IN VITRO AND IN SILICO APPROACH TO EVALUATE THE CYTOTOXICITY OF Carica papaya EXTRACTS AGAINST Saos-2 CELL LINE
DOI:
https://doi.org/10.55766/sujst10801Keywords:
Carica papaya, Anti-cancer analysis, OsteosarcomaAbstract
Osteosarcoma is the predominant form of bone cancer, which affects mostly adolescents and young adults. Despite therapeutic options, the prognosis for patients suffering with recurrent or advanced osteosarcoma remains poor. Carica papaya, a herbaceous plant, is well-known for its medicinal properties in traditional medicine. This study explores the therapeutic potential of Carica papaya leaf and seed extracts against osteosarcoma through an integrated in silico and in vitro approach. An MTT assay was performed to evaluate the apoptotic and cytotoxic effects against Saos-2 osteosarcoma cell line which demonstrated an IC50 value of 0.91% and 0.78% for leaf and seed extract respectively. In silico validation was carried out using network pharmacology to identify the top 10 hub genes. From molecular docking studies, we identified major bioactives such as flavones and androst-4-en-3-one,17-methoxy from leaf extract with good binding affinity to SRC, and 2-methyl-5H-dibenz[b,f]azepine and supraene from seed extract with ESR1, PARP1, AKT1, ERBB2. This study serves as a preliminary investigation into the anticancer property of Carica papaya against osteosarcoma and the results suggest its promise as a natural therapeutic agent for osteosarcoma.
References
Alotaibi, K. S., Li, H., Rafi, R., & Siddiqui, R. A. (2017). Papaya black seeds have beneficial anticancer effects on PC-3 prostate cancer cells. Journal of Cancer Metastasis and Treatment, 3(8), 161-168. https://doi.org/10.20517/2394-4722.2017.33
Aradhya, M. K., Manshardt, R. M., Zee, F., & Morden, C. W. (1999). A phylogenetic analysis of the genus Carica L. (Caricaceae) based on restriction fragment length variation in a cpDNA intergenic spacer region. Genetic Resources and Crop Evolution, 46(6), 579-586. https://doi.org/10.1023/A:1008786531609
Bland, R., Sammons, R. L., Sheppard, M. C., & Williams, G. R. (1997). Thyroid hormone, vitamin D and retinoid receptor expression and signalling in primary cultures of rat osteoblastic and immortalised osteosarcoma cells. Journal of Endocrinology, 154(1), 63-74. https://doi.org/10.1677/joe.0.1540063
Chen, Q., Zhou, Z., Shan, L., Zeng, H., Hua, Y., & Cai, Z. (2015). The importance of Src signaling in sarcoma. Oncology Letters, 10(1), 17-22. https://doi.org/10.3892/ol.2015.3184
Czarnecka, A. M., Synoradzki, K., Firlej, W., Bartnik, E., Sobczuk, P., Fiedorowicz, M., Grieb, P., & Rutkowski, P. (2020). Molecular biology of osteosarcoma. Cancers, 12(8), Article 2130. https://doi.org/10.3390/cancers12082130
Fauziya, S., & Krishnamurthy, R. (2013). Papaya (Carica papaya): Source material for anticancer. CIBTech Journal of Pharmaceutical Sciences, 2(1), 25–33.
Haber, R. A., Garcia, R. D., Hernandez, J. N., Jamieson, S., Mondal, A., & Bishayee, A. (2023). Papaya (Carica papaya L.) for cancer prevention: Progress and promise. Critical Reviews in Food Science and Nutrition, 63(30), 10499-10519. https://doi.org/10.1080/10408398.2022.2079607
Hamed, A. N., Abouelela, M. E., El Zowalaty, A. E., Badr, M. M., & Abdelkader, M. S. (2022). Chemical constituents from Carica papaya Linn. leaves as potential cytotoxic, EGFR wt and aromatase (CYP19A) inhibitors: A study supported by molecular docking. RSC Advances, 12(15), 9154-9162. https://doi.org/10.1039/D1RA07000B
Hinoi, E., Osumi, R., Sugihara, K., Yoshimoto, M., Tokumura, K., & Tanaka, Y. (2024). Role of proteoglycan synthesis genes in osteosarcoma stem cells. Frontiers in Oncology, 14, Article 1325794. https://doi.org/10.3389/fonc.2024.1325794
Hu, W., Wu, X., Tang, J., Zhao, G., Xiao, N., Zhang, L., & Li, S. (2019). Anti-cancer targets of formononetin and molecular mechanisms in osteosarcoma: Findings of bioinformatic and experimental assays. Journal of Cellular and Molecular Medicine, 23(5), 3505-3511. https://doi.org/10.1111/jcmm.14248
Imaga, N. A., Gbenle, G. O., Okochi, V. I., Adenekan, S., Duro-Emmanuel, T., Oyeniyi, B., Dokai, P. N., Oyenuga, M., Otumara, A., & Ekeh, F. C. (2010). Phytochemical and antioxidant nutrient constituents of Carica papaya and Parquetina nigrescens extracts. Scientific Research and Essays, 5(16), 2201-2205.
Iyappan, G., Daniel, D., & Poovanalingam, T. (2014). Ascertaining the phytocomponents in the crude ethanolic extracts of Carica papaya seeds by GC-MS. World Journal of Pharmacy and Pharmaceutical Sciences, 3(9), 942-949.
Kermanshai, R., McCarry, B. E., Rosenfeld, J., Summers, P. S., Weretilnyk, E. A., & Sorger, G. J. (2001). Benzyl isothiocyanate is the chief or sole anthelmintic in papaya seed extracts. Phytochemistry, 57(3), 427-435. https://doi.org/10.1016/S0031-9422(01)00077-2
Krishna, K. L., Paridhavi, M., & Patel, J. A. (2008). Review on nutritional, medicinal and pharmacological properties of papaya (Carica papaya Linn.). Natural Product Radiance, 7(4), 364-373.
Liu, Y., Ma, Y. H., Sun, Z. Z., Rui, Y. J., Yin, Q. D., Song, S., Wei, X. M., Liu, J., Liu, X. G., & Hu, K. J. (2014). Effect of c-erbB2 overexpression on prognosis in osteosarcoma: Evidence from eight studies. Tumor Biology, 35(9), 8939-8943. https://doi.org/10.1007/s13277-014-2165-9
Lolok, N., Sumiwi, S. A., Muhtadi, A., Susilawati, Y., Hendriani, R., Ramadhan, D. S. F., & Sahidin, I. (2022). Molecular docking and molecular dynamics studies of bioactive compounds contained in noni fruit (Morinda citrifolia L.) against human pancreatic α-amylase. Journal of Biomolecular Structure and Dynamics, 40(15), 7091-7098. https://doi.org/10.1080/07391102.2021.1894981
Mahrous, N. S., & Noseer, E. A. (2023). Anticancer potential of Carica papaya Linn black seed extract against human colon cancer cell line: In vitro study. BMC Complementary Medicine and Therapies, 23(1), Article 271. https://doi.org/10.1186/s12906-023-04085-7
Misaghi, A., Goldin, A., Awad, M., & Kulidjian, A. A. (2018). Osteosarcoma: A comprehensive review. SICOT-J, 4, Article 12. https://doi.org/10.1051/sicotj/2017028
Nguyen, T. T., Shaw, P. N., Parat, M. O., & Hewavitharana, A. K. (2013). Anticancer activity of Carica papaya: A review. Molecular Nutrition & Food Research, 57(1), 153-164. https://doi.org/10.1002/mnfr.201200388
Nikitovic, D., Berdiaki, K., Chalkiadaki, G., Karamanos, N., & Tzanakakis, G. (2008). The role of SLRP-proteoglycans in osteosarcoma pathogenesis. Connective Tissue Research, 49(3-4), 235-238. https://doi.org/10.1080/03008200802147589
Otsuki, N., Dang, N. H., Kumagai, E., Kondo, A., Iwata, S., & Morimoto, C. (2010). Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects. Journal of Ethnopharmacology, 127(3), 760-767. https://doi.org/10.1016/j.jep.2009.11.024
Papachristou, D. J., & Papavassiliou, A. G. (2007). Osteosarcoma and chondrosarcoma: New signaling pathways as targets for novel therapeutic interventions. The International Journal of Biochemistry & Cell Biology, 39(5), 857-862. https://doi.org/10.1016/j.biocel.2006.12.003
Raj, P. D., Reddy, P. R., Thiruvanavukkarasu, P., Rajesh, S., & Hari, R. (2022). Anticancer activity of phyto ligands from Carica papaya leaves by suppression of PI3CKA and BCL2 proteins: An in silico approach. Biomedical and Pharmacology Journal, 15(3), 1289-1298. https://doi.org/10.13005/bpj/2466
Rashed, K. N., & Fouche, G. (2013). Anticancer activity of Carica papaya extracts in vitro and phytochemical analysis. Greener Journal of Pharmacy and Pharmacology, 1(1), 1-5.
Rhim, J. S., Kim, C. M., Arnstein, P., Huebner, R. J., Weisburger, E. K., & Nelson-Rees, W. A. (1975). Transformation of human osteosarcoma cells by a chemical carcinogen. Journal of the National Cancer Institute, 55(6), 1291-1294. https://doi.org/10.1093/jnci/55.6.1291
Rifaath, M., Santhakumar, P., & Selvaraj, J. (2022). Effect of Carica papaya on beta catenin and Wnt mRNA expression in human colon cancer (HT-29) cells in vitro. Bioinformation, 18(3), 289-295. https://doi.org/10.6026/97320630018289
Shaikh, J. R., & Patil, M. (2020). Qualitative tests for preliminary phytochemical screening: An overview. International Journal of Chemical Studies, 8(2), 603-608.
Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A. E., & Berendsen, H. J. C. (2005). GROMACS: Fast, flexible, and free. Journal of Computational Chemistry, 26(16), 1701-1718. https://doi.org/10.1002/jcc.20291
Vij, T., & Prashar, Y. (2015). A review on medicinal properties of Carica papaya Linn. Asian Pacific Journal of Tropical Disease, 5(1), 1-6. https://doi.org/10.1016/S2222-1808(14)60617-4
Wang, T., Wang, D., Zhang, L., Yang, P., Wang, J., Liu, Q., Yan, F., & Lin, F. (2019). The TGFβ-miR-499a-SHKBP1 pathway induces resistance to EGFR inhibitors in osteosarcoma cancer stem cell-like cells. Journal of Experimental & Clinical Cancer Research, 38(1), Article 226. https://doi.org/10.1186/s13046-019-1195-y
Xin, S., & Wei, G. (2020). Prognostic factors in osteosarcoma: A study level meta-analysis and systematic review of current practice. Journal of Bone Oncology, 21, Article 100281. https://doi.org/10.1016/j.jbo.2020.100281
Zhang, J., Yu, X. H., Yan, Y. G., Wang, C., & Wang, W. J. (2015). PI3K/Akt signaling in osteosarcoma. Clinica Chimica Acta, 444, 182-192. https://doi.org/10.1016/j.cca.2014.12.041
Zhu, J., Liu, Y., Zhu, Y., Zeng, M., Xie, J., Lei, P., Li, K., & Hu, Y. (2017). Role of RANK and Akt1 activation in human osteosarcoma progression: A clinicopathological study. Experimental and Therapeutic Medicine, 13(6), 2862-2866. https://doi.org/10.3892/etm.2017.4360
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