Efficacy of Dequalinium Chloride vs Metronidazole for the Treatment of Bacterial Vaginosis: A Randomized Clinical Trial.

Importance: Bacterial vaginosis (BV) is a common cause of vaginal infection. First-line treatments of BV are metronidazole and clindamycin. Due to the increase in antibiotic resistance, effective nonantibiotic treatments for BV are needed. Objective: To examine whether dequalinium chloride, a broad-spectrum antiseptic, is noninferior to oral metronidazole for the treatment of BV. Design, Setting, and Participants: This phase 4, multicenter, triple-blind, double-dummy, parallel, noninferiority randomized clinical trial was conducted from July 29, 2021, to August 25, 2022, with a 1-month follow-up. Participants were premenopausal women 18 years or older with BV from 11 gynecologic practices and 1 hospital in Poland, Slovakia, and the Czech. Intervention: Patients were randomized to treatment with dequalinium chloride vaginal tablets (10 mg once daily for 6 days) or oral metronidazole (500 mg twice daily for 7 days). Double-dummy medication kits contained vaginal and oral tablets with placebo and active medication. Main Outcomes and Measures: The main outcome was the noninferiority margin (of 15 percentage points) in the absolute difference in clinical cure rates between dequalinium chloride and metronidazole 7 to 11 days after start of treatment (visit 1). Noninferiority was met if the lower 95% CI for the difference in clinical cure rate was less than 15 percentage points at visit 1. Results: A total of 147 women (mean [SD] age, 36.7 [9.0] years) were treated with dequalinium chloride (n = 72) or metronidazole (n = 75). The clinical cure rates at visit 1 were 64 of 69 (92.8%) for dequalinium chloride vs 69 of 74 (93.2%) for metronidazole in the intention-to-treat population, whereas in the per-protocol population, cure rates were 54 of 58 (93.1%) for dequalinium chloride vs 48 of 53 (90.6%) for metronidazole. The treatment differences of -0.5 percentage points (95% CI, -10.8 to 9.8 percentage points; P = .002) in the intention-to-treat population and 2.5 percentage points (95% CI, -9.4 to 14.4 percentage points; P = .001) in the per-protocol population confirmed the noninferiority of dequalinium chloride. The tolerability of dequalinium chloride was rated as very good by 30 of 50 patients (60.0%) but only by 21 of 54 (38.9%) for metronidazole. Three patients in the metronidazole group suspended treatment due to an adverse event. Conclusions and Relevance: This randomized clinical trial showed that dequalinium chloride was not inferior to metronidazole for the treatment of BV. Dequalinium chloride had a similarly high cure rate but with better tolerability and fewer adverse events. With a similar efficacy to metronidazole and clindamycin, dequalinium chloride warrants consideration as first-line treatment for BV to help reduce antibiotic consumption. Trial Registration: EudraCT: 2020-002489-15.

COMPARISON OF THE IMPACT OF ANTISEPTIC AGENTS ON GARDNERELLA VAGINALIS AND ATOPOBIUM VAGINAE DETECTED IN THE ORAL CAVITY OF WOMEN WITH BACTERIAL VAGINOSIS.

When women with comorbid bacterial vaginosis visit periodontologist, it is essential to understand the presence of cross-infection processes between the oral cavity and vagina in this particular category of subjects. Conducting detection of Gardnerella vaginalis and Atopobium vaginae, which are provocative microbial factors for bacterial vaginosis, is a mandatory step in the laboratory examination of subjects. When choosing an antiseptic for oral cavity disinfection, the use of 0.25% dequalinium chloride is more advisable. Both subjective and objective examination methods thoroughly demonstrate the higher clinical effectiveness of 0.25% dequalinium chloride: patients report a 20% more frequent improvement in subjective indicators, the index assessment of periodontal status improves by 1.2-1.6 times, and the detection rate of Gardnerella vaginalis and Atopobium vaginae is by 20% lower compared to 0.2% chlorhexidine. The specific composition of oral microbiota in this group of subjects necessitates adjustments to treatment protocols and consideration of the specific impact on Gardnerella vaginalis and Atopobium vaginae.

Dequalinium chloride use in adult Spanish women with bacterial vaginosis: an observational study.

Bacterial vaginosis (BV) represents the most frequent vaginal infection in women of childbearing age. The aim of this study was to characterise episodes of BV among adult Spanish women and their management with dequalinium chloride (DQC). Data from 573 DQC-treated BV adult women was obtained on medical records and questionnaires. The study shows that 20.6% had presented vaginal infections previously. Comorbid candidosis was significantly associated to other symptoms, such as pruritus or leucorrhoea. Most patients (64.3%) indicated a moderate-strong impact of the BV episode on their sexual life. After treatment, 84.8% of patients reported no BV symptoms. Patients were given instructions to prevent relapses. Most patients (83.1%) rated DQC as 'satisfactory' or 'very/extremely satisfactory' regarding symptom relief, prevention or treatment of the episode of BV. In conclusion, this study provides a better understanding of BV episodes and the impact of the treatment with DQC in real clinical practice in Spanish patients.IMPACT STATEMENTWhat is already known on this subject? Bacterial vaginosis (BV) is the most commonly reported vaginal infection among women of childbearing age. Despite the availability of antibiotic medications for the treatment of BV, management of this condition remains challenging. In fact, recurrence of BV has been reported for up to 50% of cases. However, antiseptic agents are considered an effective option for BV treatment.What the results of this study add? The study provides a better understanding of the prevalent symptomatology and the impact on quality of life of women with BV. Moreover, it has been observed that antiseptic dequalinium chloride (DQC) efficiently reduces symptoms and improves quality of life of the patients during episodes of BV.What the implications are of these findings for clinical practice and/or further research? In the context of the World Health Organisation recommendations on the rational use of antibiotics, we believe that the use of DQC may be a good alternative to antibiotics as a therapy for BV.

Vaginal tablets of dequalinium chloride 10 mg versus clotrimazole 100 mg for vaginal candidiasis: a double-blind, randomized study.

PURPOSE: To compare the clinical response, microscopic examination and fungal culture between dequalinium chloride (DQC) and clotrimazole (CT) for treating vaginal candidiasis (VC). METHODS: The double-blind, randomized study was conducted from September 2014 to September 2016 at Siriraj Hospital, Thailand. Eligible participants were Thai women diagnosed with VC by microscopic examination. The exclusion criteria included immunocompromised conditions, consumption of antifungal drugs, and having recurrent VC. Each participant was randomized with a 1:1 allocation to receive six vaginal tablets of 100 mg CT or 10 mg DQC. Two visits included 10 ± 2 days (C1) and 38 ± 4 days (C2). Outcome measures were improvement of VC symptoms, microscopic examination, culture, satisfaction and tolerability. RESULTS: Of 155 eligible participants, 150 were randomized and allocated into CT (N = 76) and DQC (N = 74). The average age was 31.1 ± 7.2 years. Comparable improvement of clinical response was demonstrated (OR at C1 0.79, 95% CI 0.56-1.10, p = 0.197; and OR at C2 0.99, 95% CI 0.69-1.43, p = 0.985). Of CT and DQC groups, the microscopic examination was positive at 11/75 (14.9%) vs 18/72 (25.3%) at C1 and 18/74 (24.3%) vs 28/66 (42.4%) at C2. And the culture was positive at 25/75 (33.8%) vs 46/72 (65.7%) at C1 and at 26/74 (36.6%) vs 46/66 (69.7%) at C2. Most participants had high satisfaction and tolerability and none reported any side effects. CONCLUSION: DQC and CT show comparable clinical response but CT results in greater improvement of microscopic examination and fungal culture. CLINICAL TRIAL REGISTRATION: The Clinical Trial Registry number was NCT02242695. (September 17, 2014).

ROS as a novel indicator to predict anticancer drug efficacy.

BACKGROUND: Mitochondria are considered a primary intracellular site of reactive oxygen species (ROS) generation. Generally, cancer cells with mitochondrial genetic abnormalities (copy number change and mutations) have escalated ROS levels compared to normal cells. Since high levels of ROS can trigger apoptosis, treating cancer cells with low doses of mitochondria-targeting / ROS-stimulating agents may offer cancer-specific therapy. This study aimed to investigate how baseline ROS levels might influence cancer cells' response to ROS-stimulating therapy. METHODS: Four cancer and one normal cell lines were treated with a conventional drug (cisplatin) and a mitochondria-targeting agent (dequalinium chloride hydrate) separately and jointly. Cell viability was assessed and drug combination synergisms were indicated by the combination index (CI). Mitochondrial DNA copy number (mtDNAcn), ROS and mitochondrial membrane potential (MMP) were measured, and the relative expression levels of the genes and proteins involved in ROS-mediated apoptosis pathways were also investigated. RESULTS: Our data showed a correlation between the baseline ROS level, mtDNAcn and drug sensitivity in the tested cells. Synergistic effect of both drugs was also observed with ROS being the key contributor in cell death. CONCLUSIONS: Our findings suggest that mitochondria-targeting therapy could be more effective compared to conventional treatments. In addition, cancer cells with low levels of ROS may be more sensitive to the treatment, while cells with high levels of ROS may be more resistant. Doubtlessly, further studies employing a wider range of cell lines and in vivo experiments are needed to validate our results. However, this study provides an insight into understanding the influence of intracellular ROS on drug sensitivity, and may lead to the development of new therapeutic strategies to improve efficacy of anticancer therapy.

Mitochondria-targeted delivery of doxorubicin to enhance antitumor activity with HER-2 peptide-mediated multifunctional pH-sensitive DQAsomes.

INTRODUCTION: Multidrug resistance (MDR) of breast cancer is the major challenge to successful chemotherapy while mitochondria-targeting therapy was a promising strategy to overcome MDR. MATERIALS AND METHODS: In this study, HER-2 peptide-PEG2000-Schiff base-cholesterol (HPSC) derivate was synthesized successfully and incorporated it on the surface of the doxorubicin (DOX)-loaded dequalinium (DQA) chloride vesicle (HPS-DQAsomes) to treat drug-resistant breast cancer. Evaluations were performed using human breast cancer cell and DOX-resistant breast cancer cell lines (MCF-7 and MCF-7/ADR). RESULTS: The particle size of HPS-DQAsomes was ~110 nm with spherical shape. In vitro cytotoxicity assay indicated that HPS-DQAsomes could increase the cytotoxicity against MCF-7/ADR cell line. Cellular uptake and mitochondria-targeting assay demonstrated that HPS-DQAsomes could target delivering therapeutical agent to mitochondria and inducing mitochondria-driven apoptosis process. In vivo antitumor assay suggested that HPS-DQAsomes could reach favorable antitumor activity due to both tumor targetability and sub-organelles' targetability. Histological assay also indicated that HPS-DQAsomes showed a strong apoptosis-inducing effect. No obvious systematic toxicity of HPS-DQAsomes could be observed. CONCLUSION: In summary, multifunctional HPS-DQAsomes provide a novel and versatile approach for overcoming MDR via mitochondrial pathway in cancer treatment.

Uso de probióticos en las vaginosis bacterianas / Use of probiotics in bacterial vaginosis

Introducción. La vaginosis bacteriana (VB) es una alteración de la microbiota vaginal por sobrecrecimiento bacteriano de los microorganismos habituales que produce síntomas de malestar vaginal, aumento de flujo vaginal maloliente, etc. Está en entredicho el papel de los probióticos en estas situaciones, aunque se ha visto en la práctica clínica que mejoran las tasas de recurrencias. Se presenta una revisión bibliográfica sobre la VB para valorar la efectividad del uso de probióticos como tratamiento adyuvante en VB. Método. Revisión en PubMed, Cochrane y SCOPUS de los últimos 5 años de las publicaciones que utilicen probióticos para el tratamiento de mujeres diagnosticadas de VB. Resultados. Se analizaron 10 artículos que hacen referencia al uso de probióticos en adición con tratamientos antibióticos. Conclusiones. Todos los artículos concluyen que el uso de probióticos es beneficioso en los casos de VB en adición a los tratamientos convencionales. No obstante, las conclusiones no son categóricas porque hay gran variedad de estudios y probióticos utilizados (AU)

Introduction. Bacterial vaginosis (BV) is a change in the vaginal microbiota due to bacterial overgrowth of normal microorganisms, which produces symptoms of vaginal discomfort, increased malodorous vaginal discharge, etc. Although they been seen to improve recurrence rates in clinical practice, the role of probiotics is questioned in these situations. A literature review on BV is presented in order to evaluate the effectiveness of using probiotics as adjuvant therapy in BV. Method. PubMed, Cochrane and SCOPUS review of the last 5 years publications using probiotics to treat women diagnosed with BV. Results. An analysis was performed on the 10 items that refer to the use of probiotics in addition to antibiotic treatments. Conclusions. All items conclude that the use of probiotics is beneficial in cases of BV in addition to conventional treatments. However, the conclusions are not categorical due to there being a wide variety of studies and probiotics used (AU)

Dequalinium for bacterial vaginosis.

Bacterial vaginosis is an infection characterised by overgrowth of anaerobic bacteria in the vagina with an accompanying loss of lactobacilli, and is thought to be the most common cause of abnormal vaginal discharge in women of child-bearing age.1 Standard treatment for symptomatic bacterial vaginosis consists of a short course of an oral or topical antibiotic.2 Dequalinium, a topical antiseptic agent, has been available for many years as a treatment for oral infections.3 A new formulation, dequalinium 10mg vaginal tablets (Fluomizin-Kora Healthcare), was licensed in the UK in June 2015 for the treatment of bacterial vaginosis.4 Here, we review evidence for the effectiveness and safety of dequalinium vaginal tablets in the management of bacterial vaginosis.

Manejo de la vaginosis bacteriana con cloruro de decualinio / No disponible

No disponible

Dequalinium blocks macrophage-induced metastasis following local radiation.

A major therapeutic obstacle in clinical oncology is intrinsic or acquired resistance to therapy, leading to subsequent relapse. We have previously shown that systemic administration of different cytotoxic drugs can induce a host response that contributes to tumor angiogenesis, regrowth and metastasis. Here we characterize the host response to a single dose of local radiation, and its contribution to tumor progression and metastasis. We show that plasma from locally irradiated mice increases the migratory and invasive properties of colon carcinoma cells. Furthermore, locally irradiated mice intravenously injected with CT26 colon carcinoma cells succumb to pulmonary metastasis earlier than their respective controls. Consequently, orthotopically implanted SW480 human colon carcinoma cells in mice that underwent radiation, exhibited increased metastasis to the lungs and liver compared to their control tumors. The irradiated tumors exhibited an increase in the colonization of macrophages compared to their respective controls; and macrophage depletion in irradiated tumor-bearing mice reduces the number of metastatic lesions. Finally, the anti-tumor agent, dequalinium-14, in addition to its anti-tumor effect, reduces macrophage motility, inhibits macrophage infiltration of irradiated tumors and reduces the extent of metastasis in locally irradiated mice. Overall, this study demonstrates the adverse effects of local radiation on the host that result in macrophage-induced metastasis.

The use of mitochondrial targeting resveratrol liposomes modified with a dequalinium polyethylene glycol-distearoylphosphatidyl ethanolamine conjugate to induce apoptosis in resistant lung cancer cells.

Intrinsic multidrug resistance (MDR) of cancers remains a major obstacle to successful chemotherapy. A dequalinium polyethylene glycol-distearoylphosphatidylethanolamine (DQA-PEG(2000)-DSPE) conjugate was synthesized as a mitochondriotropic molecule, and mitochondrial targeting resveratrol liposomes were developed by modifying DQA-PEG(2000)-DSPE on the surface of liposomes for overcoming the resistance. Evaluations were performed on the human lung adenocarcinoma A549 cells and resistant A549/cDDP cells, A549 and A549/cDDP tumor spheroids as well as the xenografted resistant A549/cDDP cancers in nude mice. The yield of DQA-PEG(2000)-DSPE conjugate synthesized was about 87% and the particle size of mitochondrial targeting resveratrol liposomes was approximately 70 nm. The mitochondrial targeting liposomes significantly enhanced the cellular uptake, and selectively accumulated into mitochondria when encapsulating coumarin as the fluorescent probe. Furthermore, mitochondrial targeting resveratrol liposomes induced apoptosis of both non-resistant and resistant cancer cells by dissipating mitochondria membrane potential, releasing cytochrome c and increasing the activities of caspase 9 and 3. They also exhibited significant antitumor efficacy in two kinds of cancer cells, in tumor spheroids by penetrating deeply into the core, and in xenografted resistant A549/cDDP cancers in nude mice. Mitochondrial targeting resveratrol liposomes co-treating with vinorelbine liposomes significantly enhanced the anticancer efficacy against the resistant A549/cDDP cells. In conclusion, mitochondrial targeting resveratrol liposomes would provide a potential strategy to treat the intrinsic resistant lung cancers by inducing apoptosis via mitochondria signaling pathway.

Selective targeting of neuroblastoma tumour-initiating cells by compounds identified in stem cell-based small molecule screens.

Neuroblastoma (NB) is the most deadly extra-cranial solid tumour in children necessitating an urgent need for effective and less toxic treatments. One reason for the lack of efficacious treatments may be the inability of existing drugs to target the tumour-initiating or cancer stem cell population responsible for sustaining tumour growth, metastases and relapse. Here, we describe a strategy to identify compounds that selectively target patient-derived cancer stem cell-like tumour-initiating cells (TICs) while sparing normal paediatric stem cells (skin-derived precursors, SKPs) and characterize two therapeutic candidates. DECA-14 and rapamycin were identified as NB TIC-selective agents. Both compounds induced TIC death at nanomolar concentrations in vitro, significantly reduced NB xenograft tumour weight in vivo, and dramatically decreased self-renewal or tumour-initiation capacity in treated tumours. These results demonstrate that differential drug sensitivities between TICs and normal paediatric stem cells can be exploited to identify novel, patient-specific and potentially less toxic therapies.

Plasmodium berghei: in vitro and in vivo activity of dequalinium.

Bisquinoline compounds have exhibited remarkable activity in vitro and in vivo against Plasmodium parasites by inhibition of heme detoxification. We have tested the ability of dequalinium 1,1'-(1,10-decanediyl)bis(4-amino-2-methylquinoline), a known antimicrobial agent, to inhibit beta-hematin synthesis using a non-emzymatic colorimetric assay and globin proteolysis by electrophoretic analysis (SDS-PAGE-15%). Dequalinium was able to inhibit both processes in vitro with close correlation to a murine malaria model, reducing parasitemia levels, prolonging the survival time post-infection and curing 40% of infected mice using a combination therapy with a loading dose of chloroquine. These results confirm that dequalinium is a promising lead for antimalarial drug development.

[Treatment of urogenital infections in lower part of the genital organs in pregnant women which are at risk of miscarriage].

Urogenital infection being one of etiological factor of the development of miscarriage, physicians regard carrying out complex microbiological diagnostics of pregnant women which are at risk of miscarriage to be very important as well as providing appropriate therapy for women with urogenital infection. The study aimed at investigating the efficacy of local antimicrobial medication Fluomisin in complex treatment of pregnant women which are at risk of miscarriage. Obtained results confirm Fluomisin to be effective, safe and convenient at use-for pregnant women with inferior urogenital infections.

Local treatment of vaginal infections of varying etiology with dequalinium chloride or povidone iodine. A randomised, double-blind, active-controlled, multicentric clinical study.

This randomised, double-blind, multicentric clinical study compared the efficacy and tolerability of the two vaginal antiseptics, 10 mg dequalinium chloride (CAS 522-51-0, Fluomycin N) and 200 mg povidone iodine (CAS 25655-41-8), in a parallel-group design. A total of 180 patients with vaginal infections of varying etiology participated in this study (bacterial vaginosis, fluor vaginalis, vulvo-vaginal candidiasis, trichomoniasis). Patients were randomly allocated to one of the two treatment groups and were treated once per day for 6 days. Control examinations took place 5 to 7 days after the end of treatment, and 3 to 4 weeks after the first control examination. The total symptoms score, a summary score for the clinical symptoms, discharge, burning, pruritus, redness of vulva/vagina, was defined as primary efficacy parameter. The treatments at the first control examination were compared in the full analysis set using the Wilcoxon-Mann-Whitney U-test, 2-sided, thereby proving equivalence of both treatments at the 5% level. Both treatments strongly improved the symptoms of vaginal infections both on short-term and long-term follow-up. Descriptive analysis of the secondary parameters, vaginal pH, degree of purity of the vaginal flora, and number of lactobacilli in the wet mounts, supported the comparable efficacy of both therapies to restore the vaginal milieu. Analysis of the diagnostic subgroups indicated that irrespective of the diagnosis, both treatments improved the efficacy criteria as observed for the entire population. The global assessment of the therapeutic efficacy by investigators and patients supported the results of the efficacy analysis with good to very good ratings in 70-90% of the cases. A good tolerability of both preparations was observed in this study with a low number of adverse events in the test group (5.8%).

Delocalized lipophilic cations selectively target the mitochondria of carcinoma cells.

Traditional chemotherapies, aimed at DNA replication in rapidly dividing cells, have achieved only limited success in the treatment of carcinomas due largely to their lack of specificity for cells of tumorigenic origin. It is important, therefore, to investigate treatment strategies aimed at novel cellular targets that are sufficiently different between normal cells and cancer cells so as to provide a basis for selective tumor cell killing. Delocalized lipophilic cations (DLCs) are concentrated by cells and into mitochondria in response to negative inside transmembrane potentials. The higher plasma and/or mitochondrial membrane potentials of carcinoma cells compared to normal epithelial cells account for the selective accumulation of DLCs in carcinoma mitochondria. Since most DLCs are toxic to mitochondria at high concentrations, their selective accumulation in carcinoma mitochondria and consequent mitochondrial toxicity provide a basis for selective carcinoma cell killing. Several of these compounds have already displayed some degree of efficacy as chemotherapeutic agents in vitro and in vivo. The effectiveness of DLCs can also be enhanced by their use in photochemotherapy or combination drug therapy. Discovery of the biochemical differences that account for the higher membrane potentials in carcinoma cells is expected to lead to the design of new DLCs targeted specifically to those differences, resulting in even greater selectivity and efficacy for tumor cell killing.

[Microbiology of acute pharyngitis and acute tonsillitis and treatment with Taileqi troches].

A qualitative analysis of microflora from pharynx of 100 cases of acute pharyngitis and acute tonsillitis was performed. These patients were randomly divided into two groups so as to assess treatment effect of Taileqi troches vs Amoxycillin. Results showed that beta-hemolytic streptococcus, Klebsiella pneumoniae, staphylococcus aureus were the most common organisms causing diseases. The predominant anaerobic organisms were bacteroides melaninogenicus, eptostrep. These findings suggest that anaerobic bacteria may play a pathogenic role in infection of the pharynx. The effective rate of treatment with troche alone were 86 percent, roughly consistent with Amoxycillin group. No adverse effect was observed.

Failure to enhance the in vivo killing of human ovarian carcinoma by sequential treatment with dequalinium chloride and tumor necrosis factor.

Dequalinium chloride (DECA) is a cationic, lipophilic compound with structure similar to the dye rhodamine 123. DECA is selectively accumulated and retained within the mitochondria of carcinoma cells where it acts as a mitochondrial poison by blocking mitochondrial enzymes which can then disrupt cellular energy production, eventually resulting in cell death. In this manner it is similar to the antimitochondrial effects observed with tumor necrosis factor (TNF). We have previously shown that DECA can synergize the in vitro antitumor effects of TNF against a panel of human ovarian cancer cell lines. Those drug studies have been extended to a xenogenic tumor system with a resultant increase in animal survival. Athymic mice were injected intraperitoneally with 2.0 x 10(7) PA-1 human ovarian cancer cells and DECA +/- TNF treatments begun either on Days 3 or 7 postinjection. Peritoneal tumor implantation was not histologically confirmed by Day 3 postinjection but confirmed by Day 7 following tumor cell injection. Single-agent DECA (5 mg/kg; qod) increased animal survival by 37% (P = 0.002) whereas recombinant human TNF (0.5 micrograms/mouse; qod) only increased survival by 13% (P = 0.27) relative to control animals for those animals treated 3 days post-tumor-injection. Sequential DECA/TNF enhanced animal survival by 45% (P = 0.0002) in similarly treated animals. When drug treatment was initiated 7 days following tumor injection, DECA increased survival by 23% (P = 0.04) while TNF had no effect on prolonging animal survival (3% increase; P = 0.79). Combination DECA/TNF increased survival by 23% (P = 0.04). In the UCI-101 ovarian tumor model, single-agent DECA increased survival by 28% (P = 0.04) while TNF treatment stimulated tumor growth (11% decrease in survival; P = 0.006). Combination DECA + TNF resulted in a 41% increase in survival (P = 0.003). No statistical differences were detected between survival rates for single-agent DECA vs DECA + TNF except for the UCI-101 tumor which showed potentiation due to the in vivo stimulatory effects of TNF.

Effect of dequalinium on K1735-M2 melanoma cell growth, directional migration and invasion in vitro.

Cationic lipophilic compounds have an antiproliferative effect on certain tumour systems in vitro and in vivo. We have investigated whether the cationic lipophilic compound dequalinium affects not only proliferation but also motility and invasion of the highly metastatic and highly invasive melanoma cell line K1735-M2. Proliferation was assessed in monolayer cultures and in multicellular spheroids, motility was estimated in the assay of directional migration, and invasiveness was tested through confrontation cultures of tumour multicellular spheroids with embryonic chick heart tissue evaluated by computerized image analysis. 2 mumol/l dequalinium impaired melanoma cell proliferation, reduced directional migration and significantly blocked invasion in vitro. On the ultrastructural level, dequalinium caused obvious changes in mitochondria of both melanoma and embryonic chick heart cells. The mechanisms of the antiproliferative, antimigrating and antiinvasive effects remain to be determined. Inhibition of protein kinase C, calmodulin antagonism, DNA intercalation and/or direct effects on mitochondrial functions may be considered.