q, Xu Z, Chen Z, Tao Y, Tong Y, Wang P (2022) Detection of the role of intestinal flora and tryptophan metabolism involved in antidepressant-like actions of crocetin based on a multi-omics approach. Psychopharmacology 239:3657–3677. https://doi.org/10.1007/S00213-022-06239-W/METRICS
Lo S, Leung E, Fedrizzi B, Barker D (2021) Syntheses of mono-acylated luteolin derivatives, evaluation of their antiproliferative and radical scavenging activities and implications on their oral bioavailability. Sci Rep 11:1–9. https://doi.org/10.1038/s41598-021-92135-w
Nadana GRV, Rajesh C, Kavitha A, Sivakumar P, Sridevi G, Palanichelvam K (2020) Induction of growth and defence mechanism in rice plants towards fungal pathogen by eco-friendly coelomic fluid of earthworm. Environ Technol Innov 19:101011. https://doi.org/10.1016/j.eti.2020.101011
Oberlies NH, Rogers LL, Martin JM, McLaughlin JL (1998) Cytotoxic and insecticidal constituents of the UnripeFruit of Persea americana. J Nat Prod 61:781–785. https://doi.org/10.1021/NP9800304
Peng YH, Shiao HY, Tu CH, Liu PM, Hsu JTA, Amancha PK, Wu SY (2013) Protein kinase inhibitor design by targeting the Asp-Phe-Gly (DFG) motif: the role of the DFG motif in the design of epidermal growth factor receptor inhibitors. J Med Chem 56:3889–3903. https://doi.org/10.1021/JM400072P/SUPPL_FILE/JM400072P_SI_001.PDF
Raj MH, Ghosh D, Banerjee R, Salimath BP (2017) Suppression of VEGF-induced angiogenesis and tumor growth by Eugenia jambolana, Musa paradisiaca, and Coccinia indica extracts. Pharm Biol 55:1489–1499. https://doi.org/10.1080/13880209.2017.1307422
Rajamanikkam K, Elaiya Raja S, Balaji SK, Rajavadivu GN, Sivasubramaniam S, Palanichelvam K (2019) Earthworm, a novel in vivo system to validate antimitotic compounds. Turk J Zool 43:153–163. https://doi.org/10.3906/zoo-1806-36
Rajesh C, Palanimuthu VR, Palanichelvam K (2021) Fatty acids and its derivatives of Acorus calamus Linn. rhizome induce stem cell-mediated cell division in plants and animals. Biocatal Agric Biotechnol 36:102153. https://doi.org/10.1016/j.bcab.2021.102153
Ranasinghe R, Mathai M, Zulli A (2022) A synopsis of modern—day colorectal cancer: where we stand. Biochim Biophys Acta Rev Cancer 1877:188699. https://doi.org/10.1016/J.BBCAN.2022.188699
Ravelli RBG, Gigant B, Curmi PA, Jourdain I, Lachkar S, Sobel A, Knossow M (2004) Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature 428:198–202. https://doi.org/10.1038/nature02393
Rimbach G, Moehring J, Huebbe P, Lodge JK (2010) Gene-regulatory activity of α-tocopherol. Molecules 15:1746–1761. https://doi.org/10.3390/MOLECULES15031746
Romijn JC, Verkoelen CF, Schroeder FH (1988) Application of the MTT assay to human prostate cancer cell lines in vitro: establishment of test conditions and assessment of hormone-stimulated growth and drug-induced cytostatic and cytotoxic effects. Prostate 12:99–110. https://doi.org/10.1002/PROS.2990120112
Sadh PK, Duhan S, Duhan JS (2018) Agro-industrial wastes and their utilization using solid state fermentation: a review. Bioresour Bioprocess 5:1
Sivasubramaniam S (2021) The earthworm Eudrilus Eugeniae: a model organism for regenerative biology. Genet Genom Sci 6:1–4. https://doi.org/10.24966/ggs-2485/100023
Trott O, Olson AJ (2009) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. https://doi.org/10.1002/jcc.21334
Whittaker SR, Mallinger A, Workman P, Clarke PA (2017) Inhibitors of cyclin-dependent kinases as cancer therapeutics. Pharmacol Ther 173:83–105. https://doi.org/10.1016/J.PHARMTHERA.2017.02.008
Wu S-J, Ng L-T (2010) Tocotrienols inhibited growth and induced apoptosis in human HeLa cells through the cell cycle signaling pathway. Integr Cancer Ther 9:66–72. https://doi.org/10.1177/1534735409357757
Yesudhason BV, Kanniah P, Subramanian ER, Ponesakki V, Rajendiran V, Sivasubramaniam S (2018) Exploiting the unique phenotypes of the earthworm Eudrilus eugeniae to evaluate the toxicity of chemical substances. Environ Monit Assess 190:1–14. https://doi.org/10.1007/S10661-018-6477-X
Zhang Y, Li H, Zhang J, Zhao C, Lu S, Qiao J, Han M (2020) The combinatory effects of natural products and chemotherapy drugs and their mechanisms in breast cancer treatment. Phytochem Rev 19:1179–1197
Zhang M, Zhang L, Hei R, Li X, Cai H, Wu X, Cai C (2021) CDK inhibitors in cancer therapy, an overview of recent development. Am J Cancer Res 11:1913–1935
Acknowledgements
The seed money provided to this research by the Kalasalingam Academy of Research and Education [KARE], Krishnankoil, Tamil Nadu, India is greatly acknowledged. Mr. C. Rajesh, Mr. KS. Balaji and Dr. R. Prakash are grateful to KARE for the research fellowship received.
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Rajesh, C., Sahoo, S., Balaji, S.K. et al. Three compounds from banana pseudostem inhibit mitotic cell division by interacting with tubulin and cyclin-dependent kinase 2 proteins: in vivo, in vitro and in silico approach. J. Plant Biochem. Biotechnol. 33, 56–67 (2024). https://doi.org/10.1007/s13562-023-00861-1
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DOI: https://doi.org/10.1007/s13562-023-00861-1