Caffeine improves the cytotoxic effect of dacarbazine on B16F10 murine melanoma cells.

OBJECTIVE: Caffeine has been studied as a potentiating agent in chemotherapy against some types of cancer, but there are few reports on its effects on melanoma. This study aimed to investigate caffeine's ability to enhance the effects of dacarbazine in vitro. MATERIALS AND METHODS: Murine melanoma B16F10 cells were treated 24 h with 1-40 µM caffeine. We evaluated cytotoxicity, DNA damage, apoptosis, and oxidative lesion induced by dacarbazine associated with caffeine. The metabolization of these drugs, as well as immunocytochemical labeling, were also evaluated. CONCLUSIONS: The pre-treatment with caffeine showed to be more effective. Caffeine potentiated dacarbazine-induced cytotoxic effects by increasing dacarbazine biotransformation, apoptosis, DNA damage, and malondialdehyde levels; also, caffeine reduced Ki67 and ERK1/2 nuclear labeling and increased p53 labeling in B16F10 cells. In our experiment, caffeine promoted modifications associated with dacarbazine metabolism by viable cells potentiating this antineoplastic drug. These promising results should be further evaluated in experimental models in vivo.

Protective effect of metformin in an aberrant crypt foci model induced by 1,2-dimethylhydrazine: Modulation of oxidative stress and inflammatory process.

Colorectal Cancer (CRC) is the third most frequent type of cancer worldwide. In the past few years, studies have revealed a protective effect of metformin (MET-an anti-hyperglycemic drug, used to treat type 2 diabetes), against CRC. The protective effect of MET has been associated with AMPK activation (and mTOR inhibition), resulting in suppressed protein synthesis, and reduced cell proliferation in malignant transformed cells. To elucidate new mechanisms for the protective effect of metformin, we evaluated the oxidative stress and inflammatory process modulation, since these processes are strictly involved in colorectal carcinogenesis. The present study evaluated the protective effect of MET in a CRC model induced by 1,2-dimethylhydrazine (DMH) in Balb/c female mice. The simultaneous/continuous treatment (administration of MET and DMH simultaneously), revealed protective activity of MET, preventing the formation of aberrant crypt foci (ACF) in 71.4% at distal colon sections, and was able to restore basal labeling of apoptosis. Treatment with MET also reduced the inflammatory process induced by DMH, resulting in of the reduction of oxidative stress and nitric oxide related parameters. © 2016 Wiley Periodicals, Inc.

Citral prevents UVB-induced skin carcinogenesis in hairless mice.

The incidence of skin cancers has increased worldwide, requiring more prevention of this type of cancer. The use of sunscreen and the control of the time of exposure to sunlight are the recognized forms of prevention. However, new substances have been researched in order to develop formulations with more efficient protective activity. Citral is a natural compound with lemon scent that is used in food and cosmetic industries. The present work evaluated the chemoprotective effect of citral during UVB-induced skin carcinogenesis. Male hairless mice HRS/J, 8-12 weeks old, were exposed to UVB irradiation for 24 weeks, with a cumulative radiation dose of 13.875 J/cm2. Citral (0.1, 0.5 and 1%) was applied to the skin at a dosage of 0.1 g/animal, 5 min after UVB exposure. At the end of the experiment, the number of lesion/animal, and size of lesions were measured. The histological sections of the skin were evaluated for the presence and intensity of actinic keratosis and squamous cell carcinoma. TUNEL assay was performed for apoptosis evaluation. Skin samples were used for the measurement of oxidative stress parameters (total radical-trapping antioxidant parameter of skin, glutathione, catalase activity and malondialdehyde), and cytokines levels (IL-1ß, IL-4, IL-10, IL-23, TNF-α, and IFNγ). Citral 1% completely inhibited UVB-induced skin carcinogenesis by reducing levels of oxidative stress and pro-inflammatory cytokines, increasing apoptotic rate in the skin.

Looking beyond the skin: Cutaneous and systemic oxidative stress in UVB-induced squamous cell carcinoma in hairless mice.

Cumulative ultraviolet (UV) exposure is associated with squamous skin cell carcinoma. UV radiation induces oxidative modifications in biomolecules of the skin leading to photocarcinogenesis. Indeed, the cyclobutene pyrimidine dimers and other dimers formed by photoaddition between carbon-carbon bonds also have an important role in the initiation process. However, information on the systemic redox status during these processes is scarce. Thus, we investigated the systemic redox profile in UVB-induced squamous cell carcinoma in mice. Female hairless mice were exposed to UVB radiation (cumulative dose = 17.1 J/cm2). The dorsal skin of these mice developed actinic keratosis (AK) and squamous cell carcinoma (SCC) and presented increased levels of oxidative and nitrosative stress biomarkers (4-hydroxy-2-nonenal and 3-nitrotyrosine), and decreased antioxidant defenses. Systemically, we observed the consumption of plasmatic antioxidant defenses and increased levels of advanced oxidized protein products (AOPP), an oxidative stress product derived from systemic inflammatory response. Taken together, our results indicate that UVB chronic irradiation leads not only to adjacent and tumoral oxidative stress in the skin, but it systemically is reflected through the blood. These new findings clarify some aspects of the pathogenesis of SCC and should assist in formulating better chemoprevention strategies, while avoiding additional primary SCC development and metastasis.