Research Article

Cytotoxicity and Apoptosis Inducing Effects of Some Lathyrane and Tigliane Diterpenes against Breast Cancer Cell Lines

Abstract

Natural compounds and especially herbal medicine are of great interest due to their various biological effects and their potential to act as a drug for the treatment of various neoplasms especially breast cancer that we are facing with its increasing prevalence around the world. The aim of this study was to evaluate the cytotoxic and cell death mechanism of some diterpenoids (Lathyrane or Tigliane) extracted from the Euphorbia sogdiana Popov against two breast cancer cell lines, MCF-7 and 4T1. Determination the cytotoxic effects of four various diterpenoids was performed using MTT assay against MCF-7, 4T1, and HUVEC cell lines. The IC50 of each compound against cell lines was determined by drawing the dose-response graph using graph Pad prism software. Finally, the apoptotic effects of compound with the most cytotoxic effects was determined by flow cytometry assay for 24 hrs of incubation in IC50 concentration. Statistical analysis confirmed compound (3) with the most cytotoxicity against both cancer cell lines. The IC50 of compound (3) was determined as 10.1 ± 5, 28 ± 5, and 50 ± 3 µg/ml, for MCF-7, 4T1, and HUVEC cells, respectively. Furthermore, the cells treated with 5 and 10 μg/ml of compound (3) for 24 hrs, showed 49 and 57% of apoptosis. These surveyed compounds have the potential to be considered as useful anti-breast cancer agents due to the great cytotoxicity and apoptotic effects against related cancer cell lines and safety profile according to their rational selectivity index.

Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA: Cancer J Clin 2010;60:277-300.

Ghoncheh M, Pournamdar Z, Salehiniya H. Incidence and mortality and epidemiology of breast cancer in the world. Asian Pac J Cancer Prev 2016;17:43-46.

Yuan H, Ma Q, Ye L, Piao G. The traditional medicine and modern medicine from natural products. Molecules 2016;21:559.

Hong J. Role of natural product diversity in chemical biology. Curr Opin Chem Biol 2011;15:350-354.

Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat 2012;75:311-335.

Tholl D. Biosynthesis and biological functions of terpenoids in plants. In Biotechnology of isoprenoids. Springer. 2015; pp 63-106.

Jiao W, Dong W, Li Z, Deng M, Lu R. Lathyrane diterpenes from Euphorbia lathyris as modulators of multidrug resistance and their crystal structures. Bioorg Med Chem 2009;17:4786-4792.

Wang JX, Wang Q, Zhen YQ, Zhao SM, Gao F et al. Cytotoxic lathyrane-type diterpenes from seeds of Euphorbia lathyris. Chem Pharm Bull 2018:c17-00946.

Wang WP, Jiang K, Zhang P, Shen KK, Qu SJ et al. Highly oxygenated and structurally diverse diterpenoids from Euphorbia helioscopia. Phytochem 2018;145:93-102.

Ghanadian M, Ayatollahi AM, Mesaik MA, Afsharypuor S, Abdalla OM et al. New tigliane-type diterpenoids from Euphorbia aellenii Rech. f. with immunomodulatory activity. Res Pharm Sci 2011;6:35.

Chen H, Zhang R, Luo RH, Yang LM, Wang RR et al. Anti-HIV activities and mechanism of 12-O-tricosanoylphorbol-20-acetate, a novel phorbol ester from Ostodes katharinae. Molecules 2017;22:1498.

Wang HB, Chu WJ, Wang Y, Ji P, Wang YB et al. Diterpenoids from the roots of Euphorbia fischeriana. J Asian Nat Prod Res 2010;12:1038-1043.

Fatope MO, Zeng L, Ohayaga JE, Shi G, McLaughlin JL. Selectively cytotoxic diterpenes from Euphorbia poisonii. J Med Chem 1996;39:1005-1008.

Yazdiniapour Z, Ghanadian M, Zolfaghari B, Lanzotti V. (17)-Epoxylathyrane diterpenes from Euphorbia sogdiana Popov with cytotoxic activity. Fitoterapia 2016;108:87-92.

Ayatollahi AM, Ghanadian M, Afsharypuor S, Choudhary MI, Kobarfard F et al. Two new lathyrane type diterpenoids from Euphorbia aellenii. Fitoterapia 2010;81:891-893.

Betancur-Galvis L, Palomares E, Marco JA, Estornell E. Tigliane diterpenes from the latex of Euphorbia obtusifolia with inhibitory activity on the mammalian mitochondrial respiratory chain. J Ethnopharmacol 2003;85:279-282.

Shekofteh N, Boroujerdnia MG, Khosravi N, Kalantar K, Malek-Hosseini S et al. Apoptosis-inducing Effect of the Hexane Extracts from Three Native Iranian Euphorbia Plants. Int J Can Man 2017;10.

Wang JH, Zhou YJ, Bai X, He P. Jolkinolide B from Euphorbia fischeriana Steud induces apoptosis in human leukemic U937 cells through PI3K/Akt and XIAP pathways. Molecules 2011;32:451-457.

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IssueVol 6, No 2, 2021 QRcode
SectionResearch Article(s)
DOI https://doi.org/10.18502/tim.v6i2.6783
Keywords
Euphorbia sogdiana Popov Lathyrane Tigliane

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Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Maleki M, Yazdiniapour Z, Ghanadian M, Zolfaghari B, Rabbani F, Shafiee F. Cytotoxicity and Apoptosis Inducing Effects of Some Lathyrane and Tigliane Diterpenes against Breast Cancer Cell Lines. Trad Integr Med. 2021;6(2):103-110.