Melanoma is a cancer of melanocyte cells and has the highest global incidence. There is a need to develop new drugs for the treatment of this deadly cancer, which is resistant to currently used treatment modalities. We investigated the anticancer activity of visnagin, a natural furanochromone derivative, isolated from Ammi visnaga L., against malignant melanoma (HT 144) cell lines. The singlet oxygen production capacity of visnagin was determined by the RNO bleaching method while cytotoxic activity by the MTT assay. Further, HT 144 cells treated with visnagin were also exposed to visible light (λ ≥ 400 nm) for 25 min to examine the illumination cytotoxic activity. The apoptosis was measured by flow cytometry with annexin V/PI dual staining technique. The effect of TNF-α secretion on apoptosis was also investigated. In standard MTT assay, visnagin (100 µg/mL) exhibited 80.93% inhibitory activity against HT 144 cancer cell lines, while in illuminated MTT assay at same concentration it showed lesser inhibitory activity (63.19%). Visnagin was induced apoptosis due to the intracellular generation of reactive oxygen species (ROS) and showed an apoptotic effect against HT 144 cell lines by 25.88%. However, it has no effect on TNF-α secretion. Our study indicates that visnagin can inhibit the proliferation of malignant melanoma, apparently by inducing the intracellular oxidative stress.
Visnagin Ammi visnaga L. Malignant melanoma Apoptosis
This is a preview of subscription content, log in to check access.
This study is a part of F.A.Ö’s Ph.D. thesis and was supported by the Research Fund of Istanbul University (Project Number: TP-19969). Prof. Dr. KerimanGünaydın would like to thank all staff of the Dr. Panjwani Center for Molecular Medicine and Drug Research (ICCBS), University of Karachi, Pakistan, for providing research facilities for her studies.
Compliance with ethical standards
Conflict of interest
The authors declare that is no conflicts of interest associated with this publication.
Bamhill RL, Fandrey K, Levy MA, Mihm ML, Hyman B (1992) Angiogenesis and tumor progression of melanoma. Quantification of vascularity in melanocytic nevi and cutaneous malign melanoma. Lab Invest 67:331–337Google Scholar
Watson M (2012) Drugs in clinical development for melanoma: summary and table. Pharm Med 26:171–183CrossRefGoogle Scholar
Rogers HW, Weinstock MA, Hinckley MR, Feldman SR, Fleischer AB, Coldiron BM (2010) Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol 146:283–287CrossRefGoogle Scholar
Matsuo Y, Kamitani T (2010) Parkinson’s disease-related protein, a-synuclein, in malignant melanoma. PLoS ONE 5:1–8Google Scholar
Disse M, Reich H, Lee PK, Schram SS (2016) A review of the association between parkinson disease and malignant melanoma. Dermatol Surg 42:141–146CrossRefGoogle Scholar
Batistatou A, Cook MG, Massi D (2009) Histopathology report of cutaneous melanoma and sentinel lymph node in Europe: a web-based survey by the Dermatopathology Working Group of the European Society of Pathology. Virchows Arch 454:505–511CrossRefGoogle Scholar
Gunaydin K, Beyazit N (2004) The chemical investigations on the ripe fruits of Ammi visnaga (Lam.) Lamarck growing in Turkey. Nat Prod Res 18:169–175CrossRefGoogle Scholar
Rauwald HW, Brehm O, Odenthal KP (1994) The Involvement of a Ca2+ channel blocking mode of action in the pharmacology of Ammi visnaga fruits. Planta Med 60:101–105CrossRefGoogle Scholar
Martelli P, Bovalini L, Fe S, Franchi GG, Bari M (1985) Active oxygen forms in photoreaction between DNA and furanochromones khellin and visnagin. FEBS Lett 189:255–257CrossRefGoogle Scholar
Chen X, Kagan J (1993) Photosensitized cleavage and cross-linking of pBR322 DNA with khellin and visnagin. J Photochem Photobiol B 20:183–189CrossRefGoogle Scholar
Cuong TD, Lim CJ, Kim SW, Park JE, Hung TM, Min BS (2011) Isolation of compounds from Cimicifugae Rhizoma and their cytotoxic activity. Nat Prod Sci 17:80–84Google Scholar
El-Nakkady SS, Roaiah HF, El-Serwy WS, Soliman AM, El-Moez SIA, Abdel-Rahman AA-H (2012) Antitumor and antimicrobial activities of some hetero aromatic benzofurans derived from naturally occurring visnagin. Acta Pol Pharm 69:645–655Google Scholar
Pakfetrat H, Nemati N, Shiravi A (2015) Cytotoxicity effects of Ammi visnaga extract on Hela and MCF-7 cancer cell line. Anim Biol 7:25–33Google Scholar
Kraljic I, Mohsni S (1978) A new method for the detection of singlet oxygen in aqueous solutions. Photochem Photobiol 28:577–581CrossRefGoogle Scholar
Aydoğmuş-Öztürk F, Günaydin K, Öztürk M, Jahan H, Duru ME, Choudhary MI (2018) Effect of Sideritis leptoclada against HT-144 human malignant melanoma. Melanoma Res 28:502–509CrossRefGoogle Scholar
Wu D, Yotnda P (2011) Production and detection of reactive oxygen species (ROS) in cancer. J Vis Exp 57:1–4Google Scholar
Jahan H, Choudhary MI, Shah Z, Khan KM (2017) Derivatives of 6-nitrobenzimidazole inhibit fructose-mediated protein glycation and intracellular reactive oxygen species production. Med Chem 13:577–584CrossRefGoogle Scholar
Vermes I, Haanen C, Steffensnakken H, Reutelingsperger C (1995) A novel assay for apoptosis-flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein-labeled annexin-V. J Immunol Methods 184:39–51CrossRefGoogle Scholar
Iram N, Mildner M, Prior M, Petzelbauer P, Fiala C, Hacker S, Schoppl A, Tschachler E, Elbe-Burger A (2012) Age-related changes in expression and function of Toll-like receptors in human skin. Development 139:4210–4219CrossRefGoogle Scholar
Bristow MR, Mason JW, Billingham ME, Daniels JR (1978) Doxorubicin cardiomyopathy: evaluation by phonocardiography, endomyocardial biopsy, and cardiac catheterization. Ann Intern Med 88:168–175CrossRefGoogle Scholar
Xi L (2016) Visnagin—a new protectant against doxorubicin cardiotoxicity? Inhibition of mitochondrial malate dehydrogenase 2 (MDH2) and beyond. Ann Transl Med 4:65–69CrossRefGoogle Scholar
Sayed H, Mohamed MH, Farag SF, Mohamed GA, Proksch P (2007) A New Steroid Glycoside and Furochromones from Cyperus rotundus L. Nat Prod Res 21:343–350CrossRefGoogle Scholar
Beltagy AM, Beltagy DM (2015) Chemical composition of Ammi visnaga L. and new cytotoxic activity of its constituents khellin and visnagin. J Pharm Sci Res 7:285–291Google Scholar
Circu ML, Aw TY (2010) Reactive oxygen species, cellular redox system and apoptosis. Free Radic Biol Med 48:749–762CrossRefGoogle Scholar
Matthews N, Neale ML, Jackson SK, Stark JM (1987) Tumour cell killing by tumour necrosis factor: inhibition by anaerobic conditions, free-radical scavengers and inhibitors of arachidonate metabolism. Immunology 62:153–155Google Scholar