Antiproliferative potential of Petiveria alliacea L extract-loaded nanodispersion against cancer cells
Ariadna Lafourcade Prada; Jesús Rafael Rodríguez Amado; Eduarda Tibúrcio do Nascimento Reis; Giovana Bicudo; Renata Trentin Perdomo; Marco António Utrera Martines
Abstract
Cancer is characterized by the uncontrolled growth of unhealthy cells that invade tissues and organs, causing thousands of deaths worldwide. In this work, a nanodispersion loaded with soft extract of Petiveria alliacea L. was developed for use as an antitumoral. The nanodispersion was prepared using the polymer deposition-solvent displacement method, with Kollicoat MAE 100P as the matrix former polymer. A nanodispersion with a particle size of 147 nm and high homogeneity of size (polydispersity index 0.162) was obtained, along with a ζ-potential of -10.80 mV. The polymer deposition-solvent displacement method allowed for high encapsulation efficiency (86.25%) and high stability on the shelf for a year. The nanodispersion did not show hemolytic effect and inhibited the growth of liver cancer cells (HepG2) with high selectivity (IG50 18.08 μg/mL, SI 13.82). The nanodispersion also showed strong antiproliferation activity and high selectivity against breast cancer cells (MDA-MB-231: IG50 28.22 μg/mL, SI 8.85) and kidney cancer cells (786-0: IG50 82.38 μg/mL, SI 3.03). Due to the low values of GI50 and selectivity higher than 3, the polymeric nanodispersion loaded with soft extract of Petiveria alliacea L. can be a promising product for the treatment of these three types of cancer. However, further studies will need to be conducted to investigate its actual usefulness in anticancer therapy.
Keywords
References
Abotaleb, M., Samuel, S. M., Varghese, E., Varghese, S., Kubatka, P., Liskova, A., & Büsselberg, D. (2018). Flavonoids in cancer and apoptosis. Cancers (Basel), 11(1), 28. PMid:30597838.
Agência Nacional de Vigilância Sanitária (2019). Farmacopeia Brasileira (5. ed., Vol. 1). ANVISA.
Ajji, P. K., Walder, K., & Puri, M. (2020). Combination of balsamin and flavonoids induce apoptotic effects in liver and breast cancer cells. Frontiers in Pharmacology, 11, 574496. http://dx.doi. org/10.3389/fphar.2020.574496. PMid:33192517.
Akintan, M. O., & Akinneye, J. O. (2020). Fumigant toxicity and phytochemical analysis of Petiveria alliacea (Linneaus) leaf and root bark oil on adult Culex quinquefasciatus. Bulletin of the National Research Center, 44(1), 129. http://dx.doi.org/10.1186/ s42269-020-00355-3.
Andrade, T. M., de Melo, A. S., Dias, R. G. C., Varela, E. L. P., de Oliveira, F. R., Vieira, J. L. F., de Andrade, M. A., Baetas, A. C., Monteiro, M. C., & Maia, C. D. S. F. (2012). Potential behavioral and pro-oxidant effects of Petiveria alliacea L. extract in adult rats. Journal of Ethnopharmacology, 143(2), 604-610. http://dx.doi.org/10.1016/j.jep.2012.07.020. PMid:22890225.
Awouafack, M. D., McGaw, L. J., Gottfried, S., Mbouangouere, R., Tane, P., Spiteller, M., & Eloff, J. N. (2013). Antimicrobial activity and cytotoxicity of the ethanol extract, fractions and eight compounds isolated from Eriosema robustum (Fabaceae). BMC Complementary and Alternative Medicine, 13(1), 289. http://dx.doi.org/10.1186/1472-6882-13-289. PMid:24165199.
Ayaz, M., Nawaz, A., Ahmad, S., Mosa, O. F., Eisa Hamdoon, A. A., Khalifa, M. A., Sadiq, A., Ullah, F., Wadood, A., Kabra, A., & Ananda Murthy, H. C. (2022). Underlying anticancer mechanisms and synergistic combinations of phytochemicals with cancer chemotherapeutics: Potential benefits and risks. Journal of Food Quality, 2022, 1-15. http://dx.doi.org/10.1155/2022/1189034.
BASF Pharm. (2019). Kollicoat Mae 100P: Technical information: Methacrylic acids/ethyl acrylates copolymer for enteric coating. BASF SE.
Batista, D. A., Betancourt, E., Zapata, E., Alfonso, A., Martínez, O., & Lemus, M. Z. (2011). Efecto protector de Petiveria alliacea L. (Anamú) sobre la inmunosupresión inducida por 5-fluoruracilo en ratones Balb/c. Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas, 10, 256-264.
Benevides, P. J. C., Young, M. C. M., Giesbrecht, A. M., Roque, N. F., & Bolzani, V. da S. (2001). Antifungal polysulphides from Petiveria alliacea L. Phytochemistry, 57(5), 743-747. http://dx.doi.org/10.1016/S0031-9422(01)00079-6. PMid:11397443.
British Pharmacopeia .(2019). British Pharmacopeia-BP 2019th ed., Vol. 1. Her Majesty Stationary Office. London-UK.
Cheong, J. N., Tan, C. P., Man, Y. B. C., & Misran, M. (2008). α-Tocopherol nanodispersions: Preparation, characterization and stability evaluation. Journal of Food Engineering, 89(2), 204-209. http://dx.doi.org/10.1016/j.jfoodeng.2008.04.018.
Cos, P., Vlietinck, A. J., Berghe, D., & Maes, L. (2006). Anti-infective potential of natural products: How to develop a stronger in vitro “proof-of-concept.”. Journal of Ethnopharmacology, 106(3), 290-302. PMid:16698208.
Duarte, M. R., & Lopes, J. F. (2005). Leaf and stem morphoanatomy of Petiveria alliacea. Fitoterapia, 76(7–8), 599-607. http://dx.doi. org/10.1016/j.fitote.2005.05.004. PMid:16242265.
Fessi, H., Puisieux, F., Devissaguet, J.P., Ammoury, N., Benita, S. (1989) Nanocapsule formation by interfacial polymer depositionfollowing solvent deplacement. Int. J. Pharm. 55, 25–28. http://dx.doi. org/10.1016/j.ijpharm.2004.05.016
Fibach, E., & Rachmilewitz, E. (2008). The role of oxidative stress in hemolytic anemia. Current Molecular Medicine, 8(7), 609-619. http://dx.doi.org/10.2174/156652408786241384. PMid:18991647.
Florentino Neto, S., Prada, A. L., Achod, L. D. R., Torquato, H. F. V., Lima, C. S., Paredes-Gamero, E. J., Silva de Moraes, M. O., Lima, E. S., Sosa, E. H., de Souza, T. P., & Amado, J. R. R. (2021). α-amyrin-loaded nanocapsules produce selective cytotoxic activity in leukemic cells. Biomedicine and Pharmacotherapy, 139, 111656. http://dx.doi.org/10.1016/j.biopha.2021.111656. PMid:34243603.
Food and Agriculture Organization. (2002). Human vitamins and mineral requirements. Report of a joint FAO/WHO expert consultation. FAO/WHO.
Germano, D. H. P., Caldeira, T. T. O., Mazella, A. A. G., Sertié, J. A. A., & Bacchi, E. M. (1993). Topical anti-inflammatory activity and toxicity of Petiveria alliacea. Fitoterapia, 64(5), 459-462.
Gomes, M. A., Priolli, D. G., Tralhão, J. G., & Botelho, M. F. (2013). Hepatocellular carcinoma: Epidemiology, biology, diagnosis, and therapies. Revista da Associação Médica Brasileira, 59(5), 514-524. PMid:24041910.
Grisson, S. M., & Berlin, J. A. (2013). Haemolytic activity and oxidative stress: Implications for redox-based therapies in sickle cell disease. Antioxidants & Redox Signaling, 18(7), 1255-1271.
Han, L. T., Fang, Y., Li, M. M., Yang, H. B., & Huang, F. (2013). The antitumor effects of triterpenoid saponins from the Anemone flaccida and the underlying mechanism. Evidence- Based Complementary and Alternative Medicine, 2013, 517931. http://dx.doi.org/10.1155/2013/517931. PMid:24191167.
Hernández, J. F., Urueña, C. P., Cifuentes, M. C., Sandoval, T. A., Pombo, L. M., Castañeda, D., Asea, A., & Fiorentino, S. (2014). A Petiveria alliacea standardized fraction induces breast adenocarcinoma cell death by modulating glycolytic metabolism. Journal of Ethnopharmacology, 153(3), 641-649. http://dx.doi. org/10.1016/j.jep.2014.03.013. PMid:24637191.
Hu, Z., Pan, J., Wang, J., Pei, Y., & Zhou, R. (2022). Current research status of alkaloids against breast cancer. The Chinese Journal of Physiology, 65(1), 12-20. http://dx.doi.org/10.4103/cjp. cjp_89_21. PMid:35229748.
Indrayanto, G., Putra, G. S., & Suhud, F. (2021). Validation of in-vitro bioassay methods: Application in herbal drug research. Profiles of Drug Substances, Excipients, and Related Methodology, 46, 273-307. http://dx.doi.org/10.1016/bs.podrm.2020.07.005. PMid:33461699.
Instituto Nacional de Câncer. (2022a). Atlas de mortalidade por câncer. INCA.
Instituto Nacional de Câncer. (2022b). Gastos federais atuais e futuros com os cânceres atribuíveis aos fatores de risco relacionados à alimentação, nutrição e atividade física no Brasil. INCA.
Iqbal, J., Abbasi, B. A., Mahmood, T., Kanwal, S., Ali, B., Shah, S. A., & Khalil, A. T. (2017). Plant-derived anticancer agents: A green anticancer approach. Asian Pacific Journal of Tropical Biomedicine, 7(12), 1129-1150. http://dx.doi.org/10.1016/j.apjtb.2017.10.016.
Kim, S., Kubec, R., & Musah, R. A. (2006). Antibacterial and antifungal activity of sulfur-containing compounds from Petiveria alliacea L. Journal of Ethnopharmacology, 104(1–2), 188-192. http://dx.doi. org/10.1016/j.jep.2005.08.072. PMid:16229980.
Klein, C., & Ladeira, E. A. (2004). Geochemistry and mineralogy of neoproterozoic banded iron-formations and some selected, siliceous manganese formations from the urucum district, Mato Grosso do Sul, Brazil. Economic Geology and the Bulletin of the Society of Economic Geologists, 99(6), 1233-1244. http://dx.doi. org/10.2113/gsecongeo.99.6.1233.
Kubec, R., & Musah, R. A. (2001). Cysteine sulfoxide derivatives in Petiveria alliacea. Phytochemistry, 58(6), 981-985. http:// dx.doi.org/10.1016/S0031-9422(01)00304-1. PMid:11684199.
Kubec, R., Kim, S., & Musah, R. A. (2002). S-Substituted cysteine derivatives and thiosulfinate formation in Petiveria alliacea: Part II. Phytochemistry, 61(6), 675-680. http://dx.doi.org/10.1016/ S0031-9422(02)00328-X. PMid:12423888.
Lima, T. C. M., Morato, G. S., & Takahashi, R. N. (1991). Evaluation of antinociceptive effect of Petiveria alliacea (Guine) in animals. Memorias do Instituto Oswaldo Cruz, 86(Suppl 2), 153-158. http://dx.doi.org/10.1590/S0074-02761991000600035. PMid:1841991.
Low, T., Rood, T., & Beresford, R. (1999). Segredos e virtudes das plantas medicinais (1st ed.). Reader`s Digest Brasil, Ltda. Marini, S., Jovicevic, L., Milanese, C., Giardina, B., Tentori, L., Leone, M. G., & Rossi, V. (1993). Effects of Petiveria Alliacea L. on cytokine production and natural killer cell activity. Pharmacological Research, 27, 107-108. http://dx.doi. org/10.1006/phrs.1993.1088.
Monks, A., Scudiero, D., Skehan, P., Shoemaker, R., Paull, K., Vistica, D., Hose, C., Langley, J., Cronise, P., Vaigro-Wolff, A., Gray-Goodrich, M., Campbell, H., Mayo, J., & Boyd, M. (1991). Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. JNCI Journal of the National Cancer Institute, 83(11), 757-766. http://dx.doi. org/10.1093/jnci/83.11.757. PMid:2041050.
National Institutes of Health. (2023). Cancer Stat Facts: Cancer of Any Site. NIH. https://seer.cancer.gov/statfacts/html/all.html
Olajubutu, O. G., Ogunremi, B. I., Adewole, A. H., Awotuya, O. I., Fakola, E. G., Anyim, G., & Faloye, K. O. (2022). Topical antiinflammatory activity of Petiveria alliacea, chemical profiling and computational investigation of phytoconstituents identified from its active fraction. Chemistry Africa, 5(3), 557-565. http://dx.doi. org/10.1007/s42250-022-00339-y.
Organisation for Economic Co-operation and Development. (2009). Preliminary review of OECD test guidelines for their applicability to manufactured nanomaterials. OECD.
Peña-Morán, O., Villarreal, M., Álvarez-Berber, L., Meneses-Acosta, A., & Rodríguez-López, V. (2016). Cytotoxicity, post-treatment recovery, and selectivity analysis of naturally occurring podophyllotoxins from Bursera fagaroides var. fagaroides on breast cancer cell lines. Molecules (Basel, Switzerland), 21(8), 1013. http://dx.doi.org/10.3390/molecules21081013. PMid:27527135.
Rodriguez Amado, J. R., Prada, A. L., Duarte, J. L., Keita, H., Silva, H. R., Ferreira, A. M., Sosa, E. H., & Carvalho, J. C. T. (2017). Development, stability, and in vitro delivery profile of new loratadine-loaded nanoparticles. Saudi Pharmaceutical Journal, 25(8), 1158-1168. http://dx.doi.org/10.1016/j.jsps.2017.07.008. PMid:30166904.
Rodriguez, A. J. R., Pérez, R. R., & Escalona, A. J. C. (2012). Standardization of the quality control parameters of the Tamarindus indica L. soft extract. Revista Cubana de Plantas Medicinales, 17(1), 108-114.
Roig, J. T. (1974). Plantas medicinales, aromáticas o venenosas de Cuba (3rd ed., Vol. 1). Instituto Cubano del Libro.
Samimi, S., Maghsoudnia, N., Eftekhari, R. B., & Dorkoosh, F. (2019). Lipid-based nanoparticles for drug delivery systems. In S. S. Mohapatra, S. Ranjan, N. Dasgupta, R. K. Mishra & S. Thomas (Eds.), Characterization and biology of nanomaterials for drug delivery (pp. 47-76). Elsevier. https://doi.org/10.1016/B978-0- 12-814031-4.00003-9
Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J. T., Bokesch, H., Kenney, S., & Boyd, M. R. (1990). New colorimetric cytotoxicity assay for anticancer-drug screening. JNCI Journal of the National Cancer Institute, 82(13), 1107-1112. http://dx.doi.org/10.1093/jnci/82.13.1107. PMid:2359136.
Sousa, J. R., Demuner, A. J., Pinheiro, J. A., Breitmaier, E., & Cassels, B. K. (1990). Dibenzyl trisulphide and trans-N-methyl-4- methoxyproline from Petiveria alliacea. Phytochemistry, 29(11), 3653-3655. http://dx.doi.org/10.1016/0031-9422(90)85294-P.
Taylor, L. (2002). Technical data report for anamú: Petiveria alliacea. Sage Press. https://www.rain-tree.com/reports/anamu-tech.pdf
United State Pharmacopeia. (2019). United States Pharmacopeial Convention (Vol. 1). Washington-USA.
Weerapreeyakul, N., Nonpunya, A., Barusrux, S., Thitimetharoch, T., & Sripanidkulchai, B. (2012). Evaluation of the anticancer potential of six herbs against a hepatoma cell line. Chinese Medicine, 7(1), 15. http://dx.doi.org/10.1186/1749-8546-7-15. PMid:22682026.
World Health Organization. (1998). Quality control methods for medicinal plant materials. WHO.
Submitted date:
06/17/2023
Accepted date:
11/03/2023