Bogoeva Vanya P, Petrova Lidiya P, Ivanov Ivan B, Kulina Hristina N, Buchvarov Ivan Ch
Institute of Molecular Biology, Bulgarian Academy of Sciences, Acad. G. Bonchev str., bl. 21, 1113 Sofia, Bulgaria.
Mol Biosyst. 2012 Oct;8(10):2633-6. doi: 10.1039/c2mb25186h.
Many anticancer drugs cannot recognize selectively tumor tissues, and cause destruction to normal ones. Although it is very toxic, cisplatin is still one of the most applied chemotherapeutics used for treatment of sarcomas, carcinomas, etc. It causes severe side effects as a result of the lack of selectivity of the drug to tumor tissue and acquired or intrinsic resistance occurs. Wheat germ agglutinin (WGA) is a lectin that specifically recognizes transformed cells: prostate cancer cells, pancreatic cells etc., and is uptaken into the tumor cells for which it appears to be a suitable target for anticancer agents. A fluorescence spectroscopy method was used to study the interaction of WGA with four metal-based anticancer drugs: cisplatin, Pt porphyrin and two gold porphyrins. The affinity constant (k(D)) for binding of cisplatin with WGA was k(D) = 6.67 ± 2.5 μM. The hyperbolic curve indicated the presence of a single cisplatin binding site. The affinity of Au and Pt porphyrin to WGA (k(D) = 0.08-0.49 μM) is almost two orders of magnitude higher than that for cisplatin. We found that Pt porphyrin could displace fluorescent dye ANS showing an increase in the fluorescence intensity with a concomitant blue shift of the emission maximum suggesting that the compounds accommodate the same binding site. Current research characterizes the metalloanticancer binding capacity of WGA. Our results indicate that four metal-based anticancer agents have high affinity for WGA. Since WGA recognizes transformed cells, the obtained data show that this protein might have putative usage as a drug delivery molecule in cancer.
许多抗癌药物无法选择性地识别肿瘤组织，会对正常组织造成破坏。顺铂虽然毒性很大，但仍是治疗肉瘤、癌等最常用的化疗药物之一。由于该药物对肿瘤组织缺乏选择性，会导致严重的副作用，并且会出现获得性或内在抗性。麦胚凝集素（WGA）是一种凝集素，能特异性识别转化细胞，如前列腺癌细胞、胰腺细胞等，并被摄取到肿瘤细胞中，它似乎是抗癌药物的合适靶点。采用荧光光谱法研究了WGA与四种金属基抗癌药物的相互作用：顺铂、铂卟啉和两种金卟啉。顺铂与WGA结合的亲和常数（k(D)）为k(D)=6.67±2.5μM。双曲线表明存在单个顺铂结合位点。金卟啉和铂卟啉对WGA的亲和力（k(D)=0.08 - 0.49μM）比顺铂高近两个数量级。我们发现铂卟啉可以取代荧光染料ANS，荧光强度增加，同时发射最大值出现蓝移，这表明这些化合物占据相同的结合位点。当前研究表征了WGA的金属抗癌结合能力。我们的结果表明，四种金属基抗癌剂对WGA具有高亲和力。由于WGA能识别转化细胞，所得数据表明该蛋白在癌症中可能具有作为药物递送分子的潜在用途。
