Differential effect of sanguinarine, chelerythrine and chelidonine on DNA damage and cell viability in primary mouse spleen cells and mouse leukemic cells

Abstract

Sanguinarine, chelerythrine and chelidonine are isoquinoline alkaloids derived from the greater celandine. They possess a broad spectrum of pharmacological activities. It has been shown that their anti-tumor activity is mediated via different mechanisms, which can be promising targets for anti-cancer therapy. We focused our study on the differential effects of these alkaloids upon cell viability, DNA damage effect and nucleus integrity in mouse primary spleen cells and mouse lymphocytic leukemic cells, L1210. Sanguinarine and chelerythrine produce a dose-dependent increase in DNA damage and cytotoxicity in both primary mouse spleen cells and L1210 cells. Chelidonine did not show a significant cytotoxicity or damage DNA in both cell types, but completely arrested growth of L1210 cells. Examination of nuclear morphology revealed more cells with apoptotic features upon treatment with chelerythrine and sanguinarine, but not chelidonine. In contrast to primary mouse spleen cells, L1210 cells showed slightly higher sensitivity to sanguinarine and chelerythrine treatment. This suggests that cytotoxic and DNA damaging effects of chelerythrine and sanguinarine are more selective against mouse leukemic cells and primary mouse spleen cells, whereas chelidonine blocks proliferation of L1210 cells. The action of chelidonine on normal and tumor cells requires further investigation.

Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives

“…Consistently, sanguinarine is a negative regulator of human epidermoid carcinoma cells (A431) but not of normal epidermal keratinocytes [23] . Evidence of this differential activity have been reported recently, showing that mouse lymphocytic leukemic cells are more sensitive to sanguinarine than normal splenocytes [99] . It is a matter of fact, however, that sanguinarine has been listed as responsible for the toxicity of Argemone mexicana seed oil [100][101][102] .…”

Antiproliferative and antiangiogenic effects of the benzophenanthridine alkaloid sanguinarine in melanoma

“…Authors have suggested that the cytotoxic and the DNA damaging effects of sanguinarine are selective against cancer cells as compared to normal cells [7,22], a finding, however, not confirmed by other studies [23]. We did not evaluate the effects of sanguinarine on normal melanocytes in the present work; while not addressing safety issues at this time, we believe, however, that properly designed in vitro and in vivo experiments are needed to exploit the undesired toxic effect of this alkaloid to normal tissue.…”

Surface-Enhanced Raman Spectroscopy (SERS) Tracking of Chelerythrine, a Na+/K+Pump Inhibitor, into Cytosol and Plasma Membrane Fractions of Human Lens Epithelial Cell Cultures

“…In the past, QBAs such as CET and its sister alkaloids, the sanguinarines, have been widely used as medicinal remedies in insecticides, bactericides, fungicides, viricides, in ointments, mouthwash solutions, and tooth pastes, sedatives and anti-helmintics [2]. More recently, CET had been first reported as a protein kinase C (PKC) inhibitor [3] and, utilizing this mechanism, later heralded as a potential anticancer agent capable of inducing apoptosis in a variety of cancer cell lines [4,5,6]. Acting as a BH3-mimetic, CET induces apoptosis by binding to BH1-like motifs of B cell lymphoma type 2 (Bcl-2) proteins inhibiting pro-survival B-cell lymphoma extra large (BclXI) proteins and activating mitochondrial Bcl-2 associated X (Bax)/ Bcl-2 homologous antagonist-killer (BAK) protein pro-apoptotic mechanisms [7,8,9].…”