Selenate bioreduction in a large in situ field trial.

Removing selenium (Se) from mine effluent is a common challenge. A long-term, in situ experiment was conducted to bioremediate large volumes (up to 7500 mc d-1) of Se(VI)-contaminated water (mean 87 µg L-1) by injecting the water into a saturated waste rock fill (SRF) at a coal mining operation in Elk Valley, British Columbia, Canada. To stimulate/maintain biofilm growth in the SRF, labile organic carbon (methanol) and nutrients were added to the water prior to its injection. A conservative tracer (Br-) was also added to track the migration of injected water across the SRF, identify wells with minimal dilution and used to quantify the extent of bioreduction. The evolution of the Se species through the SRF was monitored in time and space for 201 d. Selenium concentrations of <3.8 µg L-1 were attained in monitoring wells located 38 m from the injection wells after 114 to 141 d of operation. Concentrations of Se species in water samples from complementary long-term (351-498 d) column experiments using influent Se(VI) concentrations of 1.0 mg L-1 were consistent with the results of the in situ experiment. Solid samples collected at the completion of the column experiments confirmed the presence of indigenous Se-reducing bacteria and that the sequestered Se was present as insoluble Se(0), likely in Se-S ring compounds. Based on the success of this ongoing bioremediation experiment, this technology is being applied at other mine sites.

Quantifying denitrification in a field-scale bioremediation experiment.

Nitrate (NO3-) in mine waste rock derived from undetonated NH4NO3 can contaminate receiving waters. An in-situ bioremediation experiment was conducted at a coal mining operation in Elk Valley, British Columbia, Canada to remediate NO3- from large volumes of mine water. Over the test period (201 d), 5000 to 7500 m3 d-1 of NO3--rich (mean concentration 22 mg N L-1) mine water was injected into saturated waste rock along with methanol, nutrients, and a conservative tracer (Br-). Complete denitrification (<0.5 mg N L-1) was recorded in monitoring wells located 38 m from the injection wells after 114 to 141 d of operation. Plots of δ15N- and δ18O-NO3- versus NO3--N concentrations for monitoring wells yielded isotopic enrichment factors (ε) for δ15N- and δ18O-NO3- of -25.7 and -13.2 ‰ for high C/C0 NO3- concentrations (>10.5 mg N L-1) and -5.5 and -3.6 ‰ for lower C/C0 values. The fraction of NO3- denitrified (Dp) calculated using bi-linear ε values for δ15N- and δ18O reproduced the Dp determined independently using a conservative tracer indicating that stable isotope tracers of the NO3- reducing processes in bioremediation are invaluable to determine Dp. Based on the success of this ongoing bioremediation experiment, the technology is being applied at other sites.

Primary feather follicle ablation in common pintails (Anas acuta acuta) and a white-faced whistling duck (Dendrocygna viduata).

Eight 1-yr-old common pintails (Anas acuta acuta) and one 2-yr-old white-faced whistling duck (Dendrocygna viduata) were presented for the persistence of primary flight feathers 1 yr after pinioning. The birds were housed outdoors in an open enclosure necessitating flight prevention. The birds were placed under general anesthesia, and a diode laser was used to ablate the primary feather follicles of the previously pinioned wing. Swelling was the most common side effect seen in seven out of nine treated birds. Other side effects included ulceration, hyperemia, edema, and serosanguinous discharge. All side effects were resolved by 12 wk postprocedure. Laser feather follicle ablation was successful in 28 of 40 (70%) of the treated common pintail feathers, and flight was not observed 7 mo following the procedure in any of these birds. Feather follicle ablation was successful in two of six (33%) of the treated white-faced whistling duck feathers, and the bird in question was observed flying 5 mo after the procedure. Primary feather follicle ablation with a diode laser was a successful method of flight prevention in common pintails but was not effective for a white-faced whistling duck.

Melatonin, a novel Sirt1 inhibitor, imparts antiproliferative effects against prostate cancer in vitro in culture and in vivo in TRAMP model.

We recently demonstrated that Sirt1, a NAD(+) -dependent histone deacetylase, was overexpressed in prostate cancer (PCa) and its inhibition resulted in a significant antiproliferative response in human PCa cells. Studies have suggested a link between Sirt1 and circadian rhythms, the disruption of which has been linked to cancer. Interestingly, a decreased production of the pineal melatonin has been shown to deregulate the circadian rhythm machinery and increase cancer risk. Furthermore, disruption in melatonin production and circadian rhythmicity has been associated with aging. Here, we challenged our hypothesis that melatonin will impart antiproliferative response against PCa via inhibiting Sirt1. We demonstrated that melatonin significantly inhibited Sirt1 protein and activity in vitro in multiple human PCa cell lines, and melatonin-mediated Sirt1 inhibition was accompanied with a significant decrease in the proliferative potential of PCa cells, but not of normal cells. Forced overexpression of Sirt1 partially rescued the PCa cells from melatonin's antiproliferative effects, suggesting that Sirt1 is a direct target of melatonin. Employing transgenic adenocarcinoma of mouse prostate (TRAMP) mice, we also demonstrated that oral administration of melatonin, at human-achievable doses, significantly inhibited PCa tumorigenesis as shown by decreases in (i) prostate and genitourinary weight, (ii) serum insulin-like growth factor-1 (IGF-1)/IGF-binding protein-3 (IGFBP3) ratio, (iii) mRNA and protein levels of the proliferation markers (PCNA, Ki-67). This anti-PCa response was accompanied with a significant decrease in Sirt1 in TRAMP prostate. Our data identified melatonin as a novel inhibitor of Sirt1 and suggest that melatonin can inhibit PCa growth via Sirt1 inhibition.

Antiproliferative effects of apple peel extract against cancer cells.

Studies have shown an inverse relationship between the consumption of apples and the risk of several cancers. The peels of apple, which have been shown to possess exceptionally high concentrations of antioxidants, are often discarded. In this study, we evaluated the antiproliferative effects of apple peel extract (APE) in variety of cancer cell types. Our data demonstrated that APE, obtained from organic Gala apples, imparted significant reduction in the viability of a variety of cancer cell lines. Further, our data showed a significant decrease in growth and clonogenic survival of human prostate carcinoma CWR22Rnu1 and DU145 cells and breast carcinoma Mcf-7 and Mcf-7:Her18 cells. Also, the antiproliferative effects of APE were found to be accompanied by a G0-G1 phase arrest of prostate and breast cancer cells. Furthermore, APE treatment resulted in a marked concentration-dependent decrease in the protein levels of proliferative cell nuclear antigen, a marker for proliferation. In addition, APE treatment resulted in a marked increase in maspin, a tumor suppressor protein that negatively regulates cell invasion, metastasis, and angiogenesis. Our data suggested that APE possesses strong antiproliferative effects against cancer cells, and apple peels should not be discarded from the diet. Detailed mechanistic studies, especially in appropriate in vivo animal models, are needed to further examine the antiproliferative and preventive effects of APE against cancer.

Pharmacokinetics of voriconazole after oral administration of single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis).

OBJECTIVE: To determine the pharmacokinetics and safety of voriconazole administered orally in single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis). ANIMALS: 15 clinically normal adult Hispaniolan Amazon parrots. PROCEDURES: Single doses of voriconazole (12 or 24 mg/kg) were administered orally to 15 and 12 birds, respectively; plasma voriconazole concentrations were determined at intervals via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) or water was administered orally to 6 and 4 birds, respectively, every 8 hours for 11 days (beginning day 0); trough plasma voriconazole concentrations were evaluated on 3 days. Birds were monitored daily, and clinicopathologic variables were evaluated before and after the trial. RESULTS: Voriconazole elimination half-life was short (0.70 to 1.25 hours). In the single-dose experiments, higher drug doses yielded proportional increases in the maximum plasma voriconazole concentration (C(max)) and area under the curve (AUC). In the multiple-dose trial, C(max), AUC, and plasma concentrations at 2 and 4 hours were decreased on day 10, compared with day 0 values; however, there was relatively little change in terminal half-life. With the exception of 1 voriconazole-treated parrot that developed polyuria, adverse effects were not evident. CONCLUSIONS AND CLINICAL RELEVANCE: In Hispaniolan Amazon parrots, oral administration of voriconazole was associated with proportional kinetics following administration of single doses and a decrease in plasma concentration following administration of multiple doses. Oral administration of 18 mg of voriconazole/kg every 8 hours would require adjustment to maintain therapeutic concentrations during long-term treatment. Safety and efficacy of voriconazole treatment in this species require further investigation.

Besnoitia darlingi infection in a Virginia opossum (Didelphis virginiana).

This is a case report of natural infection with Besnoitia darlingi in a Virginia opossum (Didelphis virginiana) in Louisiana. Clinical pathologic data included a severe nonregenerative anemia, inflammatory leukogram, increased hepatocellular leakage enzymes, renal azotemia, hyperkalemia, hypoglycemia, hypoalbuminemia, and proteinuria. Tissue cysts containing bradyzoites were found in the majority of organs, especially the skin, mucous membranes, kidneys, adrenals, lungs, and heart. Images of the bradyzoites obtained by transmission electron microscopy were consistent with the previously described ultrastructure of Besnoitia darlingi. This opossum also suffered from an open phalangeal fracture and concurrent gastrointestinal parasites. Histopathologic findings included a glomerulonephritis and hepatic necrosis.

Spinal lymphoma and pulmonary filariasis in a pet domestic rabbit (Oryctolagus cuniculus domesticus).

Spinal lymphoma and concurrent pulmonary filariasis are reported in a pet rabbit. The rabbit presented for pelvic limb paralysis resulting from extradural spinal lymphoma, presumably rising from the body of the sixth lumbar vertebra. The neoplasm was subsequently immunophenotyped as a B-cell lymphoma. Pulmonary filariasis was an incidental finding at necropsy.

Avian transfusion medicine.

Anemia is defined as a decreased capacity of the blood to carry oxygen and is recognized by packed cell volume, erythrocyte, and hemoglobin values below reference ranges. Causes of anemia in birds include blood loss, heavy metal toxicosis, parasitic infection, and chronic disease. Several differences exist between avian and mammalian physiology, including the avian ability to tolerate greater losses of blood. However, the use of blood products has become an effective tool for treating anemic avian patients. Whole blood transfusions (autologous, homologous, and heterologous) and administration of hemoglobin-based, oxygen-carrying solutions are the treatments used most commonly in birds.

Combination of vitamin E and selenium causes an induction of apoptosis of human prostate cancer cells by enhancing Bax/Bcl-2 ratio.

BACKGROUND: The Selenium and Vitamin E Chemoprevention Trial (SELECT) is aimed at determining the usefulness of a combination of vitamin E and selenium for Prostate cancer (PCa) prevention in humans. The aim of this study is to evaluate the efficacy and mechanistic basis of this combination. METHODS: We determined the effect of vitamin E (+-alpha-tocopheryl succinate, VES) and selenium (methylselenic acid, MSA), alone and in combination, on the proliferation of LNCaP, DU145, and PC-3 cells as well as normal prostate PrEC cells. We also determined the involvement of Bcl-2 family proteins as a mechanism of the biological effects of vitamin E and selenium combination. RESULTS: VES or MSA alone led to a modest inhibition in the viability and growth of PCa cells. However, a combination of these two agents resulted in a dramatic increase in growth inhibition of PCa cells. Interestingly, VES and/or MSA were not found to have any effect on the growth or viability of normal PrEC cells. VES and MSA treatment to human PCa cells resulted in (i) induction of apoptosis, (ii) increase in Bax, Bak, and Bid proteins, and (iii) decrease in Bcl-2 protein. Furthermore, Bax knockdown via shRNA and Bcl-2 overexpression via Bcl-2 plasmid resulted in a rescue of PCa cells from apoptosis. CONCLUSIONS: Our study suggested that vitamin E and selenium combination may be more effective than either of these agents alone. Further, our data demonstrated a causal connection between Bax and Bcl-2 modulation and induction of apoptosis by VES and MSA combination.

Resveratrol imparts photoprotection of normal cells and enhances the efficacy of radiation therapy in cancer cells.

Solar radiation spans a whole range of electromagnetic spectrum including UV radiation, which are potentially harmful to normal cells as well as ionizing radiations which are therapeutically beneficial towards the killing of cancer cells. UV radiation is an established cause of a majority of skin cancers as well as precancerous conditions such as actinic keratosis. However, despite efforts to educate people about the use of sunscreens and protective clothing as preventive strategies, the incidence of skin cancer and other skin-related disorders are on the rise. This has generated an enormous interest towards finding alternative approaches for management of UV-mediated damages. Chemoprevention via nontoxic agents, especially botanical antioxidants, is one such approach that is being considered as a plausible strategy for prevention of photodamages including photocarcinogenesis. In this review, we have discussed the photoprotective effects of resveratrol, an antioxidant found in grapes and red wine, against UVB exposure-mediated damages in vitro and in vivo. In addition, we have also discussed studies showing that resveratrol can act as a sensitizer to enhance the therapeutic effects of ionizing radiation against cancer cells. Based on available literature, we suggest that resveratrol may be useful for (1) prevention of UVB-mediated damages including skin cancer and (2) enhancing the response of radiation therapies against hyperproliferative, precancerous and neoplastic conditions.

Dose translation from animal to human studies revisited.

As new drugs are developed, it is essential to appropriately translate the drug dosage from one animal species to another. A misunderstanding appears to exist regarding the appropriate method for allometric dose translations, especially when starting new animal or clinical studies. The need for education regarding appropriate translation is evident from the media response regarding some recent studies where authors have shown that resveratrol, a compound found in grapes and red wine, improves the health and life span of mice. Immediately after the online publication of these papers, the scientific community and popular press voiced concerns regarding the relevance of the dose of resveratrol used by the authors. The animal dose should not be extrapolated to a human equivalent dose (HED) by a simple conversion based on body weight, as was reported. For the more appropriate conversion of drug doses from animal studies to human studies, we suggest using the body surface area (BSA) normalization method. BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function. We advocate the use of BSA as a factor when converting a dose for translation from animals to humans, especially for phase I and phase II clinical trials.

Role of GLI2 transcription factor in growth and tumorigenicity of prostate cells.

Aberrant activation of the Hedgehog (Hh) signaling pathway has been reported in various cancer types including prostate cancer. The GLI2 transcription factor is a primary mediator of Hh signaling. However, its relative contribution to development of prostate tumors is poorly understood. To establish the role of GLI2 in maintaining the tumorigenic properties of prostate cancer cells, we developed GLI2-specific small hairpin RNA. Knockdown of GLI2 in these cells resulted in significant down-regulation of the Hh signaling pathway, followed by inhibition of colony formation, anchorage-independent growth, and growth of xenografts in vivo. Conversely, ectopic expression of Gli2 in nontumorigenic prostate epithelial cells resulted in accelerated cell cycle progression, especially transition through G(2)-M, and augmented proliferation. Altogether, our findings suggest that GLI2 plays a critical role in the malignant phenotype of prostate cancer cells, and GLI2 may potentially become an attractive therapeutic target for the treatment of prostate cancer.

MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress p53-dependent apoptosis in MAGE-positive cell lines.

The MAGE-A, MAGE-B, and MAGE-C protein families comprise the class-I MAGE/cancer testes antigens, a group of highly homologous proteins whose expression is suppressed in all normal tissues except developing sperm. Aberrant expression of class I MAGE proteins occurs in melanomas and many other malignancies, and MAGE proteins have long been recognized as tumor-specific targets; however, their functions have largely been unknown. Here, we show that suppression of class I MAGE proteins induces apoptosis in the Hs-294T, A375, and S91 MAGE-positive melanoma cell lines and that members of all three families of MAGE class I proteins form complexes with KAP1, a scaffolding protein that is known as a corepressor of p53 expression and function. In addition to inducing apoptosis, MAGE suppression decreases KAP1 complexing with p53, increases immunoreactive and acetylated p53, and activates a p53 responsive reporter gene. Suppression of class I MAGE proteins also induces apoptosis in MAGE-A-positive, p53wt/wt parental HCT 116 colon cancer cells but not in a MAGE-A-positive HCT 116 p53-/- variant, indicating that MAGE suppression of apoptosis requires p53. Finally, treatment with MAGE-specific small interfering RNA suppresses S91 melanoma growth in vivo, in syngenic DBA2 mice. Thus, class I MAGE protein expression may suppress apoptosis by suppressing p53 and may actively contribute to the development of malignancies and by promoting tumor survival. Because the expression of class I MAGE proteins is limited in normal tissues, inhibition of MAGE antigen expression or function represents a novel and specific treatment for melanoma and diverse malignancies.

Protective effect of sanguinarine on ultraviolet B-mediated damages in SKH-1 hairless mouse skin: implications for prevention of skin cancer.

Excessive exposure of solar ultraviolet (UV) radiation, particularly its UVB component (280-320 nm), to human skin is the major cause of skin cancers. UV exposure also leads to the development of precancerous conditions such as actinic keratosis and elicits a variety of other adverse effects such as sunburn, inflammation, hyperplasia, immunosuppression and skin aging. Therefore, there is a need to intensify our efforts towards the development of novel mechanism-based approaches/agents for the protection of UVB-mediated damages. Chemoprevention is being investigated as a potential approach for the management of UV damages including skin cancer. We have earlier shown that sanguinarine, a benzophenanthridine alkaloid, inhibits UVB exposure-mediated damages in HaCaT keratinocytes. In this study, to determine the relevance of our in vitro findings to in vivo situations, we assessed the effects of sanguinarine on UVB-mediated damages in SKH-1 hairless mice. Our data demonstrated that a topical application of sanguinarine (5 micromol 0.3 mL(-1) ethanol per mouse), either as a pretreatment (30 min prior to UVB) or posttreatment (5 min after UVB), resulted in a significant decrease in UVB-mediated increases in skin edema, skin hyperplasia and infiltration of leukocytes. Further, sanguinarine treatments (pre and post) also resulted in a significant decrease in UVB mediated (1) generation of H2O2 and (2) increases in the protein levels of markers of tumor promotion/proliferation viz. ornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA) and Kiel antigen-67. Based on this data, we suggest that sanguinarine could be developed as an agent for the management of conditions elicited by UV exposure including skin cancer. However, further detailed studies are needed to support this suggestion.

The role of Forkhead-box Class O (FoxO) transcription factors in cancer: a target for the management of cancer.

Human Forkhead-Box Class O (FoxO) transcription factors are primarily regulated through the phosphoinositide-3-kinase (PI3k)-Akt pathway via phosphorylation and nuclear exclusion. Acetylation and ubiquitination represent another level of regulation for FoxO proteins and FoxO-regulated gene expression. FoxO factors can act as tumor suppressors; however, the loss of FoxO function leads to increased cellular survival and a predisposition to neoplasia, especially of epithelial cancers. Based on the critical role of FoxO signaling, this family of transcription factors appears to be a promising target for future drug discovery for epithelial cancers. This review describes mechanism of the regulation of FoxO proteins and their role in epithelial cancers. Based on the current knowledge and studies in the past decade, we suggest that the development of novel agents which specifically activate FoxO members could be useful in the prevention as well as treatment of cancer in general and epithelial cancers in particular.

Select cancer testes antigens of the MAGE-A, -B, and -C families are expressed in mast cell lines and promote cell viability in vitro and in vivo.

MAGE antigens are proteins that are normally expressed only in gametes but are often aberrantly expressed in melanomas, hematopoietic malignancies, and other "cancers". The functions of most MAGE proteins are unknown. Data have accumulated suggesting expression of MAGE proteins by malignant cells may contribute to advanced disease or resistance to chemotherapy, but direct evidence supporting this hypothesis is lacking. We show here that small interfering RNA (siRNA) suppression of MAGE-A, -B, and -C gene expression slows proliferation and induces caspase independent apoptosis in human and murine mast cell lines. Furthermore, treatment with MAGE specific siRNA suppresses growth of malignant cells in an in vivo murine model of mastocytosis. These observations demonstrate that MAGE protein expression can contribute to the development of tumors by permitting proliferation and prolonging the survival of malignant cells. We suggest a shift of the current clinical paradigm from one that envisions MAGE proteins solely as targets for immunologic attack to one in which MAGE genes and proteins are also targets for functional manipulation.

Sanguinarine induces apoptosis of human pancreatic carcinoma AsPC-1 and BxPC-3 cells via modulations in Bcl-2 family proteins.

Pancreatic cancer is associated with low responsiveness to conventional chemotherapies and its incidence nearly equals its death rate. This warrants the development of novel mechanism-based approaches for the management of pancreatic cancer. This study was designed to determine the potential of sanguinarine, a plant alkaloid known to possess strong antimicrobial, anti-inflammatory, and antioxidant activities, against human pancreatic carcinoma cells. Employing human pancreatic carcinoma AsPC-1 and BxPC-3 cells, we specifically evaluated the pro-apoptotic and cell cycle deregulatory effects of sanguinarine and evaluated the involvement of Bcl-2 family proteins and p53 as the mechanism of the biological effects of sanguinarine. Our data demonstrated that sanguinarine (at low concentrations of 0.1-10 microM; for 24 h) treatment to AsPC-1 and BxPC-3 cells resulted in a dose dependent (i) inhibition of viability and growth, (ii) colony formation ability, (iii) induction of apoptosis, and (iv) G0-G1 phase cell cycle arrest. Further, sanguinarine-treatment to AsPC-1 and BxPC-3 cells resulted in a dose dependent (i) increase in pro-apoptotic Bax, Bid and Bak proteins; (ii) decrease in anti-apoptotic Bcl-2 and Bcl-X(L) proteins; and (iii) decrease in p53 with an increase in its phosphorylation. Based on our study, we suggest that sanguinarine may be developed as an agent for the management of pancreatic cancer. Indeed, more in depth studies both in vitro as well as in vivo in appropriate relevant animal models are needed to strengthen this suggestion.

S100A4 accelerates tumorigenesis and invasion of human prostate cancer through the transcriptional regulation of matrix metalloproteinase 9.

We previously showed that the calcium-binding protein S100A4 is overexpressed during the progression of prostate cancer (CaP) in humans and in the TRAMP (transgenic adenocarcinoma of the mouse prostate) mouse model. We tested a hypothesis that the S100A4 gene plays a role in the invasiveness of human CaP and may be associated with its metastatic spread. We observed that siRNA-mediated suppression of the S100A4 gene significantly reduced the proliferative and invasive capability of the highly invasive CaP cells PC-3. We evaluated the mechanism through which the S100A4 gene controls invasiveness of cells by using a macroarray containing 96 well characterized metastatic genes. We found that matrix metalloproteinase 9 (MMP-9) and its tissue inhibitor (TIMP-1) were highly responsive to S100A4 gene suppression. Furthermore, S100A4 suppression significantly reduced the expression and proteolytic activity of MMP-9. By employing an MMP-9-promoter reporter, we observed a significant reduction in the transcriptional activation of the MMP-9 gene in S100A4-siRNA-transfected cells. Cells overexpressing the S100A4 gene (when transfected with pcDNA3.1-S100A4 plasmid) also significantly expressed MMP-9 and TIMP-1 genes with increased proteolytic activity of MMP-9 concomitant to increased transcriptional activation of the MMP-9 gene. S100A4-siRNA-transfected cells exhibited a reduced rate of tumor growth under in vivo conditions. Our data demonstrate that the S100A4 gene controls the invasive potential of human CaP cells through regulation of MMP-9 and that this association may contribute to metastasis of CaP cells. We suggest that S100A4 could be used as a biomarker for CaP progression and a novel therapeutic or chemopreventive target for human CaP treatment.

Enhancement of UVB radiation-mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes.

In this article, we studied the chemopreventive effects of sanguinarine on UVB-mediated responses in human HaCaT immortalized keratinocytes. For our studies, HaCaT cells were treated with a low dose (50 nmol/L) of sanguinarine for 24 hours followed by irradiation with UVB (15 or 30 mJ/cm2). Our data showed that UVB exposure, at both doses, resulted in decreased cell viability and increased apoptosis. Interestingly, pretreatment of the cells with sanguinarine caused a significant enhancement in the antiproliferative response of UVB. These responses on UVB and/or sanguinarine treatments were associated with (a) decrease in Bcl-2 and Bcl-X(L) and (b) increase in Bax, Bid, and Bak protein levels. Bax knockdown and Bcl-2 overexpression resulted in a rescue of HaCaT cells from sanguinarine-mediated apoptosis. DNA cell cycle analysis revealed that UVB treatment resulted in an accumulation of cells in the G2-M phase of the cell cycle, whereas pretreatment of sanguinarine resulted in a significant shift of cells in the S phase at a low UVB dose and a further accumulation of cells in the G2-M phase at a higher UVB dose. These effects on cell cycle were accompanied with modulations in the protein levels of cyclin (B1, E, and A) and cdc2 and cyclin-dependent kinase 1. Furthermore, sanguinarine treatment was found to result in significant modulations in p53, p66Shc, MsrA, and superoxide dismutase levels. Based on our data, we suggest the sanguinarine may protect skin cells from UVB-mediated damages via apoptotic elimination of damaged cells that escape programmed cell death and therefore possess a potential of clonal expansion.