Phosphorylation of the tumour suppressor p53 by the CK2/FACT pathway plays a central role in suppressing ultraviolet (UV)-induced skin cancer in animal models. Although p53 protein stabilization is induced after solar-simulated irradiation of human skin in vivo, p53 phosphorylation has not been defined.
To investigate the effects of clinically effective treatments for skin diseases including psoralen + UVA (PUVA) and photodynamic therapy (PDT) on p53 phosphorylation to determine whether the tumour-suppressing p53 kinase pathways are activated upon use of these therapies.
We used antibodies to the ATM/ATR and CK2/FACT phosphorylation sites on p53.
We found that p53 activation was induced selectively by PUVA treatment, while 8-oxo-7,8-dihydroguanine DNA damage was induced selectively by 5-aminolaevulinic acid (ALA)-PDT treatment. Importantly, PUVA treatment resulted in p53 kinase activation, as defined by p53 modification at AT (serine-15) and CK2/FACT (serine-392) sites within the proliferative compartment.
These data demonstrate that PUVA provokes accumulation and phosphorylation of p53 by AT and CK2/FACT within critical proliferative focal points (as determined by p63 colocalization studies) where DNA damage may lead to tumorigenesis. PDT is mechanistically distinct in that there is a lower level of induction of p53 expression with no evidence of AT- or CK2/FACT-mediated phosphorylation. This suggests that the type of DNA damage created by the reactive oxygen species generated by ALA-PDT does not induce the p53 pathway classically required for the repair of DNA photoadducts induced by UV.
"Psoralen promoted osteoblast differentiation by activation of BMP signaling and could be a potential anabolic agent to treat patients with bone loss-associated disease (Tang et al., 2011). Furthermore, psoralen can form DNA interstrand cross-links upon activation with UVA radiation, and the cross-links repair may involve DNA double strand breaks and/or recombination (Finlan et al., 2005; Toyooka and Ibuki, 2009). However, effects of psoralen on anti-multidrug resistance and the molecular mechanisms remain poorly unknown. "
[Show abstract][Hide abstract] ABSTRACT: Chemotherapy is the recommended treatment for advanced-stage cancers. However, the emergence of multidrug resistance (MDR), the ability of cancer cells to become simultaneously resistant to different drugs, limits the efficacy of chemotherapy. Previous studies have shown that herbal medicine or natural food may be feasible for various cancers as potent chemopreventive drug. This study aims to explore the capablility of reversing the multidrug resistance of docetaxel (DOC)-resistant A549 cells (A549/D16) of psoralen and the underlying mechanisms. In this study, results showed that the cell viability of A549/D16 subline is decreased when treated with psoralen plus DOC, while psoralen has no effect on the cell proliferation on A549 and A549/D16 cells. Furthermore, mRNA and proteins levels of ABCB1 were decreased in the presence of psoralen, while decreased ABCB1 activity was also revealed by flow cytometry. Based on these results, we believe that psoralen may be feasible for reversing the multidrug resistance by inhibiting ABCB1 gene and protein expression. Such inhibition will lead to a decrease in ABCB1 activity and anti-cancer drug efflux, which eventually result in drug resistance reversal and therefore, sensitizing drug-resistant cells to death in combination with chemotherapeutic drugs.
Phytomedicine: international journal of phytotherapy and phytopharmacology 06/2014; 21(7). DOI:10.1016/j.phymed.2014.03.008 · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Multicentre randomized controlled studies now demonstrate high efficacy of top- ical photodynamic therapy (PDT) for actinic keratoses, Bowen's disease (BD) and superficial basal cell carcinoma (BCC), and efficacy in thin nodular BCC, while confirming the superiority of cosmetic outcome over standard therapies. Long- term follow-up studies are also now available, indicating that PDT has recurrence rates equivalent to other standard therapies in BD and superficial BCC, but with lower sustained efficacy than surgery in nodular BCC. In contrast, current evi- dence does not support the use of topical PDT for squamous cell carcinoma. PDT can reduce the number of new lesions developing in patients at high risk of skin cancer and may have a role as a preventive therapy. Case reports and small series attest to the potential of PDT in a wide range of inflammatory ⁄infective dermato- ses, although recent studies indicate insufficient evidence to support its use in psoriasis. There is an accumulating evidence base for the use of PDT in acne, while detailed study of an optimized protocol is still required. In addition to high-quality treatment site cosmesis, several studies observe improvements in aspects of photoageing. Management of treatment-related pain ⁄discomfort is a challenge in a minority of patients, and the modality is otherwise well tolerated. Long-term studies provide reassurance over the safety of repeated use of PDT.
[Show abstract][Hide abstract] ABSTRACT: In this paper, analysis and design of a zero voltage switching (ZVS) isolated single-stage charger with interleaved power factor correction (PFC) based on an asymmetrical half- bridge topology is presented. The proposed charger is formed from an interleaved PFC converter and an asymmetrical half-bridge converter. It has the features of constant frequency operation, ZVS and low voltage stress imposed on the active switches. Moreover, it can achieve high power factor, high power density, high efficiency, low switching loss and low component count, which make converter operation at medium power levels feasible. In the paper, theoretical analysis and experimental results of a charger with the proposed topology have verified that power factor (PF) and total harmonics distortion (THD) can be significantly improved. In addition, input current ripple can be also reduced which in turn can reduce the size of line filter. The proposed charger is attractive for electric vehicle (EV) applications.
Telecommunications Energy Conference, 2003. INTELEC '03. The 25th International; 11/2003
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.