Persianolide-A, an Eudesmanolide-type Sesquiterpene Lactone from , Induces Apoptosis by Regulating ERK Signaling Pathways

Overview

Journal Res Pharm Sci

Specialty Chemistry

Date 2024 Jul 22

PMID 39035813

Authors

Seyyed Moein Ebrahimi

Jahanbakhsh Asadi

Maryam Fattahian

Seyyed Mehdi Jafari

Mustafa Ghanadian

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: Herbal components, particularly sesquiterpenes, are progressively recognized as a crucial resource for developing effective therapeutic agents for breast cancer. In this study, the effect of a sesquiterpene lactone known as 8-O-dihydroxy-11a,13-dihydroeudesma-4(15)-en-12,6a-olide (persianolide- A) was examined in breast cancer cell lines.

Experimental Approach: MDA-MB-231 and MCF-7 cancer cells were grown in DMEM solution with 10% FBS. Then, an MTT assay was performed to evaluate cell viability. Apoptosis was detected by annexin-PI staining. A caspase 3/7 activity assay kit was used to assess the activity of caspase-3 and caspase-7. Protein expression of Bcl-2, Bax, and p-ERK1/2 was determined by western blotting.

Findings/results: This study showed that the IC values of the persianolide-A for MCF-7 and MDA-MB- 468 cells are 34.76 and 54.48 μM, respectively. In addition, persianolide-A showed a significant increase in apoptosis in both MDAMB-231 and MCF-7 breast cancer cell lines. Persianolide-A significantly increased the expression of the pro-apoptotic protein Bax and decreased the expression of the anti-apoptotic protein Bcl-2. Also, presinolide-A treatment led to a substantial increase in caspase activity with a ratio of 3/7 in both MCF- 7 and MDA-MB-231 cancer cells. In addition, the study showed that persianolide-A decreased the expression of p-ERK1/2 protein.

Conclusion And Implications: The results of this study suggest that persianolide-A, sourced from induces cell apoptosis in breast cancer cell types. The molecular mechanisms could be implicated in the modulation of the ERK1/2 signaling pathway.

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References

Ghoncheh M, Pournamdar Z, Salehiniya H . Incidence and Mortality and Epidemiology of Breast Cancer in the World. Asian Pac J Cancer Prev. 2016; 17(S3):43-6. DOI: 10.7314/apjcp.2016.17.s3.43. View

Kohno M, Pouyssegur J . Targeting the ERK signaling pathway in cancer therapy. Ann Med. 2006; 38(3):200-11. DOI: 10.1080/07853890600551037. View

Paterson I, Anderson E . Chemistry. The renaissance of natural products as drug candidates. Science. 2005; 310(5747):451-3. DOI: 10.1126/science.1116364. View

Newman D, Cragg G . Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod. 2012; 75(3):311-35. PMC: 3721181. DOI: 10.1021/np200906s. View

Butler M . The role of natural product chemistry in drug discovery. J Nat Prod. 2004; 67(12):2141-53. DOI: 10.1021/np040106y. View

Shahali A, Ghanadian M, Jafari S, Aghaei M . Mitochondrial and caspase pathways are involved in the induction of apoptosis by nardosinen in MCF-7 breast cancer cell line. Res Pharm Sci. 2018; 13(1):12-21. PMC: 5772077. DOI: 10.4103/1735-5362.220963. View

Li Q, Chen M, Liu H, Yang L, Yang T, He G . The dual role of ERK signaling in the apoptosis of neurons. Front Biosci (Landmark Ed). 2014; 19(8):1411-7. DOI: 10.2741/4291. View

Wu T, Geng J, Guo W, Gao J, Zhu X . Asiatic acid inhibits lung cancer cell growth and by destroying mitochondria. Acta Pharm Sin B. 2017; 7(1):65-72. PMC: 5237705. DOI: 10.1016/j.apsb.2016.04.003. View

Chung T, Choi H, Lee J, Ha S, Kwak C, Abekura F . Oldenlandia diffusa suppresses metastatic potential through inhibiting matrix metalloproteinase-9 and intercellular adhesion molecule-1 expression via p38 and ERK1/2 MAPK pathways and induces apoptosis in human breast cancer MCF-7 cells. J Ethnopharmacol. 2016; 195:309-317. DOI: 10.1016/j.jep.2016.11.036. View

10.

Deshpande J, Choudhari A, Mishra M, Meghre V, Wadodkar S, Dorle A . Beneficial effects of Lagenaria siceraria (Mol.) Standley fruit epicarp in animal models. Indian J Exp Biol. 2008; 46(4):234-42. View

11.

Fattahian M, Ghanadian M, Zolfaghari B, Aghaei M, Zulfiqar F, Khan I . Phytochemical analysis of Artemisia kopetdaghensis: Sesquiterpene lactones with proapoptotic activity against prostate cancer cells. Phytochemistry. 2022; 203:113411. DOI: 10.1016/j.phytochem.2022.113411. View

12.

Chadwick M, Trewin H, Gawthrop F, Wagstaff C . Sesquiterpenoids lactones: benefits to plants and people. Int J Mol Sci. 2013; 14(6):12780-805. PMC: 3709812. DOI: 10.3390/ijms140612780. View

13.

Verma S, Rai V, Awasthee N, Dhasmana A, Rajalaksmi D, Nair M . Isodeoxyelephantopin, a Sesquiterpene Lactone Induces ROS Generation, Suppresses NF-κB Activation, Modulates LncRNA Expression and Exhibit Activities Against Breast Cancer. Sci Rep. 2019; 9(1):17980. PMC: 6884568. DOI: 10.1038/s41598-019-52971-3. View

14.

Kim H, Kim H, Lee E, Choi B, Jang H, Choi Y . A Quenched Annexin V-Fluorophore for the Real-Time Fluorescence Imaging of Apoptotic Processes In Vitro and In Vivo. Adv Sci (Weinh). 2020; 7(24):2002988. PMC: 7740095. DOI: 10.1002/advs.202002988. View

15.

Roy A, Manikkam R . Cytotoxic Impact of Costunolide Isolated from Costus speciosus on Breast Cancer via Differential Regulation of Cell Cycle-An In-vitro and In-silico Approach. Phytother Res. 2015; 29(10):1532-9. DOI: 10.1002/ptr.5408. View

16.

Siegel R, Miller K, Fuchs H, Jemal A . Cancer statistics, 2022. CA Cancer J Clin. 2022; 72(1):7-33. DOI: 10.3322/caac.21708. View

17.

Lee S, Cho Y, Lim J . Costunolide, a Sesquiterpene Lactone, Suppresses Skin Cancer via Induction of Apoptosis and Blockage of Cell Proliferation. Int J Mol Sci. 2021; 22(4). PMC: 7922093. DOI: 10.3390/ijms22042075. View

18.

Fallahian F, Aghaei M, Abdolmohammadi M, Hamzeloo-Moghadam M . Molecular mechanism of apoptosis induction by Gaillardin, a sesquiterpene lactone, in breast cancer cell lines : Gaillardin-induced apoptosis in breast cancer cell lines. Cell Biol Toxicol. 2016; 31(6):295-305. DOI: 10.1007/s10565-016-9312-6. View

19.

Ghantous A, Sinjab A, Herceg Z, Darwiche N . Parthenolide: from plant shoots to cancer roots. Drug Discov Today. 2013; 18(17-18):894-905. DOI: 10.1016/j.drudis.2013.05.005. View

20.

Quynh Doan N, Christensen S . Thapsigargin, Origin, Chemistry, Structure-Activity Relationships and Prodrug Development. Curr Pharm Des. 2015; 21(38):5501-17. DOI: 10.2174/1381612821666151002112824. View