Correlation of the cytotoxic activity of four different alkaloids, from Chelidonium majus (greater celandine), with their DNA intercalating properties and ability to induce breaks in the DNA of NK/Ly murine lymphoma cells

Abstract

Abstract:The purpose of this study was to examine the relationship between the DNA intercalating characteristics and the DNA damaging capacity of four alkaloids extracted from Chelidonium majus L, as well as their toxicity towards murine NK/Ly lymphoma cells. Chelerythrine, sanguinarine and coptisine were found to be intercalated into the DNA isolated from NK/Ly cells, meanwhile, chelidonine exhibited no affinity to DNA. Sanguinarine exhibited the greatest toxicity toward NK/Ly cells, and the toxicity of the other three decreased in descending order: chelerythrine, coptisine and chelidonine. Chelerythrine and sanguinarine caused DNA damage, illustrated by the formation of comets of the third class. Coptisine was less toxic than chelerythrine and sanguinarine, and affected the formation the same class of comets in higher concentration. The quantity of comets induced by chelidonine were negligible, a finding consistent with its inability to intercalate into DNA structure. The ability of four main alkaloids of Chelidonium majus L., to intercalate into DNA isolated from murine NK/Ly lymphoma cells, correlated with their ability to induce breaks in cellular DNA and with their toxic effect towards those cells.

Chelidonium majus L. (Greater celandine) – A Review on its Phytochemical and Therapeutic Perspectives

“…In addition to these, plant also contains different aromatic and aliphatic acids such as chelidonic acid (51), caffeic acid (52), ferulic acid (53), pcoumaric acid (54), citric acid (55), malic acid (56), succinic acid (57), gentisic acid (58), p-hydroxybenzoic acid (59) and nicotinic acid (60) [11,12] . Recently four caffeic acid esters such as 2-(-)-caffeoyl-D-glyceric acid (61), 4-(-)-caffeoyl-Lthreonic acid (62), (+)-caffeoyl-L-malic acid (63) and 2-(-)-caffeoyl-L-threonic acid lactone (64) have been identified [13] . Besides, it contains lesser amount of phytosterols [α-spinasterol (65) (72), tyramine (73), histamine (74) and saponosides [12,[14][15][16] .…”

“…The extract of C. majus was reported to possess anticancer potentials against variety of chemical carcinogens and inhibited carcinogen-induced angiogenesis and fibroblast proliferation [63] . Several reports demonstrated the anticancer potential of various C. majus alkaloids such as chelidonine, sanguinarine, berberine, chelerythrine and coptisine [64,65] . Chelidonine and sanguinarine induced apoptosis in human lymphoblastic leukaemia cells via caspase 9 and 3 activation and an increase of pro-apoptotic Bax protein [65] .…”

Hepatotoxic Botanicals - An Evidence-based Systematic Review

“…The woman stopped taking greater celandine but continued with other medications and she recovered (86). Moreover, greater celandine showed to cause phototoxicity and cytotoxicity on cancer cells (87,88).…”

Study of morphological changes in mammalian cell lines under action of medicinal herb extracts in vitro

“…У дослідженнях від-значено спорідненість сангвінарину до ДНК. Досліджено протипухлинний ефект сангвінарину як найбільш активного алкалоїду чистотілу [6,7]. Народна медици-на рекомендує Рotentilla erecta як протипухлинний засіб.…”

“…Катіони сангвінарину здатні: 1) інтеркалювати у двоспіральні ДНК, РНК та інгібувати реакції, що відбуваються на ДНК та РНК як матриці; 2) порушують синтез АТФ у мітохондріях завдяки нейтралізуванню негативних зарядів зовніш-нього боку мембран мітохондрій, що виникають при їх енергізації; 3) модифікують тіолові групи органічних сполук завдяки реакції нуклеофільного заміщення при взаємодії тіолових груп органічних речовин з імінною групою; 4) інгібують фермен-ти лізосом [4,14]. Порівнюючи власні отримані результати дослідження з літера-турними даними [6,7], можна зробити висновок, що саме сангвінарин є основним діючим компонентом екстракту перстачу, який спричиняє апоптоз.…”