Gummosin, a sesquiterpene coumarin from Ferula assa-foetida is preferentially cytotoxic to human breast and prostate cancer cell lines

Document Type : Original Research Article


1 Department of Pharmacology and Toxicology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran.

2 AJA Cancer Epidemiology Research and Treatment Center (AJA- CERTC), AJA University of Medical Sciences, Tehran, Iran.

3 Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

4 Department of Pharmacology and Toxicology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran

5 Department of Physiology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran

6 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

7 Biochemistry Department, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran.


Objective: The present study was conducted to find cytotoxic compounds from oleo-gum-resin of Ferula assa-foetida (asafoetida).
Materials and Methods: A dichloromethane extract of asafoetida was subjected to different chromatography analyses (including column chromatography, preparative thin layer chromatography and high performance liquid chromatography) to isolate its bioactive sesquiterpene coumarins. The structures of isolated compounds were elucidated through 1H-NMR spectra interpretation and comparison with those reported in the literature. To measure the cytotoxic activity of pure compounds, a non-fluorescent substrate called resazurin (alamarBlue®)was used in this study. Human breast and prostate cancer cell lines (MCF-7 and PC-3, respectively) and a normal human embryonic stem cell (NIH) were treated with different concentrations (50, 25, 12.5 and 6.25 µg/mL) of pure compounds.
Results: In this study, 10 sesquiterpene coumarins were isolated from oleo-gum-resin of F. assa-foetida and cytotoxic activity of 6 compounds was tested against MCF-7 and PC-3 cell lines and NIH cells. Badrakemin acetate (7), ferukrinone (8) and deacetyl kellerin (10) were found for the first time in the oleo-gum-resin of F. assa-foetida. Gummosin (4) showed moderate cytotoxic activity with IC50 values of 30 and 32.1 µg/mL against PC-3 and MCF-7 cell lines, respectively. None of the isolated compounds showed toxicity against NIH as a normal human cell line.
Conclusion: The preferential cytotoxic activity of gummosin against cancer cell lines is reported for the first time in this study.


Main Subjects

Akaberi M, Iranshahy M, Iranshahi M. 2015. Review of the traditional uses, phytochemistry, pharmacology and toxicology of giant fennel (Ferula communis L. subsp. communis). Iran J Basic Med Sci, 18:1050-1062.
Alam M, Khan A, Wadood A, Khan A, Bashir S, Aman A, Jan AK, Rauf A, Ahmad B,Khan AR. 2016. Bioassay-guided isolation of sesquiterpene coumarins from Ferula narthex Bioss: a new anticancer agent. Front Pharmacol, 7:26-32.
Aldaghi L, Rad A, Arab A, Kasaian J, Iranshahi M, Sadr AS, Soltani F. 2016. In silico and in vitro evaluation of cytotoxic activities of farnesiferol c and microlobin on MCF-7, HeLa and KYSE cell lines. Drug Res (Stuttg), 66:532-538.
Alshammari S. 2016. Cytotoxic activity of ferula assa-foetida and Astragalus sarcocolla against cervical epithelial and colon carcinoma cell lines. ETD Collection for Tennessee State University. Paper AAI10119061.
Bagheri SM, Asl AA, Shams A, Mirghanizadeh-Bafghi SA, Hafizibarjin Z. 2017. Evaluation of cytotoxicity effects of Oleo-Gum-Resin and its essential oil of Ferula assa-foetida and ferulic acid on 4T1 breast cancer cells. Indian J Med Paediatr Oncol, 38:116-120.
Hasanzadeh D, Mahdavi M, Dehghan G, Charoudeh HN. 2017. Farnesiferol C induces cell cycle arrest and apoptosis mediated by oxidative stress in MCF-7 cell line. Toxicol Rep, 4:420-426.
Iranshahi M, Amin G, Shafiee A. 2004. A new coumarin from Ferula persica. Pharm Biol, 42:440-442.
Iranshahi M, Masullo M, Asili A, Hamedzadeh A, Jahanbin B, Festa M, Capasso A,Piacente S. 2010. Sesquiterpene coumarins from Ferula gumosa. J Nat Prod, 73:1958-1962.
Iranshahi M, Rezaee R, Najaf Najafi M, Haghbin A,Kasaian J. 2018. Cytotoxic activity of the genus Ferula (Apiaceae) and its bioactive constituents. Avicenna J Phytomed, 8:296-312.
Iranshahy M, Iranshahi M. 2011. Traditional uses, phytochemistry and pharmacology of asafoetida (Ferula assa-foetida oleo-gum-resin)-a review. J Ethnopharmacol, 134:1-10.
Kasaian J, Iranshahy M, Iranshahi M. 2014. Synthesis, biosynthesis and biological activities of galbanic acid - A review. Pharm Biol, 52:524-531.
Kasaian J, Mosaffa F, Behravan J, Masullo M, Piacente S, Ghandadi M, Iranshahi M. 2015. Reversal of P-glycoprotein-mediated multidrug resistance in MCF-7/Adr cancer cells by sesquiterpene coumarins. Fitoterapia, 103:149-154.
Kaur M, Kohli S, Sandhu S, Bansal Y, Bansal G. 2015. Coumarin: a promising scaffold for anticancer agents. Anticancer Agents Med Chem, 15:1032-1048.
Kim K-H, Lee H-J, Jeong S-J, Lee H-J, Lee E-O, Kim H-S, Zhang Y, Ryu S-Y, Lee M-H, Lü J. 2011. Galbanic acid isolated from Ferula assafoetida exerts in vivo anti-tumor activity in association with anti-angiogenesis and anti-proliferation. Pharm Res, 28:597-609.
Lee CL, Chiang LC, Cheng LH, Liaw CC, Abd El-Razek MH, Chang FR, Wu YC. 2009. Influenza A (H(1)N(1)) antiviral and cytotoxic agents from Ferula assa-foetida. J Nat Prod, 72:1568-1572.
Shafri M, Affendi M, Yusof FA, Zain M, Zulkarami A. 2015. In vitro cytotoxic activity of Ferula assafoetida on osteosarcoma cell line (HOS CRL). J Teknologi, 77:7-11.
Shakeri A, Iranshahy M, Iranshahi M. 2014. Biological properties and molecular targets of umbelliprenin--a mini-review. J Asian Nat Prod Res, 16:884-889.
Valiahdi S M, Iranshahi M, Sahebkar A. 2013. Cytotoxic activities of phytochemicals from Ferula species. DARU J Pharm Sci, 21:39-46.
van Haaften C, Duke CC, Weerheim AM, Smit NP, van Haard PM, Darroudi F, Trimbos BJ. 2011. Potent cytotoxic effects of Calomeria amaranthoides on ovarian cancers. J Exp Clin Cancer Res, 30:29-29.