Published July 15, 2024 | Version v1
Journal article Open

Molecular mechanism elucidation of Ocimum basilicum as anticancer using system bioinformatic approach supported by in vitro assay

Authors/Creators

  • 1. National Research and Innovation Agency, Bogor, Indonesia
  • 2. National Research and Innovation Agency, Bogor, Indonesia|Universitas Indonesia, Depok, Indonesia
  • 3. Universitas Indonesia, Depok, Indonesia

Description

Breast cancer (BC) is a multifactorial disease involving many pathways and target molecules. Multi-target therapy through multi-compound herbal medicines is an alternative strategy to treat BC. In the present study, we elucidate the molecular mechanism of Ocimum basilicum (OB) as an anticancer agent using system bioinformatic approach and investigate its cytotoxic effect against MCF-7 cells. We performed network pharmacology (NP) and molecular docking studies to provide scientific information regarding the underlying anti-BC mechanism of OB. Based on topology parameters obtained from protein-protein interaction (PPI), we identified six potential targets that play a significant role in the network including SRC, PI3KCA, EGFR, ESR1, AKT1, and MAPK1. Furthermore, consensus docking suggested rutin, quercetin-3-O-diglucoside, and kaempferol-3-O-β-D-rutinoside as the potential compounds of OB. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the cytotoxic effect of OB might be related to the modulation of several pathways such as PI3K-Akt, VEGF, and HIF-1, breast cancer, and estrogen signaling pathways. The in vitro assay revealed that various extracts of OB demonstrated cytotoxic effects against MCF-7 with IC50 = 231 µg/mL (OB ethanolic extract), 408 µg/mL (OB methanolic extract), 479 µg/mL (OB ethyl acetate extract), 1887 µg/mL (OB n-hexanoic extract) and 767 µg/mL (OB butanolic extract) respectively.

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Cites
Publication: 10.3897/pharmacia.70.e103478 (DOI)
Publication: 10.3923/pjbs.2013.1744.1750 (DOI)
Publication: 10.3389/fphar.2021.805391 (DOI)
Publication: 10.1016/j.breast.2022.08.010 (DOI)
Publication: 10.2174/1570180811007010726 (DOI)
Publication: 10.5772/intechopen.89669 (DOI)
Publication: 10.1002/9780470015902.A0028845 (DOI)
Publication: 10.1016/j.phyplu.2021.100212 (DOI)
Publication: 10.1016/j.yexcr.2010.09.001 (DOI)
Publication: 10.1016/j.biopen.2016.09.004 (DOI)
Publication: 10.1186/s12906-023-04058-w (DOI)
Publication: 10.1016/j.gendis.2018.05.001 (DOI)
Publication: 10.2174/092986708783503212 (DOI)
Publication: 10.1021/ci300399w (DOI)
Publication: 10.4161/cbt.12.8.16907 (DOI)
Publication: 10.1677/jme.1.01846 (DOI)
Publication: 10.1080/07391102.2015.1070749 (DOI)
Publication: 10.1007/s11030-019-09924-9 (DOI)
Publication: 10.1074/jbc.M116.772426 (DOI)
Publication: 10.2147/DDDT.S257494 (DOI)
Publication: 10.1016/j.molstruc.2022.133627 (DOI)
Publication: 10.1186/s12906-018-2153-5 (DOI)
Publication: 10.1021/ci1002679 (DOI)
Publication: 10.1021/ci3003057 (DOI)
Publication: 10.1016/j.compbiolchem.2023.107907 (DOI)
Publication: 10.1007/s10863-018-9750-3 (DOI)
Publication: 10.1016/j.bmc.2015.08.006 (DOI)
Publication: 10.3978/j.issn.2072-1439.2010.02.03.9 (DOI)
Publication: 10.1016/j.phymed.2022.154268 (DOI)
Publication: 10.3390/ph16010004 (DOI)
Publication: 10.1016/j.biopha.2022.112616 (DOI)
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Figure: 10.3897/pharmacia.71.e127395.figure3 (DOI)
Figure: 10.3897/pharmacia.71.e127395.figure5 (DOI)
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Figure: 10.3897/pharmacia.71.e127395.figure1 (DOI)
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Figure: 10.3897/pharmacia.71.e127395.figure4 (DOI)

References

  • Agustini K, Kusumaningrum S, Firdayani, Sulfanti A, Wink M (2023) Estrogenic activity of Bryonia dioica Jacq. through in silico and in vitro studies on pS2 gene expression in the breast cancer cell line MCF-7. Pharmacia 70(4): 951–958. https://doi.org/10.3897/pharmacia.70.e103478
  • Al-Ali KH, El-Beshbishy HA, El-Badry AA, Alkhalaf M (2013) Cytotoxic activity of methanolic extract of Mentha longifolia and Ocimum basilicum against human breast cancer. Pakistan Journal of Biological Sciences 16(23): 1744–1750. https://doi.org/10.3923/pjbs.2013.1744.1750
  • Aminian AR, Mohebbati R, Boskabady MH (2022) The effect of Ocimum basilicum L. and its main ingredients on respiratory disorders: An experimental, preclinical, and clinical review. Frontiers in Pharmacology 12: 805391. https://doi.org/10.3389/fphar.2021.805391
  • Arnold M, Morgan E, Rumgay H, Mafra A, Singh D, Laversanne M, Vignat J, Gralow JR, Cardoso F, Siesling S, Soerjomataram I (2022) Current and future burden of breast cancer: Global statistics for 2020 and 2040. Breast 66: 15–23. https://doi.org/10.1016/j.breast.2022.08.010
  • Arshad Qamar K, Dar A, Siddiqui BS, Kabir N, Aslam H, Ahmed S, Erum S, Habib S, Begum S (2010) Anticancer activity of Ocimum basilicum and the effect of ursolic acid on the cytoskeleton of MCF-7 human breast cancer cells. Letters in Drug Design & Discovery 7(10): 726–736. https://doi.org/10.2174/1570180811007010726
  • Baktiar Laskar Y, Meitei Lourembam R, Behari Mazumder P (2020) Herbal remedies for breast cancer prevention and treatment, IntechOpen. https://doi.org/10.5772/intechopen.89669
  • Bolognesi ML, Rossi M (2020) Multitarget Drug Discovery. Encyclopedia of Life Sciences 1–7. https://doi.org/10.1002/9780470015902.A0028845
  • Charles-Okhe O, Odeniyi MA, Fakeye TO, Ogbole OO, Akinleye TE, Adeniji AJ (2022) Cytotoxic activity of crude extracts and fractions of African peach (nauclea latifolia smith) stem bark on two cancer cell lines. Phytomedicine Plus 2(1): 1–9. https://doi.org/10.1016/j.phyplu.2021.100212
  • de Diesbach MT, Cominelli A, N'Kuli F, Tyteca D, Courtoy PJ (2010) Acute ligand-independent Src activation mimics low EGF-induced EGFR surface signalling and redistribution into recycling endosomes. Experimental Cell Research 316(19): 3239–3253. https://doi.org/10.1016/j.yexcr.2010.09.001
  • Eanes L, Patel YM (2016) Inhibition of the MAPK pathway alone is insufficient to account for all of the cytotoxic effects of naringenin in MCF-7 breast cancer cells. Biochimie Open 3: 64–71. https://doi.org/10.1016/j.biopen.2016.09.004
  • Eid AM, Jaradat N, Shraim N, Hawash M, Issa L, Shakhsher M, Nawahda N, Hanbali A, Barahmeh N, Taha B, Mousa A (2023) Assessment of anticancer, antimicrobial, antidiabetic, anti-obesity and antioxidant activity of Ocimum Basilicum seeds essential oil from Palestine. BMC Complementary Medicine and Therapies 23(1): 221. https://doi.org/10.1186/s12906-023-04058-w
  • Feng Y, Spezia M, Huang S, Yuan C, Zeng Z, Zhang L, Ji X, Liu W, Huang B, Luo W, Liu B, Lei Y, Du S, Vuppalapati A, Luu HH, Haydon RC, He TC, Ren G (2018) Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes & Diseases 5(2): 77–106. https://doi.org/10.1016/j.gendis.2018.05.001
  • Giordano S, Petrelli A (2008) From single- to multi-target drugs in cancer therapy: When aspecificity becomes an advantage. Current Medicinal Chemistry 15(5): 422–432. https://doi.org/10.2174/092986708783503212
  • Houston DR, Walkinshaw MD (2013) Consensus docking: improving the reliability of docking in a virtual screening context. Journal of Chemical Information and Modeling 53(2): 384–390. https://doi.org/10.1021/ci300399w
  • Irwin ME, Bohin N, Boerner JL (2011) Src family kinases mediate epidermal growth factor receptor signaling from lipid rafts in breast cancer cells. Cancer Biology & therapy 12(8): 718–726. https://doi.org/10.4161/cbt.12.8.16907
  • Kim JH, Lee MH, Kim BJ, Kim JH, Han SJ, Kim HY, Stallcup MR (2005) Role of aspartate 351 in transactivation and active conformation of estrogen receptor α. Journal of Molecular Endocrinology 35(3): 449–464. https://doi.org/10.1677/jme.1.01846
  • Li J, Zhou N, Liu W, Li J, Feng Y, Wang X, Wu C, Bao J (2016) Discover natural compounds as potential phosphodiesterase-4B inhibitors via computational approaches. Journal of Biomolecular Structure & Dynamics 34(5): 1101–1112. https://doi.org/10.1080/07391102.2015.1070749
  • Mahajan P, Wadhwa B, Barik MR, Malik F, Nargotra A (2020) Combining ligand- and structure-based in silico methods for the identification of natural product-based inhibitors of Akt1. Molecular Diversity 24(1): 45–60. https://doi.org/10.1007/s11030-019-09924-9
  • Maheshwari S, Miller MS, O'Meally R, Cole RN, Amzel LM, Gabelli SB (2017) Kinetic and structural analyses reveal residues in phosphoinositide 3-kinase α that are critical for catalysis and substrate recognition. Journal of Biological Chemistry 292(33): 13541–13550. https://doi.org/10.1074/jbc.M116.772426
  • Makhoba XH, Viegas C, Mosa RA, Viegas FPD, Pooe OJ (2020) Potential impact of the multi-target drug approach in the treatment of some complex diseases. Drug Design, Development and Therapy 14: 3235–3249. https://doi.org/10.2147/DDDT.S257494
  • Nguyen TK, Nguyen TNL, Nguyen K, Nguyen HVT, Tran LTT, Ngo TXT, Pham PTV, Tran MH (2022) Machine learning-based screening of MCF-7 human breast cancer cells and molecular docking analysis of essential oils from Ocimum basilicum against breast cancer. Journal of Molecular Structure 1268: 133627. https://doi.org/10.1016/j.molstruc.2022.133627
  • Nordin ML, Abdul Kadir A, Zakaria ZA, Abdullah R, Abdullah MNH (2018) In vitro investigation of cytotoxic and antioxidative activities of Ardisia crispa against breast cancer cell lines, MCF-7 and MDA-MB-231. BMC Complementary Medicine and Therapies 18(1): 87. https://doi.org/10.1186/s12906-018-2153-5
  • Sabbah DA, Vennerstrom JL, Zhong H (2010) Docking studies on isoform-specific inhibition of phosphoinositide-3 kinases. Journal of Chemical Information and Modeling 50(10): 1887–1898. https://doi.org/10.1021/ci1002679
  • Sabbah DA, Vennerstrom JL, Zhong HA (2012) Binding selectivity studies of phosphoinositide 3-kinases using free energy calculations Journal of Chemical Information and Modeling 52(12): 3213–3224. https://doi.org/10.1021/ci3003057
  • Sangande F, Agustini K, Budipramana K (2023) Antihyperlipidemic mechanisms of a formula containing Curcuma xanthorrhiza, Sechium edule, and Syzigium polyanthum: In silico and in vitro studies. Computational Biology and Chemistry 105: 107907. https://doi.org/10.1016/j.compbiolchem.2023.107907
  • Torres RG, Casanova L, Carvalho J, Marcondes MC, Costa SS, Sola-Penna M, Zancan P (2018) Ocimum basilicum but not Ocimum gratissimum present cytotoxic effects on human breast cancer cell line MCF-7, inducing apoptosis and triggering mTOR/Akt/p70S6K pathway. Journal of Bioenergetics and Biomembranes 50(2): 93–105. https://doi.org/10.1007/s10863-018-9750-3
  • Xing L, Klug-Mcleod J, Rai B, Lunney EA (2015) Kinase hinge binding scaffolds and their hydrogen bond patterns. Bioorganic & Medicinal Chemistry 23(19): 6520–6527. https://doi.org/10.1016/j.bmc.2015.08.006
  • Xu YL, Sun Q (2010) Headway in resistance to endocrine therapy in breast cancer. Journal of Thoracic Disease 2(3): 171–177. https://doi.org/10.3978/j.issn.2072-1439.2010.02.03.9
  • Yang HY, Liu ML, Luo P, Yao XS, Zhou H (2022) Network pharmacology provides a systematic approach to understanding the treatment of ischemic heart diseases with traditional Chinese medicine. Phytomedicine 104: 154268. https://doi.org/10.1016/j.phymed.2022.154268
  • Youssef AMM, Maaty DAM, Al-Saraireh YM (2022) Phytochemistry and anticancer effects of mangrove (Rhizophora mucronata Lam.) leaves and stems extract against different cancer cell lines. Pharmaceuticals 16(1): 4. https://doi.org/10.3390/ph16010004
  • Zhang T, Zhou H, Wang K, Wang X, Wang M, Zhao W, Xi X, Li Y, Cai M, Zhao W, Xu Y, Shao R (2022) Role, molecular mechanism and the potential target of breast cancer stem cells in breast cancer development. Biomedicine & pharmacotherapy 147: 112616. https://doi.org/10.1016/j.biopha.2022.112616