Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Investigating the Effects of Dorema hyrcanum Root Extracts on Selective Induction of Programmed Cell Death in Glioblastoma, Ovarian Cancer and Breast Cancer Cell Lines

Author(s): Mahsa Hatami Shandi, Shamim Sahranavard*, Fereshteh Bagheri, Zahra Shahsavari and Siamak Salami

Volume 24, Issue 10, 2024

Published on: 12 March, 2024

Page: [789 - 797] Pages: 9

DOI: 10.2174/0118715206273478240304095159

Price: $65

Abstract

Background: Despite remarkable advances, cancer has remained the second cause of death, which shows that more potent novel compounds should be found. Ethnobotanical compounds have a long history of treating diseases, and several approved chemotherapeutic compounds were isolated from plants.

Objective: The research aimed to evaluate the cytotoxic effects of Dorema hyrcanum root extract on ovarian, breast, and glioblastoma cells while examining its selectivity towards normal cells. Additionally, the study is directed to investigate cell death mechanisms, delineate modes of cell death, and explore intracellular ROS production.

Methods: Cytotoxic effects of alcoholic, dichloromethane, and petroleum ether fractions of Dorema hyrcanum were investigated on cancer and normal cells by using MTT assay, and the concentration around IC50 values was used for flow cytometric assessment of apoptosis, evaluation of the expression of selected genes via RT-qPCR and production of ROS.

Results: Methanolic extract exhibited the highest cytotoxicity, impacting A2780CP and MDA-MB-231. All fractions showed comparable effects on U251 cells. Notably, extracts displayed higher IC50 values in normal HDF cells, indicating cancer cell specificity. Flow cytometry revealed induction of apoptosis and non-apoptotic death in all three cancer cell lines. QPCR results showed upregulation of related genes, with RIP3K prominently increased in U251 glioblastoma. The DCFH-DA assay demonstrated ROS induction by the PE fraction exclusively in A2780CP cells after 30 minutes and up to 24 hours.

Conclusion: Dorema hyrcanum root extracts exhibited potent anti-tumor effects against all studied cell lines. The methanolic extract demonstrated the highest cytotoxicity, particularly against A2780CP and MDA-MB-231 cells. Importantly, all fractions displayed selectivity for cancer cells over normal HDF cells. Unique modes of action were observed, with the petroleum ether fraction inducing significant non-apoptotic cell death. These findings suggest promising therapeutic potential for Dorema hyrcanum in cancer treatment with subject to further mechanistic studies.

« Previous Next »
Graphical Abstract

[1]
Devlin, E.J.; Denson, L.A.; Whitford, H.S. Cancer treatment side effects: A meta-analysis of the relationship between response expectancies and experience. J. Pain Symp. Manag., 2017, 54(2), 245-258.
[http://dx.doi.org/10.1016/j.jpainsymman.2017.03.017]
[2]
Kroschinsky, F.; Stölzel, F.; von Bonin, S.; Beutel, G.; Kochanek, M.; Kiehl, M.; Schellongowski, P. New drugs, new toxicities: Severe side effects of modern targeted and immunotherapy of cancer and their management. Crit. Care, 2017, 21(1), 89.
[http://dx.doi.org/10.1186/s13054-017-1678-1] [PMID: 28407743]
[3]
Herrmann, J. Adverse cardiac effects of cancer therapies: Cardiotoxicity and arrhythmia. Nat. Rev. Cardiol., 2020, 17(8), 474-502.
[http://dx.doi.org/10.1038/s41569-020-0348-1] [PMID: 32231332]
[4]
Seitz, H.K.; Pöschl, G.; Simanowski, U.A. Alcohol and cancer. Recent Dev. Alcohol., 1998, 14, 67-95.
[PMID: 9751943]
[5]
Roy, P.S.; Saikia, B.J. Cancer and cure: A critical analysis. Indian J. Cancer, 2016, 53(3), 441-442.
[http://dx.doi.org/10.4103/0019-509X.200658] [PMID: 28244479]
[6]
Safarzadeh, E.; Sandoghchian Shotorbani, S.; Baradaran, B. Herbal medicine as inducers of apoptosis in cancer treatment. Adv. Pharm. Bull., 2014, 4(1), 421-427.
[PMID: 25364657]
[7]
Soltanian, S. The effect of plant-derived compounds in targeting cancer stem cells. J. Qazvin Uni. Med. Sci., 2019, 23(2), 164-181.
[http://dx.doi.org/10.32598/JQUMS.23.2.164]
[8]
Abdulridha, M.K.; Al-Marzoqi, A.H.; Al-awsi, G.R.L.; Mubarak, S.M.H.; Heidarifard, M.; Ghasemian, A. Anticancer effects of herbal medicine compounds and novel formulations: A literature review. J. Gastrointest. Cancer, 2020, 51(3), 765-773.
[http://dx.doi.org/10.1007/s12029-020-00385-0] [PMID: 32140897]
[9]
Koren, E.; Fuchs, Y. Modes of regulated cell death in cancer. Cancer Discov., 2021, 11(2), 245-265.
[http://dx.doi.org/10.1158/2159-8290.CD-20-0789] [PMID: 33462123]
[10]
Yan, G.; Elbadawi, M.; Efferth, T. Multiple cell death modalities and their key features (Review). World Acad. Sci. J., 2020, 2(2), 39-48.
[http://dx.doi.org/10.3892/wasj.2020.40]
[11]
Mottaghipisheh, J.; Vitalini, S.; Pezzani, R.; Iriti, M. A comprehensive review on ethnobotanical, phytochemical and pharmacological aspects of the genus Dorema. Phytochem. Rev., 2021, 20(5), 945-989.
[http://dx.doi.org/10.1007/s11101-020-09727-z]
[12]
Amiri, M.S.; Joharchi, M.R. Ethnobotanical knowledge of Apiaceae family in Iran: A review. Avicenna J. Phytomed., 2016, 6(6), 621-635.
[PMID: 28078243]
[13]
Zibaee, E.; Amiri, M.S.; Boghrati, Z.; Farhadi, F.; Ramezani, M.; Emami, S.A.; Sahebkar, A. Ethnomedicinal uses, phytochemistry and pharmacology of Dorema species (Apiaceae): A review. J. Pharmacopuncture, 2020, 23(3), 91-123.
[http://dx.doi.org/10.3831/KPI.2020.23.3.91] [PMID: 33072410]
[14]
Zugazagoitia, J.; Guedes, C.; Ponce, S.; Ferrer, I.; Molina-Pinelo, S.; Paz-Ares, L. Current challenges in cancer treatment. Clin. Ther., 2016, 38(7), 1551-1566.
[http://dx.doi.org/10.1016/j.clinthera.2016.03.026] [PMID: 27158009]
[15]
Wirsching, H.G.; Galanis, E.; Weller, M. Glioblastoma. Handb. Clin. Neurol., 2016, 134, 381-397.
[http://dx.doi.org/10.1016/B978-0-12-802997-8.00023-2] [PMID: 26948367]
[16]
Keyvani, V.; Farshchian, M.; Esmaeili, S.A.; Yari, H.; Moghbeli, M.; Nezhad, S.R.K.; Abbaszadegan, M.R. Ovarian cancer stem cells and targeted therapy. J. Ovarian Res., 2019, 12(1), 120.
[http://dx.doi.org/10.1186/s13048-019-0588-z] [PMID: 31810474]
[17]
Naghibi, F.; Ghafari, S.; Esmaeili, S.; Jenett-Siems, K. Naghibione; A novel sesquiterpenoid with antiplasmodial effect from Dorema hyrcanum koso-pol. Root, a plant used in traditional medicine. Iran. J. Pharm. Res., 2015, 14(3), 961-968.
[PMID: 26330887]
[18]
Chakraborty, S.; Rahman, T. The difficulties in cancer treatment. Ecancermedicalscience, 2012, 6, ed16.
[PMID: 24883085]
[19]
The global challenge of cancer. Nat. Can., 2020, 1(1), 1-2.
[http://dx.doi.org/10.1038/s43018-019-0023-9] [PMID: 35121840]
[20]
Delnavazi, M. Antioxidant and antibacterial activities of the essential oils and extracts of Dorema ammoniacum roots and aerial parts. Res. J. Pharmacogn., 2014, 1(4), 11-18.
[21]
Bannazadeh, A.M.; Rashtchizadeh, N.; Nazemiyeh, H.; Abdolalizadeh, J.; Mohammadnejad, L.; Baradaran, B. Investigating apoptotic effects of methanolic extract of Dorema glabrum seed on WEHI-164 cells. ISRN Pharmacol., 2013, 2013, 1-9.
[http://dx.doi.org/10.1155/2013/949871] [PMID: 23956872]
[22]
Jafari, N.; Zargar, S.J.; Yassa, N.; Delnavazi, M.R. Induction of apoptosis and cell cycle arrest by dorema glabrum root extracts in a gastric adenocarcinoma (AGS) cell line. Asian Pac. J. Cancer Prev., 2016, 17(12), 5189-5193.
[PMID: 28124886]
[23]
Mohammadi Pour, P.; Bidad, S.; Bahrami, G.; Hosseinzadeh, L.; Mojarrab, M.; Farzaei, M.H. Evaluation of the cytotoxicity of aqueous extract and oleo-essential oil of Dorema ammoniacum plant oleo-gum resin in some human cancer cell lines. Anal. Cell. Pathol., 2022, 2022, 1-9.
[http://dx.doi.org/10.1155/2022/9725244] [PMID: 35983460]
[24]
Abais, J.M.; Xia, M.; Zhang, Y.; Boini, K.M.; Li, P.L. Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector? Antioxid. Redox Signal., 2015, 22(13), 1111-1129.
[http://dx.doi.org/10.1089/ars.2014.5994] [PMID: 25330206]
[25]
Chen, H.; Lin, H.; Xie, S.; Huang, B.; Qian, Y.; Chen, K.; Niu, Y.; Shen, H.M.; Cai, J.; Li, P.; Leng, J.; Yang, H.; Xia, D.; Wu, Y. Myricetin inhibits NLRP3 inflammasome activation via reduction of ROS-dependent ubiquitination of ASC and promotion of ROS-independent NLRP3 ubiquitination. Toxicol. Appl. Pharmacol., 2019, 365, 19-29.
[http://dx.doi.org/10.1016/j.taap.2018.12.019] [PMID: 30594691]
[26]
Mworia, J.K.; Kibiti, C.M.; Ngugi, M.P.; Ngeranwa, J.N. Antipyretic potential of dichloromethane leaf extract of Eucalyptus globulus (Labill) and Senna didymobotrya (Fresenius) in rats models. Heliyon, 2019, 5(12), e02924.
[http://dx.doi.org/10.1016/j.heliyon.2019.e02924] [PMID: 31853510]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy