Bioactive compounds identified in Ayapana triplinervis: A review of antitumor mechanisms

Authors

DOI:

https://doi.org/10.33448/rsd-v11i6.28478

Keywords:

Secondary metabolites; Tumorigenesis; Oxidative stress; Genotoxicity; Ayapana triplinveris.

Abstract

Cancer is one of the most important causes of death in the world. Mitochondrial dysfunctions – related to mutation or not –, oxidative stress and activation of immune cells are related to the pathophysiology of cancer, due to the induction of oncogenic factors by multiple pathways. Heretofore, the production and development of antitumor drugs for the treatment of cancer is still a barrier, until the formulation is available in safe conditions to patients. In this sense, the approach with plants of reported traditional use, such as Ayapana triplinervis, started to draw attention owing to the great observed potential of its secondary metabolites and the widespread use. Phytosterols and flavonoids are widely consumed as nutraceuticals and have reported antioxidant and anti-inflammatory actions. Thus, the present integrative review aimed to gather the mechanisms by which compounds previously identified in A. triplinervis perform antitumor activity, in addition, we sought to present toxicological aspects attributed to these molecules. Based on a critical analysis of the selected literature, the present review gathers data, which show that the metabolites β-sitosterol, stigmasterol and kaempferol play a significant antitumor role through mitochondrial dysfunction, oxidative pathways and modulation of genes. Regarding the toxicological aspects of these molecules, the present study emphasizes the importance of experimental designs in in vivo models, given the need to perform assertive calculations of effective doses – for antitumor activity – and toxic of these compounds.

References

Bae, H., Song, G., & Lim, W. (2020). Stigmasterol causes ovarian cancer cell apoptosis by inducing endoplasmic reticulum and mitochondrial dysfunction. Pharmaceutics, 12(6), 488.

Bugel, S. M., Bonventre, J. A., & Tanguay, R. L. (2016). Comparative Developmental Toxicity of Flavonoids Using an Integrative Zebrafish System. Toxicological sciences : an official journal of the Society of Toxicology, 154(1), 55–68. https://doi.org/10.1093/toxsci/kfw139

Castle, B. T., Mccubbin, S., Prahl, L. S., Bernens, J. N., Sept, D., & Odde, D. J. (2017). Mechanisms of kinetic stabilization by the drugs paclitaxel and vinblastine. Molecular biology of the cell, 28(9), 1238–1257. https://doi.org/10.1091/mbc.E16-08-0567

Dabravolski, S. A., Nikiforov, N. G., Zhuravlev, A. D., Orekhov, N. A., Mikhaleva, L. M., & Orekhov, A. N. (2022). The Role of Altered Mitochondrial Metabolism in Thyroid Cancer Development and Mitochondria-Targeted Thyroid Cancer Treatment. International Journal of Molecular Sciences, 23(1), 460.

Devi, K. P., Malar, D. S., Nabavi, S. F., Sureda, A., Xiao, J., Nabavi, S. M., & Daglia, M. (2015). Kaempferol and inflammation: From chemistry to medicine. Pharmacological research, 99, 1–10.

Dias, M. C., Pinto, D., & Silva, A. (2021). Plant Flavonoids: Chemical Characteristics and Biological Activity. Molecules (Basel, Switzerland), 26(17), 5377.

Dong, Y., Chen, C., Chen, C., Zhang, C., Zhang, L., Zhang, Y., ... & Dong, Z. (2021). Stigmasterol inhibits the progression of lung cancer by regulating retinoic acid-related orphan receptor C. Histology and histopathology, 18388.

Guo, H., Ren, F., Zhang, L., Zhang, X., Yang, R., Xie, B., Li, Z., Hu, Z., Duan, Z., & Zhang, J. (2016). Kaempferol induces apoptosis in HepG2 cells via activation of the endoplasmic reticulum stress pathway. Molecular medicine reports, 13(3), 2791–2800. https://doi.org/10.3892/mmr.2016.4845

Imran, M., Salehi, B., Sharifi-Rad, J., Aslam Gondal, T., Saeed, F., Imran, A., Shahbaz, M., Tsouh Fokou, P. V., Umair Arshad, M., Khan, H., Guerreiro, S. G., Martins, N., & Estevinho, L. M. (2019). Kaempferol: A Key Emphasis to Its Anticancer Potential. Molecules (Basel, Switzerland), 24(12), 2277.

Jie, F., Yang, X., Wu, L., Wang, M., & Lu, B. (2021). Linking phytosterols and oxyphytosterols from food to brain health: origins, effects, and underlying mechanisms. Critical reviews in food science and nutrition, 1–18.

Lei, X., Guo, J., Wang, Y., Cui, J., Feng, B., Su, Y., Zhao, H., Yang, W., & Hu, Y. (2019). Inhibition of endometrial carcinoma by Kaempferol is interceded through apoptosis induction, G2/M phase cell cycle arrest, suppression of cell invasion and upregulation of m-TOR/PI3K signalling pathway. Journal of B.U.ON. : official journal of the Balkan Union of Oncology, 24(4), 1555–1561.

Mahaddalkar, T., Suri, C., Naik, P. K., & Lopus, M. (2015). Biochemical characterization and molecular dynamic simulation of β-sitosterol as a tubulin-binding anticancer agent. European journal of pharmacology, 760, 154–162. https://doi.org/10.1016/j.ejphar.2015.04.014

Maleki, S. J., Crespo, J. F., & Cabanillas, B. (2019). Anti-inflammatory effects of flavonoids. Food chemistry, 299, 125124.

Martins, I. R., Onuki, J., Miyamoto, S., & Uemi, M. (2020). Characterization of oxyphytosterols generated by β-sitosterol ozonization. Archives of biochemistry and biophysics, 689, 108472.

Miyamoto, S., Lima, R. S., Inague, A., & Viviani, L. G. (2021). Electrophilic oxysterols: generation, measurement and protein modification. Free radical research, 55(4), 416–440.

Olsen J, Overvad K. (1993). The concept of multifactorial etiology of cancer. Pharmacology & toxicology, 72(1), 33-8.

Pereira, A. S., Shitsuka, D. M., Parreira, F. J., & Shitsuka, R. (2018). Metodologia da pesquisa científica.

Qureshy, Z., Johnson, D. E., & Grandis, J. R. (2020). Targeting the JAK/STAT pathway in solid tumors. Journal of cancer metastasis and treatment, 6, 27.

Rajavel, T., Mohankumar, R., Archunan, G., Ruckmani, K., & Devi, K. P. (2017). Beta sitosterol and Daucosterol (phytosterols identified in Grewia tiliaefolia) perturbs cell cycle and induces apoptotic cell death in A549 cells. Scientific reports, 7(1), 3418. https://doi.org/10.1038/s41598-017-03511-4

Ruiz De La Cruz, M., De La Cruz Montoya, A. H., Rojas Jiménez, E. A., Martínez Gregorio, H., Díaz Velásquez, C. E., Paredes De La Vega, J., ... & Vaca Paniagua, F. (2021). Cis-Acting Factors Causing Secondary Epimutations: Impact on the Risk for Cancer and Other Diseases. Cancers, 13(19), 4807.

Sharma, N., Biswas, S., Al-Dayan, N., Alhegaili, A. S., & Sarwat, M. (2021). Antioxidant Role of Kaempferol in Prevention of Hepatocellular Carcinoma. Antioxidants (Basel, Switzerland), 10(9), 1419.

Souza, M. T. de, Silva, M. D. da, & Carvalho, R. de. (2010). Integrative review: what is it? How to do it? Einstein (São Paulo), 8(1), 102–106. https://doi.org/10.1590/s1679-45082010rw1134

Synn, C. B., Kim, D. K., Kim, J. H., Byeon, Y., Kim, Y. S., Yun, M. R., ... & Pyo, K. H. (2022). Primary Tumor Suppression and Systemic Immune Activation of Macrophages through the Sting Pathway in Metastatic Skin Tumor. Yonsei medical journal, 63(1), 42.

Taïlé, J., Arcambal, A., Clerc, P., Gauvin-Bialecki, A., & Gonthier, M. P. (2020). Medicinal Plant Polyphenols Attenuate Oxidative Stress and Improve Inflammatory and Vasoactive Markers in Cerebral Endothelial Cells during Hyperglycemic Condition. Antioxidants (Basel, Switzerland), 9(7), 573. https://doi.org/10.3390/antiox9070573

Takayasu, B. S., Martins, I. R., Garnique, A., Miyamoto, S., Machado-Santelli, G. M., UEMI, M., & ONUKI, J. (2020). Biological effects of an oxyphytosterol generated by β-Sitosterol ozonization. Archives of biochemistry and biophysics, 696, 108654.

Viet Huong, D.T., Giang, P.M., & Trang, V.M. (2020). Coumarins and Polar Constituents from Eupatorium triplinerve and Evaluation of Their α-Glucosidase Inhibitory Activity. Journal of Chemistry, 2020, 1-8.

Wang, F., Wang, L., Qu, C., Chen, L., Geng, Y., Cheng, C., ... & Chen, Z. (2021). Kaempferol induces ROS-dependent apoptosis in pancreatic cancer cells via TGM2-mediated Akt/mTOR signaling. BMC cancer, 21(1), 1-11.

World Health Organization (2020). Global Health Estimates 2020: Deaths by Cause, Age, Sex, by Country and by Region, 2000-2019.

Zhao, H., Zhang, X., Wang, M., Lin, Y., & Zhou, S. (2021). Stigmasterol Simultaneously Induces Apoptosis and Protective Autophagy by Inhibiting Akt/mTOR Pathway in Gastric Cancer Cells. Frontiers in oncology, 11, 629008. https://doi.org/10.3389/fonc.2021.62900

Zhu, L., & Xue, L. (2019). Kaempferol Suppresses Proliferation and Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Breast Cancer Cells. Oncology research, 27(6), 629–634. https://doi.org/10.3727/096504018X15228018559434

Published

17/04/2022

How to Cite

ROMEIRO, C. F. R.; PANTOJA, L. V. P. da S.; ANDRADE, M. A. de. Bioactive compounds identified in Ayapana triplinervis: A review of antitumor mechanisms. Research, Society and Development, [S. l.], v. 11, n. 6, p. e0811628478, 2022. DOI: 10.33448/rsd-v11i6.28478. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/28478. Acesso em: 28 may. 2022.

Issue

Section

Health Sciences