Lomefloxacin Induces Oxidative Stress and Apoptosis in COLO829 Melanoma Cells

Although some fluoroquinolones have been found to exert anti-tumor activity, studies on the effect of these drugs on melanoma cells are relatively rare. The aim of this study was to examine the effect of lomefloxacin on cell viability, reactive oxygen species production, redox balance, cell cycle distribution, DNA fragmentation, and apoptosis in COLO829 melanoma cells. Lomefloxacin decreases the cell viability in a dose- and time-dependent manner. For COLO829 cells treated with the drug for 24, 48, and 72 h, the values of IC50 were found to be 0.51, 0.33, and 0.25 mmol/L, respectively. The analyzed drug also altered the redox signaling pathways, as shown by intracellular reactive oxygen species overproduction and endogeneous glutathione depletion. After lomefloxacin treatment, the cells were arrested in S- and G2/M-phase, suggesting a mechanism related to topoisomerase II inhibition. DNA fragmentation was observed when the cells were exposed to increasing lomefloxacin concentrations and a prolongation of incubation time. Moreover, it was demonstrated that the drug induced mitochondrial membrane breakdown as an early hallmark of apoptosis. The obtained results provide a strong molecular basis for the pharmacologic effect underlying the potential use of lomefloxacin as a valuable agent for the treatment of melanoma in vivo

The role of protective agents in pharmacotherapy- assessment of patients awareness

SUBJECT OF THE STUDY: The use of medication is associated with the risk of side effects. In the view of the fact that the consumption of Nonsteroidal anti-inflammatory drugs (NSAIDs) and antibiotics is growing constantly, it is necessary to apply appropriate protection strategies to prevent side-effects of those drugs. AIM OF THE STUDY: The aim of the study is to asses patients' knowledge about protective agents: drugs that reduce the production of hydrochloric acid from the group of proton pump inhibitors and probiotics in the terms of effectiveness and safety of, respectively, inflammations and the bacterial infections pharmacotherapy. MATERIAL AND METHODS: The research was carried out since October 2018 to February 2019 on the random group of people from Poland, using an original, anonymous questionnaire. The data was collected via Internet and direct contact with the respondents participating classes at the University of Third Age of the Medical University of Silesia. The statistical analysis of the collected results was performed with the use of Microsoft Excel 2010. RESULTS: Almost everyone of the respondents (about 95.0%) think that they understand the concept of a protective agents. Many of them only associates them with antibiotic therapy, not being aware of the broader meaning of this concept. 82.0% of respondents believe that they know the concept of a probiotic, but as many as 64.6 % of patients mistakenly think, that probiotics protect the stomach. About 50.0% of people are aware of the need to protect the stomach with chronic Nonsteroidal anti-inflammatory drugs therapy. CONCLUCIONS: The obtained results show that patients have basic information about gastro-enteroprotective agents (including drugs that reduce the production of hydrochloric acid from the group of proton pump inhibitors and probiotics) however their knowledge is still insufficient to guarantee the effectiveness of therapy. The further education is necessary, which could be improved by introducing the Pharmaceutical Care.PRZEDMIOT BADAŃ: Stosowanie każdego rodzaju leków wiąże się z ryzykiem wystąpienia działań niepożądanych. W świetle rosnącego spożycia leków przeciwbólowych i antybiotyków konieczne staje się stosowanie właściwych strategii ochronnych, zapobiegających ubocznym skutkom działania tych leków. CEL BADAŃ: Celem pracy jest zbadanie wiedzy pacjentów na temat preparatów osłonowych, w szczególności leków zmniejszających produkcję kwasu solnego z grupy inhibitorów pompy protonowej oraz probiotyków. MATERIAŁ I METODY: Badanie przeprowadzono od października 2018 do lutego 2019 na losowej grupie 582 mieszkańców Polski za pomocą autorskiego, anonimowego kwestionariusza ankiety. Analizę statystyczną zebranego materiału, wykonano za pomocą programu Microsoft Excel 2010. WYNIKI: W badaniu 94,5% ankietowanych zadeklarowało, że rozumie pojęcie preparatu osłonowego. Duży odsetek grupy badanej wiąże je jedynie z antybiotykoterapią, nie mając świadomości szerszego znaczenia tego pojęcia. 82,0% respondentów uważa, że zna pojęcie probiotyku, jednak aż 64,6% z nich niewłaściwie zastosowałoby probiotyk jako osłonę żołądka. Niespełna 50,0% osób ma świadomość konieczności ochrony żołądka przy przewlekłej terapii lekami z grupy niesteroidowych leków przeciwzapalnych. WNIOSKI: Przeprowadzone badanie wykazało, że ankietowani posiadają podstawową wiedzę na temat preparatów osłonowych jednak nie jest ona wystarczająca, by w każdym przypadku zapewnić bezpieczeństwo i skuteczność terapii. Konieczne jest zatem edukacja pacjentów poprzez wdrożenie szeroko dyskutowanej obecnie Opieki Farmaceutycznej

Beauty in a tablet - public knowledge about nutraceuticals

SUBJECT OF RESEARCH: Nutricosmetics contain vitamin, mineral and biologically active compounds that have a positive effect on the appearance of the skin, nails and hair. The constantly growing consumption of dietary supplements, including preparations improving the condition of the skin of the hair and nails, promotes the creation of new preparations, but does not increase public awareness of the products used. RESEARCH OBJECTIVE: The aim of the study was to verify patients' knowledge of dietary supplements, with particular emphasis on preparations improving the condition of skin, hair and nails, as well as determining the factors determining the choice of a particular preparation. MATERIALS AND METHODS: The survey was conducted from December 2019 to April 2020 with the participation of a random group of 170 respondents, using the author's anonymous questionnaire containing 33 questions. RESULTS: Based on the results obtained, it can be said that 95% of respondents know the definition of a dietary supplement, but only 46.5% of respondents know that they are intended for healthy people, 54% of respondents declare taking dietary supplements that support the condition of the skin, hair and nails, 1/3 of respondents when choosing a preparation do not pay attention to whether it is a medicine or a dietary supplement, and 40% of respondents are not aware of the differences resulting from the different registration of both preparations. Over 70% of respondents buy dietary supplements at the pharmacy, but only a quarter of respondents use the pharmacist's professional advice. Almost 40% of respondents simultaneously use two or more dietary supplements, without being aware of the possibility of overdose of active substances contained in the preparations taken. Only half of the respondents are satisfied with the effects achieved thanks to the use of dietary supplements that improve the condition of the skin, hair and nails. CONCLUSIONS: Respondents have basic knowledge about dietary supplements used, but constant public education is needed regarding specialist knowledge regarding the quality and method of taking dietary supplements.PRZEDMIOT BADAŃ: Nutrikosmetyki zawierają związki witaminowe, mineralne i biologicznie aktywne, które wpływają korzystnie na wygląd skóry, paznokci i włosów. Stale rosnąca konsumpcja suplementów diety, w tym preparatów poprawiających kondycję skóry włosów i paznokci sprzyja powstawaniu nowych preparatów, jednak nie zwiększa to świadomości społeczeństwa w zakresie stosowanych produktów. CEL BADAŃ: Celem badania była weryfikacja wiedzy pacjentów na temat zażywanych suplementów diety, ze szczególnym uwzględnieniem preparatów poprawiających kondycję skóry, włosów i paznokci, a także określenie czynników, determinujących wybór określonego preparatu. MATERIAŁY I METODY: Badanie prowadzono od grudnia 2019 do kwietnia 2020 roku z udziałem losowej grupy 170 respondentów, za pomocą autorskiego, anonimowego kwestionariusza zawierającego 33 pytania. WYNIKI: Na podstawie uzyskanych wyników można stwierdzić, iż 95% respondentów zna definicję suplementu diety, jednak tylko 46,5% ankietowanych wie, że są one przeznaczone dla osób zdrowych, 1/3 respondentów podczas wyboru preparatu nie zwraca uwagi czy jest on lekiem czy suplementem diety, a 40% badanych nie ma świadomości różnic wynikających z odmiennej rejestracji obu preparatów. Ponad 70% badanych kupuje suplementy diety w aptece, jednak z fachowej porady farmaceuty korzysta jedynie ¼ respondentów. Niemal 40% ankietowanych stosuje jednocześnie dwa lub więcej suplementów diety, nie będąc świadomymi możliwości przedawkowania substancji czynnych zawartych w przyjmowanych preparatach. Jedynie połowa badanych jest zadowolona z efektów osiągniętych dzięki stosowaniu suplementów diety poprawiających kondycję skóry, włosów i paznokci. WNIOSKI: Respondenci posiadają podstawową wiedzę na temat stosowanych suplementów diety, jednak konieczna jest stała edukacja społeczeństwa w zakresie specjalistycznej wiedzy dotyczącej jakości i sposobu przyjmowania suplementów diety

Cellular and Molecular Aspects of Anti-Melanoma Effect of Minocycline—A Study of Cytotoxicity and Apoptosis on Human Melanotic Melanoma Cells

Minocycline is a tetracycline compound with pleiotropic pharmacological properties. In addition to its antibacterial action, it shows many non-antimicrobial effects, including an anti-cancer activity. The anti-cancer action was confirmed in studies on ovarian carcinoma cells, hepatocellular carcinoma cells, glioma cells, or acute myeloid leukemia cells. Malignant melanoma remains a serious medical problem despite the extensive knowledge of the disease. The low effectiveness of the standard treatment, as well as the resistance to therapy, result in high mortality rates. This work aimed to investigate the potential and mechanisms of anti-melanoma action of minocycline. Human skin melanotic melanoma cell line COLO 829 was used in the study. The obtained results showed that minocycline decreased cell viability and inhibited the growth of melanoma cells, proportional to the drug concentration as well as to the time of incubation. The EC50 values were calculated to be 78.6 µM, 31.7 µM, and 13.9 µM for 24 h, 48 h, and 72 h, respectively. It was observed that treated cells had a disturbed cell cycle and significantly changed morphology. Moreover, minocycline caused a decrease in mitochondrial membrane potential and an increase in cells with a low level of reduced thiols. Finally, it was found that the anti-melanoma effect of minocycline was related to the induction of apoptosis. The drug activated caspases 8, 9, and 3/7 as well as increased the number of annexin V-positive cells. The presented results show that minocycline possesses anti-melanoma potential

UVA Radiation Enhances Lomefloxacin-Mediated Cytotoxic, Growth-Inhibitory and Pro-Apoptotic Effect in Human Melanoma Cells through Excessive Reactive Oxygen Species Generation

Melanoma, the most dangerous type of cutaneous neoplasia, contributes to about 75% of all skin cancer-related deaths. Thus, searching for new melanoma treatment options is an important field of study. The current study was designed to assess whether the condition of mild and low-dose UVA radiation augments the lomefloxacin-mediated cytotoxic, growth-inhibitory and pro-apoptotic effect of the drug in melanoma cancer cells through excessive oxidative stress generation. C32 amelanotic and COLO829 melanotic (BRAF-mutant) melanoma cell lines were used as an experimental model system. The combined exposure of cells to both lomefloxacin and UVA irradiation caused higher alterations of redox signalling pathways, as shown by intracellular reactive oxygen species overproduction and endogenous glutathione depletion when compared to non-irradiated but lomefloxacin-treated melanoma cells. The obtained results also showed that lomefloxacin decreased both C32 and COLO829 cells’ viability in a concentration-dependent manner. This effect significantly intensified when melanoma cells were exposed to UVA irradiation and the drug. For melanoma cells exposed to lomefloxacin or lomefloxacin co-treatment with UVA irradiation, the concentrations of the drug that decreased the cells’ viability by 50% (EC50) were found to be 0.97, 0.17, 1.01, 0.18 mM, respectively. Moreover, we found that the redox imbalance, mitochondrial membrane potential breakdown, induction of DNA fragmentation, and changes in the melanoma cells’ cell cycle distribution (including G2/M, S as well as Sub-G1-phase blockade) were lomefloxacin in a dose-dependent manner and were significantly augmented by UVA radiation. This is the first experimental work that assesses the impact of excessive reactive oxygen species generation upon UVA radiation exposure on lomefloxacin-mediated cytotoxic, growth-inhibitory and pro-apoptotic effects towards human melanoma cells, indicating the possibility of the usage of this drug in the photochemotherapy of malignant melanoma as an innovative medical treatment option which could improve the effectiveness of therapy. The obtained results also revealed that the redox imbalance intensification mediated by the phototoxic potential of fluoroquinolones may be considered as a more efficient treatment model of malignant melanoma and may constitute the basis for the development of new compounds with a high ability to excessive oxidative stress generation upon UVA radiation in cancer cells

Molecular and Biochemical Basis of Minocycline-Induced Hyperpigmentation—The Study on Normal Human Melanocytes Exposed to UVA and UVB Radiation

Minocycline is a drug which induces skin hyperpigmentation. Its frequency reaches up to 50% of treated patients. The adverse effect diminishes the great therapeutic potential of minocycline, including antibacterial, neuroprotective, anti-inflammatory and anti-cancer actions. It is supposed that an elevated melanin level and drug accumulation in melanin-containing cells are related to skin hyperpigmentation. This study aimed to evaluate molecular and biochemical mechanism of minocycline-induced hyperpigmentation in human normal melanocytes, as well as the contribution of UV radiation to this side effect. The experiments involved the evaluation of cyto- and phototoxic potential of the drug using cell imaging with light and confocal microscopes as well as biochemical and molecular analysis of melanogenesis. We showed that minocycline induced melanin synthesis in epidermal melanocytes. The action was intensified by UV irradiation, especially with the UVB spectrum. Minocycline stimulated the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) gene. Higher levels of melanin and increased activity of tyrosinase were also observed in treated cells. Moreover, minocycline triggered the supranuclear accumulation of tyrosinase, similar to UV radiation. The decreased level of premelanosome protein PMEL17 observed in all minocycline-treated cultures suggests disorder of the formation, maturation or distribution of melanosomes. The study revealed that minocycline itself was able to enhance melanin synthesis. The action was intensified by irradiation, especially with the UVB spectrum. Demonstrated results confirmed the potential role of melanin and UV radiation minocycline-induced skin hyperpigmentation

Neobavaisoflavone May Modulate the Activity of Topoisomerase Inhibitors towards U-87 MG Cells: An In Vitro Study

Despite many advances in therapy, glioblastoma (GB) is still characterized by its poor prognosis. The main reason for this is unsuccessful treatment, which slightly extends the duration of remission; thus, new regimens are needed. One of many types of chemotherapeutics that are being investigated in this field is topoisomerase inhibitors, mainly in combination therapy with other drugs. On the other hand, the search for new anti-cancer substances continues. Neobavaisoflavone (NBIF) is a natural compound isolated from Psoralea corylifolia L., which possesses anti-oxidant, anti-inflammatory, and anti-cancer properties. The aim of this study was to evaluate the effect of NBIF in human U-87 MG glioblastoma cells in comparison to normal human NHA astrocytes, and to examine if it influences the activity of irinotecan, etoposide, and doxorubicin in this in vitro model. We demonstrated that NBIF decreases U-87 MG cells viability in a dose-dependent manner. Furthermore, we found that it inhibits cell growth and causes glutathione (GSH) depletion more intensely in U-87 MG cells than in astrocytes. This study also provides, for the first time, evidence of the potentialization of the doxorubicin effect by NBIF, which was shown by the reduction in the viability in U-87 MG cells

Nanoparticles Loaded with Docetaxel and Resveratrol as an Advanced Tool for Cancer Therapy

A growing interest in the use of a combination of chemosensitizers and cytostatics for overcoming cancer resistance to treatment and the development of their delivery systems has been observed. Resveratrol (Res) presents antioxidant, anti-inflammatory and chemopreventive properties but also limits multidrug resistance against docetaxel (Dtx), which is one of the main causes of failure in cancer therapy with this drug. However, the use of both drugs presents challenges, including poor bioavailability, the unfavourable pharmacokinetics and chemical instability of Res and the poor water solubility and dose-limiting toxicity of Dtx. In order to overcome these difficulties, attempts have been made to create different forms of delivery for both agents. This review is focused on the latest developments in nanoparticles for the delivery of Dtx, Res and for the combined delivery of those two drugs. The aim of this review was also to summarize the synergistic mechanism of action of Dtx and Res on cancer cells. According to recent reports, Dtx and Res loaded in a nano-delivery system exhibit better efficiency in cancer treatment compared to free drugs. Also, the co-delivery of Dtx and Res in one actively targeted delivery system providing the simultaneous release of both drugs in cancer cells has a chance to fulfil the requirements of effective anticancer therapy and reduce limitations in therapy caused by multidrug resistance (MDR)