海发菜提取物脱镁叶绿素酸盐A对六种癌细胞的光毒性

目的 探讨脱镁叶绿素酸盐A（PPBa）的体外光动力抗肿瘤活性及化学特性。方法 将乳腺癌细胞（MCF-7）、肺癌细胞（A549）、宫颈癌细胞（HeLa）和3种肝癌细胞（HepG2、hep3B、sk-Hep1）接种于96孔板中,MTT法观察PPBa的光毒性和暗毒性大小,光照强度和药物浓度对PPBa光毒性的影响,Hoechst染色在共聚焦显微镜观察PPBa的摄取,活性氧检测试剂盒通过流式检测和共聚焦显微镜下观察单线态氧的产生,根据PPBa自身的发光特性通过酶标仪测吸光度观察PPBa的光漂性。结果 PPBa对6种癌细胞都有极强的光毒性和极低的暗毒性,PPBa的主要摄取部位是细胞质,单线态氧的产生与给药浓度具有强依赖性,光漂性极低。结论 脱镁叶绿素酸盐A对乳腺癌细胞（MCF-7）的光毒性最强,各种性质优良,具有理想的光敏剂特性。     

The effect of vitamin a on the uptake of a water soluble and lipid soluble nitrosourea by the EMT6 mouse mammary tumor.

Recent reports have suggested that vitamin A, a recognized membrane-active agent, enhances the antitumor effect of certain lipid nitrosoureas in marine L1210 leukemia, when used as a pretreatment agent. A possible explanation may involve enhanced uptake or binding of the alkylating nitrosourea. This theory was tested by administering the lipid soluble ¹⁴C-CCNU and water soluble ¹⁴C-chlorozotocin (CZL), following vitamin A pretreatment (200 mg/kg), to mice bearing a solid tumor (EMT6 Mouse Mammary Tumor), and following the levels of radioactivity in the tumor versus time. A comparison of vitamin A pretreated mice with non-pretreated mice showed vitamin A to have no significant effect upon the incorporation of CLZ, and no enhancement of its antitumor activity, as measured by monitoring growth. On the other hand, the incorporation of the highly lipid soluble CCNU was significantly reduced by vitamin A pretreatment. CCNU, with or without vitamin A pretreatment, had little effect upon the growth of the tumor, while CLZ showed significant reduction in tumor size and growth. It appears that any enhancement of the antitumor activity of nitrosoureas by vitamin A does not involve increased uptake or prolonged binding of the alkylating agent.     

Retinoids as anti-cancer agents and their mechanisms of action

Retinoids (vitamin A) have been reported extensively for anti-cancer properties due to their high receptor-binding affinities and gene regulation abilities. However, the anti-cancer potential of retinoids has not been reviewed in recent years. Thus, this review focused on the anti-cancer effects of retinoids and their synergistic effects with other drugs, together with their mechanisms of action in different types of cancers reported in the past five years. The retinoids were well studied in breast cancer, melanoma, and colorectal cancer. Synthetic retinoids have shown higher selectivity, stronger effectiveness, and lower toxicity than endogenous retinoids. Interestingly, the combination treatment of endogenous retinoids with chemotherapy drugs showed enhanced anti-cancer effects. The mechanisms of action reported for retinoids mainly involved the RAR/RXR signaling pathway. However, limited clinical studies were conducted in recent years. Thus, retinoids which are highly potential anti-cancer agents are worth further study in clinical, especially as a combination therapy with chemotherapy drugs.     

常见肿瘤患者血清维生素A,E,C水平

本文报告２６０例恶性肿瘤患者血清维生素Ａ、Ｅ、Ｃ水平的测定结果。发现除慢性白血病外，蓁７种恶性肿瘤患者血清维生素Ａ水平平均显著低于健康人（Ｐ＜０．０１）；急性白血，肝癌、食管癌患者血清维生素Ｅ水平显著低于健康人（Ｐ＜０．０５）；急性粒细胞白血病、急性单核细胞白血病、肝癌患者血维生素Ｃ水平显著低于健康人（Ｐ＜０．０１）。本研究工作为维生素Ａ、Ｅ、Ｃ药物在肿瘤临床上的应用提供了参考。     

Retinoids in the prevention of bladder cancer

Superficial bladder cancer has an unpredictable natural history but in many patients it has a tendency for multiple recurrences over many years. Chemoprevention approaches are ideally tested in this type of tumor and may delay or prevent recurrences of superficial bladder cancer or prevent progression to invasive disease. Vitamin A and its derivatives, the retinoids, have been studied in detail in this disease. This article reviews the data on this subject and includes in vitro and in vivo preclinical studies as well as the clinical studies performed in the secondary prevention of this disease.     

Retinoids induced astrocytic differentiation with down regulation of telomerase activity and enhanced sensitivity to taxol for apoptosis in human glioblastoma T98G and U87MG cells

We hypothesized that induction of differentiation with retinoid could increase sensitivity to microtubule-binding drug taxol (TXL) for apoptosis in human glioblastoma T98G and U87MG cells. Treatment of cells with 1 μM all-trans retinoic acid (ATRA) or 1 μM 13-cis retinoic acid (13-CRA) for 7 days induced astrocytic differentiation, overexpression of glial fibrillary acidic protein (GFAP), and also down regulated telomerase expression and activity, thereby increased sensitivity to TXL for apoptosis. Treatment of glioblastoma cells with TXL triggered production of reactive oxygen species (ROS), induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), and activated the redox-sensitive c-Jun NH₂-terminal kinase 1 (JNK1) pathway. Moreover, TXL activated Raf-1 kinase for phosphorylation and inactivaion of anti-apoptotic Bcl-2 protein. The events of apoptosis included increase in expression of Bax, down regulation of Bcl-2 and baculoviral inhibitor-of-apoptosis protein (IAP) repeat containing (BIRC) proteins, mitochondrial release of cytochrome c and Smac into the cytosol, increase in intracellular free [Ca²⁺], and activation of calpain, caspase-9, and caspase-3. Increased activity of caspase-3 cleaved inhibitor of caspase-activated DNase (ICAD) to release and translocate CAD to the nucleus for DNA fragmentation. Involvement of stress signaling kinases and proteolytic activities of calpain and caspase-3 in apoptosis was confirmed by pretreating cells with specific inhibitors. Taken together, our results suggested that retinoid (ATRA or 13-CRA) induced astrocytic differentiation with down regulation of telomerase activity to increase sensitivity to TXL to enhance apoptosis in glioblastoma cells. Thus, combination of retinoid and TXL could be an effective therapeutic strategy for controlling the growth of glioblastoma.     

Chemoprevention of 7,12-Dimethylbenz[a]anthracene-induced Mammary Carcinogenesis in Rat by the Combined Actions of Selenium, Magnesium, Ascorbic Acid and Retinyl Acetate

The chemopreventive actions of sodium selenite (SS), magnesium chloride (MC), ascorbic acid (AA) and retinyl acetate (RA), given singly or in combinations, on mammary carcinogenesis induced by 30 mg of 7,12-dimethylbenz[ a ]anthracene (DMBA) in female adult rats were evaluated. Administration of modulators was carried out from the age of 40±3 days to 240±3 days. When DMBA alone was given 100% of the rats developed mammary tumors. When modulators were given singly the tumor incidences were reduced to 51.77% (SS), 46.4% (MC), 57.1% (AA) and 48.1% (RA). When the modulators were given in combination of twos, the tumor incidences were further reduced to 29.5% (SS + MC), 31% (SS + AA), 29.6% (SS + RA), 25.9% (MC + AA), 31.8% (MC + RA) and 34.6% (AA + RA). Administration of modulators in combinations of threes resulted in still further reduction of tumor incidences to 22.2% (SS + MC + AA), 19.2% (SS + MC + RA), 16% (MC + AA + RA) and 23.1% (AA + RA + SS). When all four modulators were given concurrently the tumor incidence was only 12%. Further, the number of tumors per tumor-bearing animal declined with the increase in the number of agents used in combination for modulation.     

视黄酸代谢与常见消化道肿瘤关系的研究进展

视黄酸是维生素A最重要的代谢产物,在调控细胞分化、生长,调节免疫功能,维持上皮细胞完整性等生理过程中起着至关重要的作用。其生理功能的发挥是通过与其特异性受体结合,调节靶细胞目的基因转录,进而激活下游信号通路来完成。而机体视黄酸浓度主要由视黄醇的有效性、相关转运因子、视黄酸合成酶和视黄酸分解酶来决定。在我国,消化道肿瘤是一种高发病率、高死亡率的疾病,常见的如口咽癌、食管癌、胃癌和结直肠癌,这些疾病严重威胁人类身体健康,降低人们生活质量。近年来,有研究显示,消化道肿瘤组织中存在视黄酸代谢酶及因子表达的异常,并且一些消化道肿瘤的危险因素,如槟榔、幽门螺杆菌、高脂饮食等会影响视黄酸合成酶、视黄酸分解酶及其相关因子的表达和功能,进而影响视黄酸调控的下游信号通路,最终影响肿瘤的发生、发展。本文主要就视黄酸的代谢及其与常见消化道肿瘤之间关系的研究进展做一综述,为消化道肿瘤的分子机制研究及营养预防提供理论依据。     

New Insights into 4-Amino-2-tri-fluoromethyl-phenyl Ester Inhibition of Cell Growth and Migration in the A549 Lung Adenocarcinoma Cell Line

Objective: The present study was designed to investigate the probable mechanisms of synthetic retinoid4-amino-2-tri-fluoromethyl-phenyl ester (ATPR) inhibition of the proliferation and migration of A549 humanlung carcinoma cells. Materials and Methods: After the A549 cells were treated with different concentrationsof ATPR or all-trans retinoic acid (ATRA) for 72 h, scratch-wound assays were performed to assess migration.Immunofluorescence was used to determine the distribution of CAV1 and RXRα, while expression of CAV1,MLCK, MLC, P38, and phosphorylation of MLC and P38 were detected by Western blotting. Results: ATPRcould block the migration of A549 cells. The relative migration rate of ML-7 group had significantly decreasedcompared with control group. In addition, ATPR decreased the expression of a migration related proteins,MLCK, and phosphorylation of MLC and P38. ATPR could also influence the expression of RARs or RXRs. Atthe same time, CAV1 accumulated at cell membranes, and RXRα relocated to the nucleus after ATPR treatment.Conclusions: Caveolae may be implicate in the transport of ATPR to the nucleus. Change in the expression anddistribution of RXRα may be implicated in ATPR inhibition of A549 cell proliferation. The mechanisms of ATPRreduction in A549 cell migration may be associated with expression of MLCK and phosphorylation of MLC andP38.     

Role of vitamin A in the evolution of cholesteatoma

The role of vitamin A in the maintenance of epithelial integrity is well known. Several animal studies have dealt with the induction of cholesteatoma in vitamin A deficiency states and prevention and treatment of otitis media with vitamin A treatment. We treated five patients of cholesteatoma with vitamin A oral supplements and no other treatment and found significant resolution of cholesteatoma in four patients. Though this may not be an explanation in every case of cholesteatoma, our study highlights that there is a subset of patients with vitamin A deficient cholesteatoma who could substantially benefit from intervention with this wonderful vital amine.     

An evaluation of serum microelement concentrations in lung cancer and matched non-cancer patients to determine the risk of developing lung cancer: a preliminary study.

In a case-control study to determine the risk of developing lung cancer, the serum levels of vitamins A and E, carotene and selenium were determined in 31 patients, newly diagnosed as having lung cancer, and in matched controls, the said controls being selected from outpatients with no cancer. A significant, inverse association was found between serum vitamins A and E and lung cancer. The relative risk for the low vs high tertiles were, respectively, 5.94 for serum vitamin A and 8.44 for serum vitamin E. Taking histological cancer subtype into account, no relation was revealed between the microelements and squamous cell carcinoma of the lung. The relative risk for lung cancer was 6.50, however, when three, or all four, microelement levels were in the lowest tertile, compared with there being fewer than three in the lowest tertile. Even when three microelements, excluding vitamin E which had the most significant inverse association with lung cancer, were considered, the relative risk was 7.50 when any two or all three were in the lowest tertile, compared with there being just one microelement or none at all in the lowest tertile. A combined effect of vitamins A and E, carotene and selenium on the development of lung cancer has, therefore, been suggested. Further studies will thus be necessary to elucidate the cumulative effect of the serum micronutrients and trace elements, as well as the effect of single elements, on the development of lung cancer.     

Phototoxicity of Herbal Plants and Herbal Products

Plants are used by humans in daily life in many different ways, including as food, herbal medicines, and cosmetics. Unfortunately, many natural plants and their chemical constituents are photocytotoxic and photogenotoxic, and these phototoxic phytochemicals are widely present in many different plant families. To date, information concerning the phototoxicity and photogenotoxicity of many plants and their chemical constituents is limited. In this review, we discuss phototoxic plants and their major phototoxic constituents; routes of human exposure; phototoxicity of these plants and their constituents; general mechanisms of phototoxicity of plants and phototoxic components; and several representative phototoxic plants and their photoactive chemical constituents.     

Cytotoxic Effects of Vitamin A in Combination with Vincristine, Daunorubicin and 6-Thioguanine upon Cells from Lymphoblastic Leukemic Patients

We studied whether isotretinoin potentiated the effects of vincristine (VCR), daunorubicin (DNR), and 6-thioguanine (6-TG) against cells obtained from 24 patients with acute lymphoblastic leukemia (ALL). Treatment with 5 μg /ml isotretinoin alone resulted in a leukemic cell survival of 82%± 28.1%. So isotretinoin is toxic to ALL cells. Dose-response curves were obtained for VCR, DNR and 6-TG in the presence and absence of isotretinoin Isotretinoin showed additive leukemic cell kills in combination with VCR and DNR, When corrected for cell kill by isotretinoin alone, it appeared that isotretinoin did not significantly enhance leukemic cell kills by VCR, DNR and 6-TG. No differences were found between samples from patients at initial diagnosis and at relapse with respect to cell kill by isotretinoin alone and with respect to a possible synergistic effect of isotretinoin and the cytostatic drugs. It is concluded that isotretinoin has additive antileukemic effects in combination with VCR or DNR. However, isotretinoin does not potentiate the antileukemic effects of VCR, DNR and 6-TG against leukemic cells obtained from patients with ALL.     

Prevention of Prostate Cancer with Vitamins - Current Perspectives

Cancer prostate is the most common solid malignancy in males of developed countries. With increasingknowledge of the aetiology, pathogenesis and natural history of the disease, influences of dietary factors onprostate cancer development have become more evident. There is ample evidence in the literature of significanceof dietary constituents for prostate cancer including vitamins A, D and E. Different vitamins have been foundto effect the growth and proliferation of prostate cancer cells as evident in epidemiological, experimental andclinical studies. Various factors play the major role in determining the relationship between these vitamins andprostate cancer in terms of environmental, pharmacological, or genetic aspects. To explore these aspects, thepresent article reviews the literature on the present status of vitamin use for prevention and management ofprostate cancer.     

Retinoids and the control of growth/death decisions in human neuroblastoma cell lines

Cell proliferation, the balance between mitosis and apoptosis is the result of the continuous integration of a number of different signal transduction pathways stimulated in a cell at any given point in its life. Neuroblastoma cells regulate the switch between mitosis and death, according both to intrinsic factors and extrinsic factors, such as growth factor withdrawal and action of the vitamin A derivative, retinoic acid. In this review, we describe the balance of some factors regulating growth and death of human neuroblastoma cells in vitro. These dynamic studies are necessarily performed on cell lines, which offer controlled conditions enabling the disection of the complex stimuli mediating survival and growth (IGF, trk, BDNF) and death (transglutaminase, free radicals, Bcl-2). Although the conclusions drawn may therefore not be directly applicable to tumour cells in vivo, the results herein discussed are of sufficient significance to warrant in vivo relevance.     

Vitamin supplement use and risk for breast cancer: the Shanghai Breast Cancer Study

Objective The influence of vitamin supplements on breast cancer risk is unclear and the interactive effects of dietary and supplemental sources are unknown. This study investigated (1) the association between self-reported vitamin supplement use (multivitamin, A, B, C, and E) and breast cancer and (2) the combined effect of vitamin supplements in relation to dietary vitamin intakes on breast cancer risk. Methods The Shanghai Breast Cancer Study was a population-based case-control study conducted in Shanghai in 1996-1998 (Phase I) and 2002-2004 (Phase II). Participants were aged 25-64 (Phase I) and 20-70 years (Phase II). The analyses included 3,454 incident breast cancer cases and 3,474 controls. Unconditional logistic regression models were used to determine adjusted odds ratios (ORs) for breast cancer risk associated with vitamin supplement use. Results Overall, breast cancer risk was not related to any vitamin supplement intake. However, a 20% reduction in breast cancer risk was observed with vitamin E supplement use among women with low-dietary vitamin E intake (OR = 0.8; 95% confidence interval (CI), 0.6-1.0). A non-significant 20% risk reduction was observed among vitamin B supplement users with low B dietary intake (OR = 0.8; 95% CI, 0.6-1.1). Frequent use of a vitamin B supplement was adversely associated with breast cancer risk among those with high dietary vitamin B intake (OR = 1.4; 95% CI: 0.9-2.1; P for interaction = 0.07). Conclusions This study suggests that vitamins E and B supplements may confer protection against breast cancer among women who have low dietary intake of those vitamins.