In vitro anti-proliferative effect and in vivo antitumor action of daphnetin in different tumor cells.

ANTECEDENTES: Los efectos antiinflamatorios de la dafnetina (7,8-dihidroxicumarina) han sido bien documentados, pero su potencial como agente anticanceroso es controversial y no se ha explorado suficientemente. MATERIAL Y MÉTODOS: En este trabajo se evalúa el efecto antiproliferativo in vitro de la dafnetina en tres líneas celulares mediante ensayos de MTT, así como su efecto antitumoral in vivo en cuatro diferentes tipos de tumores en ratones. RESULTADOS: Con una correlación entre los resultados in vitro e in vivo, los tipos de células probadas tienen diferente sensibilidad al compuesto. Las siguientes líneas celulares están ordenadas de acuerdo con la potencia antiproliferativa in vitro de la dafnetina: células de melanoma B16 (IC50 = 54 ± 2.8 µM) > células de adenocarcinoma de mama MXT (IC50 = 74 ± 6.4 µM) > células de carcinoma de colon C26 (IC50 = 108 ± 7.3 µM). In vivo, la dosis antitumoral óptima de dafnetina fue de 40 mg/kg, y las magnitudes de inhibición fueron las siguientes: tumor B16 (48%) > tumor MXT (40%) > tumor fibrosarcoma S180 (30%) > tumor C26 (20%). CONCLUSIÓN: Los resultados indican que la dafnetina podría tener un impacto como adyuvante para mejorar la efectividad de la quimioterapia convencional.

BACKGROUND: The anti-inflammatory effects of daphnetin (7,8-dihidroxicoumarin) have been well-documented, but the potential of daphnetin as an anticancer agent is controversial and remains insufficiently explored. MATERIAL AND METHODS: In this work, we evaluated the in vitro anti-proliferative effect of daphnetin in three cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, as well as its in vivo antitumor effect in four different types of mouse tumor. RESULTS: With a correlation between in vitro and in vivo results, the tested cell types have different sensitivity to the compound. The following cell lines are arranged according to the in vitro anti-proliferative potency of daphnetin: B16 melanoma cells (inhibitory concentrations 50 [IC50] = 54 ± 2.8 µM) > mitoxantrone (MXT) breast adenocarcinoma cells (IC50 = 74 ± 6.4 µM) > C26 colon carcinoma cells (IC50 = 108 ± 7.3 µM). In vivo, the optimal antitumor dose of daphnetin was 40 mg/kg and the magnitudes of inhibition were the following: B16 tumor (48%) > MXT tumor (40%) > S180 fibrosarcoma tumor (30%) > C26 tumor (20%). CONCLUSION: Our results indicate that daphnetin might have an impact as adjuvant to improve the effectiveness of conventional chemotherapy.

Combination of pentoxifylline and α-galactosylceramide with radiotherapy promotes necro-apoptosis and leukocyte infiltration and reduces the mitosis rate in murine melanoma.

Despite the success for the treatment of melanoma such as targeted molecular therapy, the use of such treatments are expensive For this reason, this study was carried out to explore the anti-cancer properties of available drugs that are able to modify the melanoma prognosis. The study was conducted in two phases: Evaluation of pharmacological effects of pentoxifylline (PTX) administered above (60 mg/kg) which is the therapeutic dose that is aimed at reducing the side-effect of radiotherapy, and of α- galactosylceramide (GalCer) administered at 100 µg/kg, as well as their combination using a murine model (BDF1 mice) of melanoma cell line (B16-F1, ATCC). For the radiotherapy phase, 9 Gy was applied in the tumor area, before (3 days), during (30 min) and after (3 days) the PTX + GalCer treatment. In both study phases, the mitosis rate, leukocyte infiltration and necro-apoptosis were assessed using histological and immunohistochemical approach and tumor volume evaluation as biomarkers. All treatments showed good prognosis results estimated as reduction of mitosis rate (PTX + GalCer after radiotherapy and GalCer), increased leukocyte infiltrate (PTX + GalCer after radiotherapy and GalCer) and necro-apoptosis augmentation (PTX + GalCer after radiotherapy and radiotherapy control). Nevertheless, a lower development of tumor volume was found in GalCer treatment. In this way, it is possible to suggest that the integrated treatment with immuno-stimulators such as GalCer, plus drug used for peripheral vascular disease (PTX) after radiotherapy is probably an alternative for controlling aggressive melanoma in murine model.