Effect of Caffeine on UVB‐induced Carcinogenesis, Apoptosis, and the Elimination of UVB‐induced Patches of p53 Mutant Epidermal Cells in SKH‐1 Mice<sup>†</sup>

Conney, Allan H.; Kramata, Pavel; Lou, You-Rong; Lu, Yao-Ping

doi:10.1111/j.1751-1097.2007.00263.x

Cited by 28 publications

(21 citation statements)

References 29 publications

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“…If the DNA damage is not repaired or the damaged cells are not eliminated by apoptosis, the consequences can be cell transformation, uncontrolled proliferation, and eventually skin Family history of melanoma, % 3 tumor formation (29). Mouse studies have shown that oral or topical caffeine administration promotes elimination of UVdamaged keratinocytes (the cells from which nonmelanoma skin cancer arises) via apoptosis and markedly reduces the risk of subsequent skin cancer development (8,(30)(31)(32). The mechanisms and molecular targets for the proapoptotic effect of caffeine after DNA damage have been investigated in cultured cell lines (human osteosarcoma cells).…”

Section: Discussionmentioning

confidence: 99%

Increased Caffeine Intake Is Associated with Reduced Risk of Basal Cell Carcinoma of the Skin

Song

Qureshi²,

Han³

2012

Cancer Research

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Studies in animals suggest that caffeine administration helps prevent squamous cell skin cancer development, but there have been limited epidemiologic studies on the association between caffeine consumption and skin cancer risk. Using data from the Nurses' Health Study and the Health Professionals Follow-up Study, we prospectively examined risks of basal cell carcinoma (BCC, 22,786 cases), squamous cell carcinoma (SCC, 1,953 cases), and melanoma (741 cases) in relation to caffeine intake. Cox proportional hazard models were used to calculate relative risks (RR) and 95% confidence intervals (CI). The amount of caffeine intake from all dietary sources was inversely associated with BCC risk. Compared with the lowest quintile, the highest quintile had the lowest risk (RR, 0.82 in women; 95% CI:,0.77-0.86 and RR, 0.87 in men; 95% CI, 0.81-0.94; P trend < 0.0001 in both). A significant inverse association was also found between caffeinated coffee consumption and BCC risk. Compared with individuals who consumed caffeinated coffee less than 1 cup per month, women who consumed more than 3 cups/d had the lowest risk (RR, 0.79; 95% CI, 0.74-0.85; P trend < 0.0001) and the RR for men was 0.90 (95% CI, 0.80-1.01; P trend ¼ 0.003). Caffeine from other dietary sources (tea, cola, and chocolate) was also inversely associated with BCC risk. Decaffeinated coffee consumption was not associated with a similar decrease in BCC risk. In contrast, caffeine intake was not found to be inversely associated with risks of SCC or melanoma. Our findings argue that caffeine intake in men and women is inversely associated with risk of BCC. Cancer Res; 72(13); 3282-9. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 99%

Increased Caffeine Intake Is Associated with Reduced Risk of Basal Cell Carcinoma of the Skin

Song

Qureshi²,

Han³

2012

Cancer Research

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“…A aplicação tópica de cafeína em ratos após submissão à irradiação UV indica que essa substância também é capaz de diminuir o dano ao DNA, a lesão de queratinócitos e a fotocarcinogênese (Koo et al, 2007;Cooney et al, 2008;Lou et al, 2010;Szeto e Tong, 2010).…”

Section: Introductionunclassified

Efeitos da ingestão de cafeína durante a gestação e a lactação sobre a pele de ratas e de filhotes e sua relação com as concentrações séricas do cortisol materno

Botelho

Reis

Ocarino

et al. 2015

Arq. Bras. Med. Vet. Zootec.

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Efeitos da ingestão de cafeína durante a gestação e a lactação sobre a pele de ratas e de filhotes e sua relação com as concentrações séricas do cortisol materno RESUMOO objetivo deste trabalho foi verificar os efeitos da ingestão materna de diferentes doses de cafeína durante a gestação e a lactação, na pele de ratas-mães e filhotes, bem como sua relação com as concentrações séricas do cortisol materno. Vinte e quatro ratas Wistar adultas foram distribuídas em quatro grupos, representados pelo controle e tratados, com cafeína nas doses de 25, 50 e 100mg/kg. Os grupos tratados receberam cafeína por sonda orogástrica durante toda a gestação e a lactação. O controle recebeu água destilada como placebo. Foram avaliados e quantificados os diferentes tipos de folículos pilosos e a espessura da epiderme. A técnica de imuno-histoquímica, com o uso do anticorpo anti-CDC47, foi utilizada para avaliar a proliferação celular da epiderme e dos folículos pilosos das mães. Na mãe, também foram mensurados os níveis séricos de cortisol pela técnica da quimioluminescência. Os dados foram submetidos à análise de variância com comparação das médias pelos testes Kruskal-Wallis e SNK. Nos grupos tratados com cafeína nas doses de 25 e 50mg/kg, tanto as mães quanto seus filhotes apresentaram hipotricose e/ou alopecia focal. Apesar de a frequência de alterações macroscópicas das mães ter sido superior a dos filhotes, nestes as lesões, quando presentes, foram difusas. A análise histológica demonstrou calcinose de folículos pilosos nas mães e nos filhotes. Mas a morfometria somente revelou diferença significativa no número de folículos pilosos das mães, bem como redução significativa da proliferação celular dos folículos pilosos do grupo tratado com 50mg/kg de cafeína. Os níveis de cortisol materno somente foram significativamente elevados no grupo tratado com 100mg/kg de cafeína. Conclui-se que a cafeína ingerida pelas ratas gestantes e lactantes pode causar lesões cutâneas tanto nas mães quanto nos filhotes, caracterizadas por hipotricose e/ou alopecia, independentemente dos níveis séricos do cortisol materno.Palavras-chave: rata, cafeína, pele, alopecia, cortisol ABSTRACT

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“…We have previously shown that the mTOR/PI3K inhibitor, BGT226, is able to reduce tumour growth rates in mice transplanted with SCC cells (19). In the present study, mice were injected with SCC25 cells and when the tumours were between 4 to 5 mm in diameter we treated them with i) vehicle, ii) 0.5 mg/kg doxorubicin i.p.…”

Section: The Sphk1 Specific Inhibitor Sk1-i (Bml-ei411) Sensitises mentioning

confidence: 99%

“…UV can also activate CD95 death receptor signaling pathways independent of its natural ligand CD95L [17]. The subsequent formation of a death-inducing signaling complex (DISC) is characteristic of death receptor-mediated apoptosis in response to UV radiation [18,19]. Activation of death receptor signaling ultimately activates the initiator pro-caspases-8/-10 leading to the eventual activation of downstream effector procaspases -3,-6,-7 [12].…”

Section: Sunburn Cells (Uv-induced Cell Death)mentioning

confidence: 99%

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The role of E2F7 and E2F8 in squamous differentiation, UV- and chemotherapy-induced responses in keratinocytes

Rethinam¹

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Among keratinocyte-derived squamous cell carcinoma (SCC), cutaneous SCC (CSCC) is the second most common cutaneous cancer type and the most common of the potentially fatal skin cancers. Approximately 90% of head and neck cancers are SCC (HNSCC) and HNSCC worldwide is the sixth most common cancer type afflicting mankind. While resectable disease may be treated by surgery with radiation or chemoradiation, there are still no curative options for advanced, unresectable disease. However, chemotherapy alone may offer a hope for unresectable, disseminated SCC, where 50-60% of patients have disease recurrence within 2 years and approximately 30% of these develop metastatic disease. The mainstay of chemotherapeutic treatment in SCC is the platinum-based drug, cisplatin, 5-fluorouracil (5-FU), taxanes, and anti-EGFR monoclonal antibody such as Cetuximab. Nonetheless, despite advances in treatment techniques, the 5-year survival rate still remains at around 55%.Therefore, there remains a lack of options for recurrent or metastatic disease.The E2F family of transcription factors has emerged as key regulators of proliferation, differentiation and response to stress and apoptotic stimuli in keratinocytes. Consistent with these roles, dysregulation of E2F expression/activity is a common occurrence in cancer and SCC in particular. Thus, better understanding of the E2F family of proteins is essential to establish how these processes are disrupted during SCC genesis. The E2F network exists as a complex map of interacting pathways, and the complete understanding of the E2F family will not be possible until physiological functions of newly identified inhibitory E2F proteins, E2F7 and E2F8, are fully revealed. I provide strong evidence, from in vitro experiments, that E2F7 plays a unique and non-redundant role in modulating UV-or chemotherapy-induced cytotoxicity whereas E2F8 has a unique and non-redundant capacity to regulate squamous differentiation. In addition, I report on a unique feedback loop between E2F1, E2F7 and E2F8 that highlights a previously unreported interdependent axis.With respect to E2F7-specific functions, my work characterised two previously unidentified pathways as therapeutic targets, E2F7/Sphk1/S1P/AKT and E2F7/RacGAP1/AKT, by which the transcription factor E2F7 suppresses doxorubicin specific sensitivity in SCC cells.Targeting these pathways has the potential to expand the clinical activity of existing chemotherapeutics. I provide, in vitro, in vivo and patient data in this study that shows that E2F7-dependent repression of doxorubicin sensitivity is mediated via the induction of Sphingosine kinase 1 (Sphk1) and Rac GTPase activating protein 1 (RacGAP1). These are iii both novel findings and have significant implications for drug resistant SCC. Specifically, Ishowed that (i) E2F7 is overexpressed in patient SCCs and inhibits sensitivity to doxorubicin, (ii) that E2F7-dependent doxorubicin resistance is mediated via E2F-dependent induction of Sphk1 leading to overproduction of Sphingosine-1-phosphate ...

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Effect of Caffeine on UVB‐induced Carcinogenesis, Apoptosis, and the Elimination of UVB‐induced Patches of p53 Mutant Epidermal Cells in SKH‐1 Mice^†

Cited by 28 publications

References 29 publications

Increased Caffeine Intake Is Associated with Reduced Risk of Basal Cell Carcinoma of the Skin

Increased Caffeine Intake Is Associated with Reduced Risk of Basal Cell Carcinoma of the Skin

Efeitos da ingestão de cafeína durante a gestação e a lactação sobre a pele de ratas e de filhotes e sua relação com as concentrações séricas do cortisol materno

The role of E2F7 and E2F8 in squamous differentiation, UV- and chemotherapy-induced responses in keratinocytes

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Effect of Caffeine on UVB‐induced Carcinogenesis, Apoptosis, and the Elimination of UVB‐induced Patches of p53 Mutant Epidermal Cells in SKH‐1 Mice†

Cited by 28 publications

References 29 publications

Increased Caffeine Intake Is Associated with Reduced Risk of Basal Cell Carcinoma of the Skin

Increased Caffeine Intake Is Associated with Reduced Risk of Basal Cell Carcinoma of the Skin

Efeitos da ingestão de cafeína durante a gestação e a lactação sobre a pele de ratas e de filhotes e sua relação com as concentrações séricas do cortisol materno

The role of E2F7 and E2F8 in squamous differentiation, UV- and chemotherapy-induced responses in keratinocytes

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Effect of Caffeine on UVB‐induced Carcinogenesis, Apoptosis, and the Elimination of UVB‐induced Patches of p53 Mutant Epidermal Cells in SKH‐1 Mice^†