Saffron induces Apoptosis in Ovarian Cancer cell via MAPK and AKT/mTOR Pathways Saffron for ovarian cancer

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Ayse Guler Okyay
Halil Mahir Kaplan
Hasan Asil
Ergin Singirik


Saffrone, Ovarian cancer, MAPK, Apoptosis, AKT/mTOR


Study Objectives: Saffron and its main components have been shown to have anti-tumor and anticancer effects in animal studies and human cancer cell cultures. This study aimed to investigate the anti-cancer effects of saffron on human ovarian cancer cells. Methods: Powder of saffron was applied to the HO–8910 cell lines. Cell viability was determined. ELISA test is used to examine the activity of caspase-3 and expression of AIF, gadd153, grp78, caspase 3, bax, bcl-2, wee 1, which are apoptotic pathway’s mediators. Active ERK (p-ERK), active JNK (p-JNK) active AKT (p-AKT), and active mTOR (p-mTOR) were also analyzed by ELISA. Results: Saffron treatment reduced the viability of ovarian cancer cells. Saffron treatment increased activity of caspase 3 and expression of bax, wee 1, gadd153, grp78, and AIF and decreased bcl-2 which is anti-apoptotic protein. Saffron also decreased the activity of p-ERK, p-JNK, p-AKT, and p-mTOR in ovarian cancer cells. Conclusion: This study revealed that saffron has a beneficial effect on cancer treatment. Saffron may show a synergistic effect with various chemotherapeutics while directing the cancer cell to death. Crocetin, one of its active components, has shown a synergistic anti-cancer effect combined with cisplatin. Saffron induced apoptosis via ER stress, AKT/mTOR, and MAPK pathways in the ovarian cancer cell line.


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1. Samarghandian S., Borji A. Anticarcinogenic effect of saffron (Crocus sativus L.) and its ingredients. Pharmacognosy Research 2014; 6 (2): 99-107.
2. Kianbakht S, Mozaffari K. Effects of saffron and its Active Constituents, Crocin and Safranal, on Prevention of Indomethacin Induced Gastric Ulcers in Diabetic and Nondiabetic Rats. J Med Plants 2009;8:30‑8.
3. Hoshyar, R. and H. Mollaei, A comprehensive review on anticancer mechanisms of the main carotenoid of saffron, crocin. Journal of Pharmacy and Pharmacology, 2017. 69(11): p. 1419-1427.
4. Shafiee, M., et al., Saffron in the treatment of depression, anxiety and other mental disorders: Current evidence and potential mechanisms of action. Journal of Affective Disorders, 2018. 227: 330-337.
5. Khazdair, M.R., et al., The effects of Crocus sativus (saffron) and its constituents on nervous system: A review. Avicenna J Phytomed, 2015. 5(5): p. 376-91.
6. Abdullaev FI, Espinosa‑Aguirre JJ. Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect Prev 2004;28:426–32.
7. Yao, C., et al., Crocin induces autophagic apoptosis in hepatocellular carcinoma by inhibiting Akt/mTOR activity. Onco Targets Ther, 2018. 11: p. 2017-2028.
8. Asil, H., (2018). Safran’ın (Crocus sativus L.) Tıbbi ve Farmakolojik Özellikleri, 1. International Mersin Symposium, Conference Proceedings 2, 145-155.
9. Hoshyar, R., S.Z. Bathaie, and M. Sadeghizadeh, Crocin Triggers the Apoptosis through Increasing the Bax/Bcl-2 Ratio and Caspase Activation in Human Gastric Adenocarcinoma, AGS, Cells. DNA and Cell Biology, 2013. 32(2): p. 50-57.
10. Chen, S., et al., Crocin inhibits cell proliferation and enhances cisplatin and pemetrexed chemosensitivity in lung cancer cells. Transl Lung Cancer Res, 2015. 4(6): p. 775-83.
11. Samarghandian S, Borji A, Farahmand SK, Afshari R, Davoodi S. Crocus sativus L. (Saffron) Stigma Aqueous Extract Induces Apoptosis in Alveolar Human Lung Cancer Cells through Caspase-Dependent Pathways Activation. Biomed Res Int 2013; 2013:1-12.
12. Çıtak EÇ. 2000. "Apoptosis and cancer". Turkiye Klinikleri J Pediatr, 9(3),183-91.
13. Yazıcı P, Alizadehshargh S, Akdoğan GG. 2009." Apopitoz: Düzenleyici Moleküller, hastalıklarla İlişkisi ve Apopitozu Saptama Yöntemleri." Turkiye Klinikleri J Med Sci, 29(6),1677-86.
14. Call JA, Eckhardt SG, Camidge DR. "Targeted manipulation of apoptosis in cancer treatment. Lancet Oncol," 2008; 9(10):1002.
15. Heiser D, Labi V, Erlacher M, Villunger A. "The Bcl-2 protein family and its role in the development of neoplastic disease." ExpGerontol, 2004; 39(8): 1125-35.
16. Mousavi S.H., Tavakkol-Afshari J., Brook A., Jafari-Anarkooli I. Role of caspases and Bax protein in saffron-induced apoptosis in MCF-7 cells. Food and Chemical Toxicology 2009;47:1909-1913.
17. Berek, J.S., Natarajan S., Ovarian and Fallopian Tube Cancer, Berek& Novak's Gynecology, Lippincott William &Wilkins 2007. 14th edition, p1457-1548.
18. Kathawala R.J., Kudelka A., Rigas B. The Chemoprevention of Ovarian Cancer: the Need and the Options. Current Pharmacol Rep. 2018;4(3): 250-260. DOI: 10.1007/s40495-018-0133-6.
19. Hoshyar, R. and H. Mollaei, A comprehensive review on anticancer mechanisms of main carotenoid of saffron, crocin. Journal of Pharmacy and Pharmacology, 2017. 69(11): 1419-1427.
20. Moradzadeh, M., et al., Anti-tumor effects of crocetin and related molecular targets. Journal of Cellular Physiology, 2018. 233(3): p. 2170-2182.
21. Wang, W.A., J. Groenendyk, and M. Michalak, Endoplasmic reticulum stress associated responses in cancer. Biochimica Et Biophysica Acta-Molecular Cell Research, 2014. 1843(10): p. 2143-2149.
22. Dhillon, A.S., et al., MAP kinase signalling pathways in cancer. Oncogene, 2007. 26(22): p. 3279-3290.
23. Germann, U.A., et al., Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib). Molecular Cancer Therapeutics, 2017. 16(11): p. 2351-2363.
24. Aziz, A.U.R., et al., PIM Kinases and Their Relevance to the PI3K/AKT/mTOR Pathway in the Regulation of Ovarian Cancer. Biomolecules, 2018. 8(1).
25. Amin, A., et al., Saffron: A Potential Candidate for a Novel Anticancer Drug against Hepatocellular Carcinoma. Hepatology, 2011. 54(3): p. 857-867.