Moraea sisyrinchium inhibits proliferation, cell cycle, and migration of cancerous cells, and decreases angiogenesis in chick chorioallantoic membrane

Document Type : Original Article

Authors

1 Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Biology, Payame Noor University, Tehran, Iran

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

10.22038/ijbms.2023.70554.15353

Abstract

Objective(s): Experimental studies reported that some plants in the genus of Moraea (Iridaceae family) show anticancer potential. This study aimed to evaluate the effects of Moraea sisyrinchium on U87 glioblastoma multiforme and HepG2 liver cancer cells.
Materials and Methods: The cells were incubated for 24 hr with hydroalcoholic extract of the stem, flower, and bulb of M. sisyrinchium. Then, the cell proliferation (MTT) assay, cell cycle analysis (propidium iodide staining), cell migration test (scratch), Western blotting (Bax and Bcl-2 expression), and gelatin zymography (for matrix metalloproteinases, MMPs) were performed. Oxidative stress was evaluated by determining the levels of reactive oxygen species and lipid peroxidation. Angiogenesis was evaluated on chick embryo chorioallantoic membrane.
Results: The extracts of the flower, stem, and bulb significantly decreased the proliferation of HepG2 and U87 cells. This effect was more for U87 than HepG2 and for the bulb and stem than the flower. In U87 cells, the bulb extract increased oxidative stress, cell cycle arrest, and the Bax/Bcl-2 ratio. Also, this extract suppressed the migration ability of HepG2 and U87 cells, which was associated with the inhibition of MMP2 activity. In addition, it significantly reduced the number and diameter of vessels in the chorioallantoic membrane. Liquid chromatography-mass spectrometry revealed the presence of xanthones (bellidifolin and mangiferin), flavonoids (quercetin and luteolin), isoflavones (iridin and tectorigenin), and phytosterols (e.g., stigmasterol) in the bulb.
Conclusion: M. sisyrinchium bulb decreased the proliferation and survival of cancer cells by inducing oxidative stress. It also reduced the migration ability of the cells and inhibited angiogenesis.

Keywords

Main Subjects


1. Hosseini A, Ghorbani A. Cancer therapy with phytochemicals: Evidence from clinical studies. Avicenna J Phytomed 2015; 5:84-97.
2. Buyel J. Plants as sources of natural and recombinant anti-cancer agents. Biotechnol Adv 2018; 36:506-520.
3. Ogar GO, Minari JB, Bello AJ, Chiwetalu J, Omogunwa OE, Oshikoya, OS, et al. Influence of ethanolic extract of Allium sativum on TP53 gene and its anticancer potential in NNitrosodiethylamine (NDEA)-induced hepatocellular carcinoma in male albino rats. Iran J Basic Med Sci 2022; 25:497-505.
4. Hooshmand S, Mahdinezhad MR, Taraz Jamshidi S, Soukhtanloo M, Mirzavi F, Iranshahi M, et al. Morus nigra L. extract prolongs survival of rats with hepatocellular carcinoma. Phytother Res 2021; 35:3365-3376.
5. Salehi B, Zucca P, Sharifi‚ÄźRad M, Pezzani R, Rajabi S, Setzer WN, et al. Phytotherapeutics in cancer invasion and metastasis. Phytother Res 2018; 32:1425-1449.
6. Sarwar MS, Zhang H-J, Tsang SW. Perspectives of plant natural products in inhibition of cancer invasion and metastasis by regulating multiple signaling pathways. Curr Med Chem 2018; 25:5057-5087.
7. Seo UK, Lee YJ, Kim JK, Cha BY, Kim DW, Nam KS, et al. Large-scale and effective screening of Korean medicinal plants for inhibitory activity on matrix metalloproteinase-9. J Ethnopharmacol 2005; 97:101-106.
8. Mykhailenko O, Lesyk R, Finiuk N, Stoika R, Yushchenko T, Ocheretniuk A, et al. In vitro anticancer activity screening of Iridaceae plant extracts. J Appl Pharm Sci 2020; 10:59-63.
9. Fouché G, Cragg G, Pillay P, Kolesnikova N, Maharaj V, Senabe J. In vitro anticancer screening of South African plants. J Ethnopharmacol 2008; 119:455-461.
10. Özdemir c, Alçitepe e, Sepet h. Morphological, anatomical and ecological studies of Gynandriris sisyrinchium L. Parl. in Turkey. Thaiszia J Bot 2011; 21:1-9.
11. El Shabrawy MOA, Marzouk MM, Kawashty SA, Hosni HA, El Garf IA, Saleh NAM. Flavonoids from Moraea sisyrinchium (L.) Ker Gawl.(Iridaceae) in Egypt. 2nd International Conference of Applied Life Sciences, Dubai, UAE, September 15-17, 2013; 33-37.
12. Al-Qudah MA, Saleh AM, Al-Jaber HI, Tashtoush HI, Lahham JN, Zarga MHA, et al. New isoflavones from Gynandriris sisyrinchium and their anti-oxidant and cytotoxic activities. Fitoterapia 2015; 107:15-21.
13. Al-Qudah MA, Muhaidat R, Trawenh IN. Volatile constituents of leaves and bulbs of Gynandriris sisyrinchium and their antimicrobial activities. Jordan J Chem 2012; 146:1-9.
14. Liu Z, Jiang Y, Yuan H, Fang Q, Cai N, Suo C, et al. The trends in incidence of primary liver cancer caused by specific etiologies: Results from the Global Burden of disease study 2016 and implications for liver cancer prevention. J Hepatol 2019; 70:674-683.
15. Taylor OG, Brzozowski JS, Skelding KA. Glioblastoma multiforme: An overview of emerging therapeutic targets. Front Oncol 2019; 9:963-974.
16. Witthayanuwat S, Pesee M, Supaadirek C, Supakalin N, Thamronganantasakul K, Krusun S. Survival analysis of glioblastoma multiforme. Asian Pac J Cancer Prev 2018; 19:2613-2617.
17. Beal EW, Tumin D, Kabir A, Moris D, Zhang X-F, Chakedis J, et al. Trends in the mortality of hepatocellular carcinoma in the United States. J Gastrointest Surg 2017; 21:2033-2038.
18. Präbst K, Engelhardt H, Ringgeler S, Hübner H. Basic colorimetric proliferation assays: MTT, WST, and resazurin.  Methods Mol Biol 2017; 1601:1-17.
19. Thorn CF, Oshiro C, Marsh S, Hernandez-Boussard T, McLeod H, Klein TE, et al. Doxorubicin pathways: Pharmacodynamics and adverse effects. Pharmacogenet Genomics 2011; 21:440-446.
20. Fares J, Fares MY, Khachfe HH, Salhab HA, Fares Y. Molecular principles of metastasis: A hallmark of cancer revisited. Signal Transduct Target Ther 2020; 5:1-17.
21. Deryugina EI, Bourdon MA, Luo G-X, Reisfeld RA, Strongin A. Matrix metalloproteinase-2 activation modulates glioma cell migration. J Cell Sci 1997; 110:2473-2482.
22. Du R, Petritsch C, Lu K, Liu P, Haller A, Ganss R, et al. Matrix metalloproteinase-2 regulates vascular patterning and growth affecting tumor cell survival and invasion in GBM. Neuro Oncol 2008; 10:254-264.
23. Kim YS, Li XF, Kang KH, Ryu B, Kim SK. Stigmasterol isolated from marine microalgae Navicula incerta induces apoptosis in human hepatoma HepG2 cells. BMB Rep 2014; 47:433-438.
24. Jiang CP, Ding H, Shi DH, Wang YR, Li EG, Wu JH. Pro-apoptotic effects of tectorigenin on human hepatocellular carcinoma HepG2 cells. World J Gastroenterol 2012; 18:1753-1764.
25. Yeh LT, Hsu LS, Chung YH, Chen CJ. Tectorigenin inhibits glioblastoma proliferation by G0/G1 cell cycle arrest. Medicina 2020; 56:681-690.