Study of Biological Activity of the Genus Spatholobus against Breast Cancer in Silico

Dodi Iskandar, Nashi Widodo, Warsito, Masruri, Rollando

Abstract

The development of apoptotic agents from natural plants has potential as promising breast cancer treatment candidates. The study on the efficacy of plants of the genus Spatholobus on breast cancer is still very limited. This study aims to explain the molecular mechanism that underlies the biological activity of breast anticancer from plants of the genus Spatholobus by in silico analysis. The method used has involved four techniques. First, the thirty-three compounds from plants of the genus Spatholobus were analyzed using the PASS server to obtain information about compounds that have breast cancer biological activity above 75%. Second, the thirteen selected compounds were evaluated using the STITCH server to determine their interactions with various proteins involved in apoptotic pathways and p53 signaling. Third, the thirteen breast anticancer compounds were re-selected to get pharmacological properties for safe consumption with the SwissADME server. Lastly, the selected nine compounds were further docked with target protein caspase-3 using the PyRx 0.99 tool and visualized with PyMol 2.5.2 and BIOVIA Discovery Studio Visualizer 2.1.1.0.2098. In conclusion, the nine compounds (lupinalbin A, trigraecum, coumestrol, maackiain, medioresinol, isoliquiritigenin, 8-O-methylretusin, biochanin A, and medicarpin) from the genus Spatholobus are predicted to have potential as activating agents for the caspase-3 protein and can suppress the growth of breast cancer cells.

 

Keywords: anticancer, bioactive compound, genus Spatholobus, apoptotic.

 

https://doi.org/10.55463/issn.1674-2974.49.2.19

 


Full Text:

PDF


References


WHO. THE GLOBAL CANCER OBSERVATORY. Cancer Incident in Indonesia. International Agency for Research on Cancer, 2020. [Online]. Available from: https://gco.iarc.fr/.

PISTRITTO G., TRISCIUOGLIO D., CECI C., GARUFI A., and D’ORAZI G. Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging, 2016, 8(4): 603-619, DOI: 10.18632/aging.100934.

ARAYA L.E., SONI I.V., HARDY J.A., and JULIEN O. Deorphanizing Caspase-3 and Caspase-9 Substrates In and Out of Apoptosis with Deep Substrate Profiling. ACS Chemical Biology, 2021, 16(11): 2280-2296. DOI: 10.1021/acschembio.1c00456.

AN H., HEO J.S., OOSHIMA A., WU Z., KIM S.-J., BAE I., and YANG K.-M. Abstract 989: Tetraarsenic hexoxide enhances generation of mitochondrial ROS to promote pyroptosis by inducing the activation of caspase-3/GSDME in triple-negative breast cancer cells. In: Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA, 2021. DOI: 10.1158/1538-7445.AM2021-989.

ESKANDARI E., EAVES C.J., and TAN S. Abstract 1949: Caspase-3 plays a requisite role in regulating survival of human breast cancer cells. In: Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA, 2021. DOI: 10.1158/1538-7445.AM2021-1949.

CHEN L., ZENG Y., and ZHOU S.-F. Role of Apoptosis in Cancer Resistance to Chemotherapy. In: TUTAR Y. (ed.) Current Understanding of Apoptosis, 2018. DOI: 10.5772/intechopen.80056.

THAPA S., RATHER R.A., SINGH S.K., and BHAGAT M. Insights into the Role of Defective Apoptosis in Cancer Pathogenesis and Therapy. In: TUTAR Y. (ed.) Regulation and Dysfunction of Apoptosis [Working Title], IntechOpen, 2021. DOI: 10.5772/intechopen.97536

CHEN F., ZHONG Z., TAN H.Y., WANG N., and FENG Y. The Underlying Mechanisms of Chinese Herbal Medicine-Induced Apoptotic Cell Death in Human Cancer. In: GALI-MUHTASIB H., and RAHAL O.N. (eds.) Programmed Cell Death, 2020.

CRAGG G.M., and PEZZUTO J.M. Natural Products as a Vital Source for the Discovery of Cancer Chemotherapeutic and Chemopreventive Agents. Medical Principles and Practice, 2016, 25(2): 41-59. DOI: 10.1159/000443404.

YANAGIHARA K., ITO A., TOGE T., and NUMOTO M. Antiproliferative Effects of Isoflavones on Human Cancer Cell Lines Established from the Gastrointestinal Tract. Cancer Research, 1993, 53(23): 5815-5821.

EMAMI S., and GHANBARIMASIR Z. Recent advances of chroman-4-one derivatives: Synthetic approaches and bioactivities. European Journal of Medicinal Chemistry, 2015, 93: 539-563. DOI: 10.1016/j.ejmech.2015.02.048.

TAY K.-C., TAN L.T.-H., CHAN C.K., HONG S.L., CHAN K.-G., YAP W.H., PUSPARAJAH P., LEE L.-H., and GOH B.-H. Formononetin: A Review of Its Anticancer Potentials and Mechanisms. Frontiers in Pharmacology, 2019, 10: 820. DOI: 10.3389/fphar.2019.00820.

THE PLANT LIST. Species in Spatholobus. [Online]. Available from: http://www.theplantlist.org/1.1/browse/A/Leguminosae/Spatholobus/.

CHRISTINA Y.I., NAFISAH W., ATHO'ILLAH M.F., RIFA'I M., WIDODO N., and DJATI M.S. Anti-breast cancer potential activity of Phaleria macrocarpa (Scheff.) Boerl. leaf extract through in silico studies. Journal of Pharmacy and Pharmacognosy Research, 2021, 9(6): 824-845.

LAGUNIN A.A., DUBOVSKAJA V.I., RUDIK A.V., POGODIN P.V., DRUZHILOVSKIY D.S., GLORIOZOVA T.A., FILIMONOV D.A., SASTRY N.G., and POROIKOV V.V. CLC-Pred: A freely available web-service for in silico prediction of human cell line cytotoxicity for drug-like compounds. PLOS ONE, 2018, 13(1): e0191838. DOI: 10.1371/journal.pone.0191838.

DAINA A., MICHIELIN O., and ZOETE V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 2017, 7(10): 1-13. DOI: 10.1038/srep42717.

YOON J.S., SUNG S.H., PARK J.H., and KIM Y.C. Flavonoids fromSpatholobus suberectus. Archives of Pharmacal Research, 2004, 27(6): 589-592. DOI: 10.1007/BF02980154.

YIN T., LIU H., WANG B., TU G.-Z., LIANG H., and ZHAO Y.-Y. Chemical constituents from Spatholobus sinensis. Acta Pharmaceutica Sinica, 2008, 43(1): 67-70. http://www.ncbi.nlm.nih.gov/pubmed/18357735.

SICHAEM J., RUKSILP T., SAWASDEE P., KHUMKRATOK S., and TIPPYANG S. Chemical Constituents of the Stems of Spatholobus parviflorus and Their Cholinesterase Inhibitory Activity. Chemistry of Natural Compounds, 2018, 54(2): 356-357. DOI: 10.1007/s10600-018-2344-9.

TANG R.-N., QU X.-B., GUAN S.-H., XU P.-P., SHI Y.-Y., and GUO D.-A. Chemical constituents of Spatholobus suberectus. Chinese Journal of Natural Medicines, 2012, 10(1): 32-35. DOI: 10.1016/S1875-5364(12)60007-7.

CUI Y., LIU P., and CHEN R. Studies on the chemical constituents of Spatholobus suberectus Dunn. Acta Pharmaceutica Sinica, 2002, 37(10): 784-787. http://www.ncbi.nlm.nih.gov/pubmed/12567862.

MUTAZAH R., HAMID H.A., RAMLI A.N.M., ALUWI F.M., and YUSOFF M.M. In vitro cytotoxicity of Clinacanthus nutans fractions on breast cancer cells and molecular docking study of sulfur-containing compounds against caspase-3, Food and Chemical Toxicology, 2020, 135: 110869. DOI: 10.1016/j.fct.2019.110869.

FIROOZPOUR L., GAO L., MOGHIMI S., PASALAR P., DAVOODI J., WANG M.-W., REZAEI Z., DADGAR A., YAHYAVI H., AMANLOU M., and FOROUMADI A. Efficient synthesis, biological evaluation, and docking study of isatin based derivatives as caspase inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, 2020, 35(1): 1674-1684. DOI: 10.1080/14756366.2020.1809388.

SIDDIQUI S., UPADHYAY S., AHMAD I., HUSSAIN A., and AHAMED M. Cytotoxicity of Moringa oleifera fruits on human liver cancer and molecular docking analysis of bioactive constituents against caspase‐3 enzyme. Journal of Food Biochemistry, 2021, 45(5). DOI: 10.1111/jfbc.13720.


Refbacks

  • There are currently no refbacks.