Fraxetin Interacts Additively with Cisplatin and Mitoxantrone, Antagonistically with Docetaxel in Various Human Melanoma Cell Lines—An Isobolographic Analysis
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Malignant melanoma is a skin cancer characterized by rapid development, poor prognosis and high mortality. Due to the frequent drug resistance and/or early metastases in melanoma, new therapeutic methods are urgently needed. The study aimed at assessing the cytotoxic and antiproliferative effects of scoparone and fraxetin in vitro, when used alone and in combination with three cytostatics: cisplatin, mitoxantrone, and docetaxel in four human melanoma cell lines. Our experiments showed that scoparone in the concentration range tested up to 200 µM had no significant effect on the viability of human malignant melanoma (therefore, it was not possible to evaluate it in combination with other cytostatics), while fraxetin inhibited cell proliferation with IC50 doses in the range of 32.42–73.16 µM, depending on the cell line. Isobolographic analysis allowed for the assessment of the interactions between the studied compounds. Importantly, fraxetin was not cytotoxic to normal keratinocytes (HaCaT) and melanocytes (HEMa-LP), although it slightly inhibited their viability at high concentrations. The combination of fraxetin with cisplatin and mitoxantrone showed the additive interaction, which seems to be a promising direction in melanoma therapy. Unfortunately, the combination of fraxetin with docetaxel may not be beneficial due to the antagonistic antiproliferative effect of both drugs used in the mixture.Keywords:
Mitoxantrone
HaCaT
Viability assay
The results on the effect of LF from different sources on the viability of two cell lines (Arn8 and HaCaT) are presented in the work. It is shown that both hLF and bLF have an effect on the viability of these two cell lines, and that bLF decreases the cell viability in much more extend than hLF. Possible action mechanisms of LF are discussed.
HaCaT
Viability assay
Lactoferrin
Cell Survival
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The insulin-like growth factor receptor (IGF-IR) is critical in epidermal development and IGF binding protein-3 (IGFBP-3), a modulator of cellular activity with or without IGF-dependence, co-localises with epidermal IGF-IRs. We have investigated whether the greater UV susceptibility of a human keratinocyte cell line (HaCaT) in comparison to normal human keratinocytes (NHKs) may involve differences in the IGF system. At 24 h after UV (960 mJ/cm2 UVB), in comparison to NHKs, HaCaT keratinocytes exhibited significantly higher levels of apoptosis, refractoriness to IGF-I treatment and reduced IGF-IR phosphorylation. Secreted, intact IGFBP-3 (38–42 kDa) and IGFBP-3 mRNA abundance were reduced in HaCaT keratinocytes, but not consistently altered in NHKs. Immunoreactive IGFBP-3 fragments (16–11 kDa) were detected in both UV-exposed cultures. These data suggest that an altered IGF system contributes to HaCaT keratinocyte UV susceptibility and that following UV insult the IGF system may enhance keratinocyte viability and contribute to a return to epidermal homeostasis.
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Human skin
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4713 Background: Two recent phase III trials have shown an improvement in survival with the use of Docetaxel in metastatic androgen-independent prostate cancer (AIPC) compared to mitoxantrone. However no phase II trials have clearly defined the level of activity of docetaxel after mitoxantrone. We sought to define the activity and toxicity of weekly docetaxel as second line chemotherapy after mitoxantrone in men with AIPC. Patients and Methods: 20 men were treated with docetaxel 40mg/m2 weekly for 3 of every 4 weeks until progression or prohibitive toxicity. Endpoints included PSA response, CTC toxicity, time to progression and overall survival. Results: 9 patients (45%) had a 50% or greater reduction in PSA maintained for at least 1 month. Weekly Docetaxel was well tolerated with few major toxicities: 2 patients had Grade 3 diarrhoea (10%), and 6 had grade 2–4 haematologic toxicities (30%). The median time to progression was 5 months (range 0–13) and median survival was 13 months (range 1 to 24) from starting Docetaxel.The median survival from starting mitoxantrone was 19 months Men who had responded to mitoxantrone were no more likely to respond to Docetaxel (p=0.16 Fischer’s exact test) Conclusions: Weekly Docetaxel is a safe and active second line treatment after mitoxantrone for androgen-resistant prostate cancer with similar levels of activity to the first line setting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Eli Lilly Aventis, Eli Lilly
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Cabazitaxel
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Abstract BACKGROUND Docetaxel and mitoxantrone are considered first‐line chemotherapeutic options in patients with hormone‐refractory prostate cancer (HRPC), but their clinical effectiveness in a second‐line setting is unknown. Therefore, the authors conducted a population‐based retrospective study to establish activity and tolerability of second‐line docetaxel or mitoxantrone in HRPC. METHODS The study included 68 patients who had failed androgen ablation therapy and who received docetaxel and mitoxantrone in either sequence. Clinical efficacy in terms of median overall survival (OS), progression‐free survival (PFS), posttreatment prostate‐specific antigen (PSA) decline of ≥ 50% and treatment‐related toxicity were evaluated. RESULTS Of 68 patients, 35 received docetaxel followed by mitoxantrone, and 33 received mitoxantrone followed by docetaxel. Both groups were comparable for recognized pretreatment prognostic factors. Patients who received docetaxel first‐line had a trend toward longer median OS compared with patients treated with second‐line docetaxel after mitoxantrone failure (22 mos, 95% confidence interval [CI], 17.2–26.8 mos vs. 15 mos, 95% CI, 10.4–19.6 mos). Median number of second‐line chemotherapy cycles was 3 and median PFS survival was 2–3 months in both groups. Second‐line docetaxel produced a higher PSA response compared with mitoxantrone (38% vs. 12%, P = 0.012), but this did not translate to a survival benefit. Both second‐line docetaxel and mitoxantrone were associated with a high frequency of treatment‐related adverse events that resulted in dose reduction, delay, or discontinuation (64% and 46% of patients, respectively). CONCLUSIONS Study results favored docetaxel given up‐front for patients with HRPC considered suitable for further chemotherapy. Second‐line docetaxel or mitoxantrone had limited efficacy and tolerability. Patients who are candidates for second‐line chemotherapy, should be enrolled into clinical trials. Cancer 2006. © 2006 American Cancer Society.
Mitoxantrone
Refractory (planetary science)
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Objectives: This study was performed to assess the protective effect of Saengmaek-san (SM) on UVB-induced HaCaT cell damage. Methods: The protective effects of Saengmaek-san(SM) were determined by UVB-induced HaCaT assay. We assessed protective effects of Saengmaek-san (SM) on LDH release and nitrite release from HaCaT. And COX-2, Bcl-2, Bax, , c-jun, c-fos, NF-kB, iNOS, Bcl-xL gene expression were determined in HaCaT using real-time PCR method. Results: 1. SM inhibited LDH-release, nitrite production in UVB-exposed HaCaT. 2. SM suppressed the gene expression of COX-2, in UVB-exposed HaCaT. 3. SM increased the gene expression of Bcl-2, Bax, Bcl-xL family protein in UVB-exposed HaCaT. 4. SM suppressed the gene expression of c-jun, c-fos, NF-kB in UVB-exposed HaCaT. Conclusions: The study showed SM inhibited the cell damage in UVB-exposed HaCaT.
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Cell damage
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In this study,MTT assay was carried out to study the effect of different extracts from Anti-UV Clone(Obtained from Bupleurum scorzonerifolium Willd.callus) on the viability of human keratinocyte cells(HaCaT cells) exposure to UV-B radiation.The results showed that both ethanol and ethyl acetates extract of the cell clone inhibited the viability of HaCaT cells.However the viability of HaCaT cells was promoted by the water extract of the cell clone in a dose dependent manner,thus the water extract was chose to further assay.At a dose range of 0.05—0.2U/mL,pre-treatments and post-treatment with water extract both improved the viability of HaCaT cells compared to cells only exposed to UV-B irradiation(p0.05).When at a concentration of 0.2U/mL,pre-treatments and post-treatment with water extract can improve the cell viability by 10.54% and 14.95% respectively in respect to cells only exposed to UV-B irradiation.Thus it was concluded that the water extract of Anti-UV Clone probably contains UV-B protection agents.
HaCaT
Viability assay
clone (Java method)
MTT assay
Cell Survival
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Mitoxantrone
Crossover study
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Opuntia milpa alta polysaccharides (ODP) are bioactive compounds extracted from Opuntia milpa alta and widely used in the treatment of diseases, but the therapeutic mechanism of ODP on inflammatory injury remains unclear. Therefore, this study explores the effects and mechanisms of ODP in lipopolysaccharide (LPS)-induced inflammation of human keratinocytes (HaCaT). In this experiment, ODP was extracted via the water extraction and fermentation methods, respectively. LPS was then used to induce inflammatory damage in HaCaT cells, and the stimulated cells were treated with different concentrations of ODP. Cell viability was detected by MTT assay, and the concentrations of COX-2, iNOS, IL-6, IL-8, IL-10 and TNF-α were determined by enzyme-linked immunosorbent assay (ELISA). Changes in inflammatory cytokines and related mRNA expression were observed to assess LPS-induced cell damage. In the experiment, it was found that the LPS stimulation of HaCaT cells can induce cellular inflammatory response, reduce cell viability, increase cell apoptosis and increase the expression of COX-2, iNOS, IL-6, IL-8, IL-10 and TNF-α. However, the experimental data shows that ODP can reverse the above results by increasing cell viability, inhibiting cell apoptosis, reducing the expression of the above genes and inactivating antioxidant pathways, which revealed the specific mechanism of ODP repairing LPS-induced inflammatory damage to Hacat cell. In addition, The experimental results showed that fermentation could improve the anti-inflammatory effect of ODP. In conclusion, our experimental results indicate that ODP fermented by lactic acid bacteria can be used as an anti-inflammatory agent.
HaCaT
Viability assay
MTT assay
Proinflammatory cytokine
Cell damage
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Phellinus igniarius is widely used for anti-oxidation in China, and the effect of anti-oxidation of polysaccharides from Phellinus igniarius fruiting body (PIP) was studied in this article. AFM was used to scan the different groups of HaCaT cells. The HaCaT cells height, adhesion and Young's modulus were determined. In this study, the height of HaCaT cells were close gradually to the normal HaCaT cells after ethanol induced oxidative damage when cultured with PIP for 6-24 h, and the results were time-dependent. The adhesion of HaCaT cells cultred with PIP for 18h was closer to the normal cells than that with PIP for 12h. When the cells cultured with the PIP for 12-24 h, the HaCaT cells Young's modulus with ethanol induced oxidative damage was close to that of normal HaCaT cells. These results demonstrated that the effect of PIP against oxidative damage of HaCaT cells.
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Mitoxantrone
Estramustine
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