Sanguinarine: a monofunctional intercalating alkaloid

Maiti, Motilal; Nandi, R.; Chaudhuri, Keya

doi:10.1016/0014-5793(82)80152-x

Cited by 98 publications

(47 citation statements)

References 12 publications

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“…During a cellular screening of benzophenanthridine alkaloids we found that the drug resulted more active than the analogous compound cheleritrine against the murine cell line B16 melanoma 4A5, and that it mainly acts as an intercalating agent producing DNA breaks. This finding is in keeping with earlier data from Maiti and colleagues [21], showing that sanguinarine strongly interacts with DNA, binding, like ethidium bromide, by monofunctional mode of intercalation. Importantly, previous…”

Section: Discussionsupporting

confidence: 92%

Antiproliferative and antiangiogenic effects of the benzophenanthridine alkaloid sanguinarine in melanoma

Stefano

Raspaglio

Zannoni

et al. 2009

Biochemical Pharmacology

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This study was aimed at evaluating the potential application of benzophenanthridine alkaloids, sanguinarine and cheleritrine, in the therapy of melanoma cancer. In vitro antiproliferative activity of sanguinarine was higher than that of cheleritrine against the B16 melanoma 4A5 cells. Both agents were able to produce DNA breaks, and the DNA unwinding assay showed that they act as DNA intercalating agents. Sanguinarine was selected for determination of its in vivo preclinical efficacy. Oral treatment with sanguinarine reduced the tumor burden in a transplantable murine tumor grown in a syngenic host (B16 melanoma 4A5 in C57BL/6 mice), and in a human tumor xenograft grown in immunodeficient mice (A375 human melanoma in athymic nude mice). In A375 tumors a significant decrease in the proliferation marker Ki67, and a reduction in the activated mitogen-activated protein kinases (p-p44/42 MAPK), and in protein kinase B (pAKT) were also observed. Three out of eleven A375-bearing treated mice were tumor-free at the end of treatment, and did not develop any tumor after a further, treatment-free, observation period of 60 days. Sanguinarine also showed a striking anti-angiogenic activity in mice. Data from the present study support the concept that sanguinarine can be effective in melanoma skin cancer.

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Section: Discussionsupporting

confidence: 92%

Antiproliferative and antiangiogenic effects of the benzophenanthridine alkaloid sanguinarine in melanoma

Stefano

Raspaglio

Zannoni

et al. 2009

Biochemical Pharmacology

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“…The results of our experiments together with informations in the literature [7][8][9] about the mode of interaction of the alkaloids with DNA clearly show that intact alkaloids interact with DNA solely noncovalently by forming a kinetically labile complex. The contradictory arguments reported in the literature suggesting other modes of interaction [10][11][12][13][14] are probably a consequence of metabolic activation of the alkaloids inside the living organisms.…”

Section: Resultsmentioning

confidence: 63%

“…Again each alkaloid was mixed with DNA in this buffer and the respective blank mixture (containing the DNA only) was prepared for comparison. The concentration of DNA in terms of nucleotides calculated using the molar absorption coefficient of 6600 M 21 cm 21 [7], the tabulated absorbance 20 AU/mg solid (from the certificate of analysis of Sigma-Aldrich) was 1 M, and the concentration of the alkaloid was 25 mM. The repeated analysis of the aliquots of these mixtures being kept at room temperature for 48 h did not reveal any covalent product expressed as an additional peak in the respective electropherograms.…”

Section: Resultsmentioning

confidence: 99%

“…For example, the interaction of various QIAs with DNA has been repeatedly investigated and intercalation was concluded as the mode of interaction in most of the studies [7][8][9]. However, this mechanism cannot entirely explain all known facts about the alkaloids' action in biological systems, such as the mutagenic action being reported for sanguinarine (SA) [10] and chelerythrine (CHE) [11] as the most important quaternary benzo[c]-phenanthridine alkaloids as well as for berberine (BE) [12], the most important quaternary protoberberine alkaloid.…”

Section: Introductionmentioning

confidence: 99%

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Capillary zone electrophoretic studies of interactions of some quaternary isoquinoline alkaloids with DNA constituents and DNA

et al. 2005

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Capillary zone electrophoresis was applied for the investigation of interactions of some quaternary isoquinoline alkaloids, namely sanguinarine, chelerythrine, berberine, and jatrorrhizine, with DNA constituents and with DNA. None of these alkaloids attach covalently to nucleotides or to the whole DNA under physiological conditions. The interaction with DNA constituents is a noncovalent complexation based on weak intermolecular forces. Electrostatic attraction participates in the interaction but other types of intermolecular forces are involved as well. Cations were identified as the most probable interacting forms of the alkaloids. The interaction with compounds derived from purine was always stronger than those derived from pyrimidine. All alkaloids behaved analogously and similarly to ethidium bromide, the classic DNA intercalator. Stability constants K (in l.mol(-1)) for sanguinarine and chelerythrine in phosphate buffer of pH 7.4 (I(S) = 30 mM) ranged from tens to hundreds.

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“…5 It has been reported that sanguinarine iminium group binds to ␤-form duplex DNA by the mechanism of intercalation with a high preference to G-C base pairs while the sanguinarine alkanolamine form does not bind to DNA. 31,32 However sanguinarine chloride failed to reveal genotoxicity in SOS chromtest using E. coli PQ37 in the absence and presence of metabolic activitation system. 33 Further, studies of Damm et al 34 raised the possibility of usage of Sanguinaria extract in the development of oral leukoplakia, which have been refuted by Munro et al 35 In our study, the distribution of cells in 2-and 4-tail moment category were more in controls as compared to argemone oil-treated animals, while in 6, 8, 10 and Ͼ 10-tail moment category, the cells were more in argemone oil compared to controls, suggesting that greater DNA damage occurred following the higher dose of argemone oil treatment, which reaffirms the genotoxic potential of argemone oil.…”

Section: Discussionmentioning

confidence: 99%