Exploring Squalene and Rhodoxanthin from Hylocereus undatus as a Therapeutic Agent for the Treatment of Human Liver Cancer using Docking Analysis

  • Padmavathy K Research Scholar, Department of Zoology, Presidency College, Chennai, India.
  • Sivakumari K Associate Professor, Department of Zoology, Presidency College, Chennai, India.
  • Rajesh S Research Scholar, Department of Zoology, Presidency College, Chennai, India.
Keywords: Dragon Fruit, Squalene, Rhodoxanthin, Apoptotic Proteins, Liver Cancer


Introduction: The dragon fruit H. undatus contains several active phyto-compounds, which act as good antioxidant, anti-inflammatory, and anti-cancer agents. To explore the apoptotic potential of these phyto-compounds, it would be apt to screen the interaction of these compounds with apoptotic proteins via., in silico docking studies.
Method: The current study was planned to evaluate the docking interaction of selected GC-MS spectrum components from H. undatus (squalene and rhodoxanthin) with apoptotic proteins (AIF, Apaf-1, BAK, caspase 8, and RIP) by PatchDock docking algorithm.
Results: The docking interaction showed that rhodoxanthin docks well with apoptotic proteins, and rhodoxanthin is recommended by the Lipinski rule as the best treatment for liver cancer.
Conclusion: The application of rhodoxanthin as a potential and natural therapeutic agent to cure diseases is validated by docking results.

How to cite this article:
Padmavaty K, Sivakumari K, Rajesh S. Exploring Squalene and Rhodoxanthin from Hylocereus undatus as a Therapeutic Agent for the Treatment of Human Liver Cancer using Docking Analysis. Chettinad Health City Med J. 2022;11(2):24-32.

DOI: https://doi.org/10.24321/2278.2044.202213


Sanghani HV, Ganatra SH, Pande R. Molecular - docking studies of potent anticancer agent. J Comput Sci Syst Biol. 2012;5:12-5. [Google Scholar]

Ullah A, Prottoy NI, Araf Y, Hossain S, Sarkar B, Saha A. Molecular docking and pharmacological property analysis of phytochemicals from Clitoria ternatea as potent inhibitors of cell cycle checkpoint proteins in the cyclin/cdk pathway in cancer cells. Comput Mol Biosci. 2019;9(3):81-94. [Google Scholar]

Schneidman-Duhovny D, Nussinov R, Wolfson HJ. Predicting molecular interactions in silico: II. Protein-protein and protein-drug docking. Curr Med Chem. 2004;11(1):91-107. [PubMed] [Google Scholar]

Zoete V, Grosdidier A, Michielin O. Docking, virtual high throughput screening and in silico fragment-based drug design. J Cell Mol Med. 2009;13(2):238-48. [PubMed] [Google Scholar]

Phillips MA, Stewart MA, Woodling DL, Xie ZR. Has molecular docking ever brought us a medicine? In: Vlachakis DP, editor. Molecular docking. London: Intech Open; 2018. [Google Scholar]

Padmavathy K, Sivakumari K, Karthika S, Rajesh S, Ashok K. A study on phytochemical profiling and anticancer activity of dragon fruit Hylocereus undatus (Haworth) extracts against human hepatocellular carcinoma cancer (HepG-2) cell line. Int J Pharm Sci Res. 2021;12(5):2770-8.

Yuriev E, Ramsland PA. Latest developments in molecular docking: 2010-2011 in review. J Mol Recognit. 2013;26(5):215-39. [PubMed] [Google Scholar]

Hubbard RE, Haider MK. Hydrogen bonds in proteins: role and strength. In: Encyclopedia of Life Sciences (ELS). Chichester: John Wiley and Sons Ltd; 2010. p. 1-7. [Google Scholar]

Hudon J, Derbyshire D, Leckie S, Flinn T. Diet-induced plumage erythrism in Baltimore Orioles as a result of the spread of introduced shrubs. Wilson J Ornithol. 2013;125:88-96. [Google Scholar]

Britton G, Khachik F. Carotenoids in food. In: Britton G, Liaaen-Jensen S, Pfander H, editors. Carotenoids: nutrition and health. Vol. 5. Birkhäuser Verlag: Basel; 2009. p. 55-7. [Google Scholar]

Pérez-Gálvez A, Viera I, Roca M. Carotenoids and chlorophylls as antioxidants. Antioxidants. 2020;9:505. [PubMed] [Google Scholar]

Nishino H, Tokuda H, Murakoshi M, Satomi Y, Masuda M, Onozuka M, Yamaguchi S, Takayasu J, Tsuruta J, Okuda M, Khachik F, Narisawa T, Takasuka N, Yano M. Cancer prevention by natural carotenoids. Biofactors. 2000;13(1-4):89-94. [PubMed] [Google Scholar]

Ihara T, Yamamoto T, Sugamata M, Okumura H, Ueno Y. The process of ultrastructural changes from nuclei to apoptotic body. Virchows Arch. 1998;433(5):443-7. [PubMed] [Google Scholar]

Gregory CD, Devitt A. The macrophage and the apoptotic cell: an innate immune interaction viewed simplistically? Immunology. 2004;113(1):1-14. [PubMed] [Google Scholar]

Savill J, Fadok V. Corpse clearance defines the meaning of cell death. Nature. 2000;407(6805):784-8. [PubMed] [Google Scholar]

Kurosaka K, Takahashi M, Watanabe N, Kobayashi Y. Silent cleanup of very early apoptotic cells by macrophages. J Immunol. 2003;171(9):4672-9. [PubMed] [Google Scholar]

Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J. Human ICE/CED-3 protease nomenclature. Cell. 1996;87(2):171. [PubMed] [Google Scholar]

Nicholson DW, Thornberry NA. Caspases: killer proteases. Trends Biochem Sci. 1997;22(8):299-306. [PubMed] [Google Scholar]

Hotchkiss RS, Nicholson DW. Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol. 2006;6(11):813-22. [PubMed] [Google Scholar]

Budihardjo I, Oliver H, Lutter M, Luo X, Wang X. Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol. 1999;15:269-90. [PubMed] [Google Scholar]

Matsuyama S, Llopis J, Deveraux QL, Tsien RY, Reed JC. Changes in intramitochondrial and cytosolic pH: early events that modulate caspase activation during apoptosis. Nat Cell Biol. 2000;2(6):318-25. [PubMed] [Google Scholar]

Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science. 1998;281(5381):1305-8. [PubMed] [Google Scholar]

Igney FH, Krammer PH. Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer. 2002;2(4):277-88. [PubMed] [Google Scholar]

Fulda S, Debatin KM. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene. 2006;25(34):4798-11. [PubMed] [Google Scholar]

Mousavi SH, Tayarani-Najaran Z, Hersey P. Apoptosis: from signalling pathways to therapeutic tools. Iran J Basic Med Sci. 2008;11(3):121-42. [Google Scholar]

Saelens X, Festjens N, Walle LV, van Gurp M, van Loo G, Vandenabeele P. Toxic proteins released from mitochondria in cell death. Oncogene. 2004;23(16):2861-74. [PubMed] [Google Scholar]

Garrido C, Galluzzi L, Brunet M, Puig PE, Didelot C, Kroemer G. Mechanisms of cytochrome c release from mitochondria. Cell Death Differ. 2006;13(9):1423-33. [PubMed] [Google Scholar]

Tait SW, Green DR. Mitochondria and cell death: membrane permeabilization and beyond. Nat Rev Mol Cell Biol. 2010;11(9):621-32. [PubMed] [Google Scholar]

Mollazadeh H, Afshari AR, Hosseinzadeh H. Review on the potential therapeutic roles of Nigella sativa in the treatment of patients with cancer: involvement of apoptosis: black cumin and cancer. J Pharmacopuncture. 2017;20(3):158-72. [PubMed] [Google Scholar]

Rajesh S, Sivakumari K, Ashok K. In Silico docking of selected compound from Cardiospermum halicacabum Linn. leaf against human hepatocellular carcinoma (HepG-2) cell line. Int J Comput Bioinform In Silico Model. 2016;5(2):80-6. [Google Scholar]

Flora Priyadarshini J, Sivakumari K, Ashok K, Jayaprakash P, Rajesh S. GC-MS analysis for identification of active compounds in propolis and molecular docking studies of selected compounds against apoptotic proteins (Caspase-3, Caspase-9 and Β-Actin). J Biol Chem Res. 2018;35(2):349-58.

Jayameena P, Sivakumari K, Ashok K, Rajesh S. In silico molecular docking studies of rutin compound against apoptotic proteins (tumor necrosis factor, caspase-3, NF-kappa-B, p53, collagenase, nitric oxide synthase and cytochrome C). J Cancer Res Treat. 2018;6(2):28-33.

Jayaprakash P, Sivakumari K, Ashok K, Rajesh S. In silico molecular docking of alginic acid and fucoidan compound present in S. wightii against apoptotic proteins (caspase-3, caspase-9 and β -actin). Int J Biol Pharm Allied Sci. 2018;7(8):1551-65.

Karthika S, Sivakumari K, Rajesh S, Ashok K, Shyamala Devi K. In silico molecular prediction of ascorbic acid, betalain and gallic acid from Hylocereus undatus against apoptotic proteins (caspase-3, caspase-9 and β -actin). J Pharm Sci Innov. 2018;7(6):215-20.

Selvaraj R, Sivakumari K, Rajesh S, Ashok K. Molecular docking interaction of propolis with caspase-3, caspase-9, bax, bcl-2 and bcl-xl. Int J Res Analyt Rev. 2019;6(2):33-8. [Google Scholar]

Mohamad Sitheek A, Sivakumari K, Rajesh S, Ashok K. Molecular docking studies of apoptotic proteins caspase-3, caspase-9, bax, bcl-2 and bcl-xl with ethyl(2s)-2-methyl butanoate and 1-(ethylsulfanyl) ethane-1-thiol from durian fruit. Int J Biol Pharm Allied Sci. 2020;9(9):2513-23.

Ashok K, Sivakumari K, Sultana M, Rajesh S. In silico molecular docking and ADME potential of kiwi fruit isolated compounds against apoptotic proteins. Int J Biol Pharm Allied Sci. 2021;10(10):3607-19.

Manimekalai I, Sivakumari K, Rajesh S, Ashok K. Molecular docking studies of three mangostin compounds from Garcinia mangostana fruit with apoptotic proteins. Indian J Nat Sci. 2021;11(64):29446-51. [Google Scholar]

Oyinloye BE, Adekiya TA, Aruleba RT, Ojo OA, Ajiboye BO. Structure-based docking studies of GLUT4 towards exploring selected phytochemicals from Solanum xanthocarpum as a therapeutic target for the treatment of cancer. Curr Drug Discov Technol. 2019;16(4):406-16. [PubMed] [Google Scholar]

Hemalatha G, Sivakumari K, Rajesh S, Shyamala Devi K. In silico molecular docking stuides of Muricin J, Muricin K and Muricin L compound from A. muricata against apoptotic proteins (caspase-3, caspase-9 and β-actin). Inn Int J Sci. 2020;7(5):1-4. [Google Scholar]

Sander T. OSIRIS Property Explorer [Internet]. Organic Chemistry Portal; 2001 [cited 2022 Apr 19]. Available from: https://www.organic-chemistry.org/prog/peo/

Lipinski CA. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol. 2004;1(4):337-41. [PubMed] [Google Scholar]

Pollastri MP. Overview on the rule of five. Curr Protoc Pharmacol. 2010;49:1-8. [PubMed] [Google Scholar]

Richon AB. An introduction to molecular modelling. Mathematech. 1994;1:83.