Sanguinarine Chloride Research Articles

Combination analyses of anti-cancer drugs on human neuroendocrine tumor cell lines

There is a large need for better pharmacological treatment of neuroendocrine tumors. The aim of this study was to investigate and quantify the cytotoxic potentiating effects resulting from a combination of five substances, NSC 95397, emetine, CGP-74514A hydrochloride, Brefeldin A and sanguinarine chloride, chosen from a previous screening of 1,280 pharmacologically active agents on neuroendocrine tumor cells, with standard cytotoxic agents currently used in the treatment of neuroendocrine tumors. The human pancreatic carcinoid cell line BON-1, human typical bronchial carcinoid cell line NCI-H727 and the human atypical bronchial carcinoid cell line NCI-H720 were used. Combinations between doxorubicin, etoposide, oxaliplatin, docetaxel, and each one of the five agents were studied and simultaneous exposures were explored using the median-effect method. Most of the combinations of NSC-95397 and emetine with doxorubicin, etoposide, docetaxel, and oxaliplatin showed synergism, and their remaining combinations were additive. Almost all of the CGP-74514A hydrochloride interactions were additive, while brefeldin A and sanguinarine displayed less synergy but more additive and antagonistic interactions in combination with the standard drugs. The synergistic and additive interactions make NSC-95397, emetine, and CGP-74514A hydrochloride potential candidates for incorporation into combination chemotherapy regimens and these drugs might be the suitable candidates for further clinical studies in patients with bronchial carcinoids and pancreatic endocrine tumors.

SOS induction of selected naturally occurring substances in Escherichia coli (SOS chromotest)

Naturally occurring substances were tested for genotoxicity using a modified laboratory protocol of the Escherichia coli PQ37 genotoxicity assay (SOS chromotest) in the presence and in the absence of an exogenous metabolizing system from rat liver S9-mix. Aristolochic acid I, II, the plant extract aristolochic acid and psoralene were genotoxic; cycasine, emodine, monocrotaline and retrorsine were classified as marginal genotoxic in the SOS chromotest in the absence of S9-mix. In the presence of an exogenous metabolizing system from rat liver S9-mix aristolochic acid I, the plant extract, β-asarone, cycasin, monocrotaline, psoralen and retrorsine showed genotoxic effects; aristolochic acid II marginal genotoxic effects. Arecoline, benzyl acetate, coumarin, isatidine dihydrate, reserpine, safrole, sanguinarine chloride, senecionine, senkirkine, tannin and thiourea revealed no genotoxicity in the SOS chromotest either in the presence or in the absence of an exogenous metabolizing system from rat liver S9-mix. For 17 of 20 compounds, the results obtained in the SOS chromotest could be compared to those obtained in the Ames test. It was found that 12 (70.6%) of these compounds give similar responses in both tests (6 positive and 6 negative responses). The present investigation and those reported earlier, the SOS chromotest, using E. coli PQ37, was able to detect correctly most of the Salmonella mutagens and non-mutagens.

In vitro activities of antimicrobial agents against Candida species

Objective. Antimicrobial mouthrinses may represent a valid alternative to topical antifungal agents. However, the action of antimicrobials could be affected by the different ingredients incorporated into mouthrinse products. The purpose of the present study was to investigate the in vitro antifungal and fungicidal activities of antimicrobials alone. Study Design. A broth macrodilution method was used to determine the minimum inhibitory concentration of 4 antimicrobial agents against Candida species. Minimum fungicidal concentration was also determined. Results. All antimicrobials showed antifungal activity against all tested organisms, but cetylpyridinium chloride received significantly lower minimum inhibitory concentrations ( P < .005). Cetylpyridinium chloride also showed a greater fungicidal activity than chlorhexidine digluconate and hexetidine ( P < .005), whereas sanguinarine chloride appeared to be less fungicidal against most of the isolates tested. Conclusions. These findings suggest that cetylpyridinium chloride may be used as a topical antifungal agent. Clinical trials are now required to assess its value in the management of oral candidosis.(Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:44-9)

Cytotoxicity of sanguinarine chloride to cultured human cells from oral tissue.

The in vitro cytotoxicity of sanguinarine chloride, a dental product used in the treatment of gingivitis and plaque, was compared using cell lines and primary cells from oral human tissues. For the established cell lines, sanguinarine chloride exhibited similar potencies to S-G gingival epithelial cells and to KB carcinoma cells, whereas HGF-1 gingival fibroblasts were more tolerant. However, a gingival primary cell culture was more sensitive to sanguinarine chloride than were the established cell lines. Detailed studies were performed with the S-G cells. The 24-hr midpoint (NR50) cytotoxicity value towards the S-G cells was 7.6 microM, based on the neutral red cytotoxicity assay; vacuolization and multinucleation were noted. When exposed to sanguinarine chloride for 3 days, a lag in growth kinetics was first observed at 1.7 microM. Damage to the integrity of the plasma membrane was evident, as leakage of lactic acid dehydrogenase occurred during a 3 hr exposure to sanguinarine chloride at 0.1275 mM and greater. The cytotoxicity of sanguinarine chloride to the S-G cells was lessened in the presence of an S9 hepatic microsomal fraction from Aroclor-induced rats or by including fetal bovine serum (15%) in the exposure medium. Progressively increasing the pH from 6.0 to 7.8 enhanced the potency of sanguinarine chloride, presumably due to the enhanced uptake of the lipophilic alkanolamine form, as compared to that of the cationic iminium form.

Sanguinarine, a phototoxic H2O2-producing alkaloid.

Sanguinarine chloride, a quaternary salt of a benzophenanthrene alkaloid, was phototoxic to catalase-deficient strains of Escherichia coli but not to Trichoplusia ni (cabbage looper moth larvae), an insect with high levels of catalase activity. Chemical analyses confirm that sanguinarine is an efficient producer of H2O2. This differential toxicity suggests that the mode of phototoxic action involves production of H2O2 which could be detoxified in many organisms by catalase.

1,2-Dihydroisoquinolines. Part XIII. Synthesis of sanguinarine chloride

The first synthesis of sanguinarine chloride (2,3:7,8-bismethylenedioxybenzo[c]phenanthridine methochloride), from 2-hydroxy-3-methoxybenzaldehyde, is described.