Photochemically generated elemental selenium forms conjugates with serum proteins that are preferentially cytotoxic to leukemia and selected solid tumor cells.
Photochemically generated elemental selenium forms conjugates with serum proteins that are preferentially cytotoxic to leukemia and selected solid tumor cells.
复制标题
DOI：
10.1111/j.1751-1097.2012.01078.x
复制
发表时间：
2012-03
影响因子：
3.3
通讯作者：
Sieber F
中科院分区：
文献类型：
--
作者：
Daziano JP;Günther WH;Krieg M;Tsujino I;Miyagi K;Anderson GS;Sampson RW;Ostrowski MD;Muir SA;Bula RJ;Sieber F
本研究的目的是确定光产物是否以及如何促进部花青介导的 PDT 的抗肿瘤作用。对部花青 540 的一组巴比妥酸、硫代巴比妥酸和硒代巴比妥酸类似物进行光漂白，并通过吸收、荧光发射、质量、能量色散 X 射线和 X 射线光电子能谱对所得光产物进行表征，并测试针对肿瘤细胞系和新鲜移植的骨髓细胞的细胞毒性活性。虽然所有染料都很容易光漂白，但只有硒染料的光产物表现出细胞毒性活性。用微摩尔浓度的硒化物衍生的光产物孵育一小时足以使白血病/淋巴瘤细胞减少≥10,000倍，同时保留几乎所有正常的CD34阳性骨髓细胞。在测试的 6 个多重耐药肿瘤细胞系中，有 5 个对光产物比相应的野生型细胞系更敏感或更敏感。细胞毒活性的物理化学特征表明它由元素硒的亚纳米颗粒和（脂）蛋白的缀合物组成。细胞毒性硒蛋白缀合物的发现提供了一个罕见的例子，说明光产物对 PDT 的抗肿瘤作用有重大贡献，并挑战了长期以来认为零氧化态硒具有生物惰性的观点。以我们的硒蛋白缀合物为模型的药物可能被证明可用于治疗白血病。
The objective of this study was to determine if and how photoproducts contribute to the anti-tumor effect of merocyanine-mediated PDT. A panel of barbituric, thiobarbituric and selenobarbituric acid analogues of Merocyanine 540 was photobleached, and the resulting photoproducts were characterized by absorption, fluorescence emission, mass, energy dispersive X-ray, and X-ray photoelectron spectroscopy, and tested for cytotoxic activity against tumor cell lines and freshly explanted bone marrow cells. While all dyes were readily photobleached, only photoproducts of selone dyes showed cytotoxic activity. One-hour incubations with micromolar concentrations of selone-derived photoproducts were sufficient to reduce leukemia/lymphoma cells ≥10,000 fold while preserving virtually all normal CD34-positive bone marrow cells. Of 6 multi-drug resistant tumor cell lines tested, 5 were as sensitive or more sensitive to photoproducts than the corresponding wild-type lines. Physicochemical characterizations of the cytotoxic activity indicated that it consisted of conjugates of subnano particles of elemental selenium and (lipo)proteins. The discovery of cytotoxic Se-protein conjugates provides a rare example of photoproducts contributing substantially to the anti-tumor effect of PDT and challenges the long-held view that Se in oxidation state zero is biologically inert. Agents modeled after our Se-protein conjugates may prove useful for the treatment of leukemia.
登录
查看更多内容
影响因子：
2.7
作者：
SIEBER, F;STUART, RK;SENSENBRENNER, LL
通讯作者：
SENSENBRENNER, LL
DOI：
10.1016/s1011-1344(02)00411-6
发表时间：
2003-02-01
影响因子：
5.4
作者：
Anderson, GS;Tsujino, I;Sieber, F
通讯作者：
Sieber, F
影响因子：
3.3
作者：
Anderson, GS;Gunther, WHH;Sieber, F
通讯作者：
Sieber, F
DOI：
10.1080/10426509208045864
发表时间：
1992-01-01
影响因子：
1.3
作者：
GUNTHER, WHH;SEARLE, R;SIEBER, F
通讯作者：
SIEBER, F
DOI：
10.1016/s1011-1344(03)00073-3
发表时间：
2003-07-01
影响因子：
5.4
作者：
Miyagi, K;Sampson, RW;Sieber, F
通讯作者：
Sieber, F