Department of Biochemistry, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Três de Maio 100, São Paulo, Brazil.
Planta Med. 2013 Mar;79(3-4):227-35. doi: 10.1055/s-0032-1328156. Epub 2013 Jan 23.
In cancer tumors, growth, invasion, and formation of metastasis at a secondary site play a pivotal role, participating in diverse processes in the development of the pathology, such as degradation of extracellular matrix. Bauhinia seeds contain relatively large quantities of peptidase inhibitors, and two Bauhinia inhibitors were obtained in a recombinant form from the Bauhinia bauhinioides species, B. bauhinoides cruzipain inhibitor, which is a cysteine and serine peptidase inhibitor, and B. bauhinioides kallikrein inhibitor, which is a serine peptidase inhibitor. While recombinant B. bauhinoides cruzipain inhibitor inhibits human neutrophil elastase cathepsin G and the cysteine proteinase cathepsin L, recombinant B. bauhinioides kallikrein inhibitor inhibits plasma kallikrein and plasmin. The effects of recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor on the viability of tumor cell lines with a distinct potential of growth from the same tissue were compared to those of the clinical cytotoxic drug 5-fluorouracil. At 12.5 µM concentration, recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor were more efficient than 5-fluorouracil in inhibiting MKN-28 and Hs746T (gastric), HCT116 and HT29 (colorectal), SkBr-3 and MCF-7 (breast), and THP-1 and K562 (leukemia) cell lines. Additionally, recombinant B. bauhinoides cruzipain inhibitor inhibited 40 % of the migration of Hs746T, the most invasive gastric cell line, while recombinant B. bauhinioides kallikrein inhibitor did not affect cell migration. Recombinant B. bauhinioides kallikrein inhibitor and recombinant B. bauhinoides cruzipain inhibitor, even at high doses, did not affect hMSC proliferation while 5-fluorouracil greatly reduced the proliferation rates of hMSCs. Therefore, both recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor might be considered for further studies to block peptidase activities in order to target specific peptidase-mediated growth and invasion characteristics of individual tumors, mainly in patients resistant to 5-fluorouracil chemotherapy.
在癌症肿瘤中，生长、侵袭和转移的形成在二级部位发挥着关键作用，参与了病理学发展的多种过程，如细胞外基质的降解。羊蹄甲种子含有相对大量的肽酶抑制剂，两种羊蹄甲抑制剂以重组形式从羊蹄甲属物种中获得，即羊蹄甲 cruzain 抑制剂，它是一种半胱氨酸和丝氨酸肽酶抑制剂，以及羊蹄甲 kallikrein 抑制剂，它是一种丝氨酸肽酶抑制剂。重组羊蹄甲 cruzain 抑制剂抑制人中性粒细胞弹性蛋白酶 cathepsin G 和半胱氨酸蛋白酶 cathepsin L，而重组羊蹄甲 kallikrein 抑制剂抑制血浆激肽和纤溶酶。将重组羊蹄甲 cruzain 抑制剂和重组羊蹄甲 kallikrein 抑制剂对来自同一组织的具有明显生长潜力的肿瘤细胞系的活力的影响与临床细胞毒性药物 5-氟尿嘧啶进行了比较。在 12.5 µM 浓度下，重组羊蹄甲 cruzain 抑制剂和重组羊蹄甲 kallikrein 抑制剂在抑制 MKN-28 和 Hs746T（胃）、HCT116 和 HT29（结肠）、SkBr-3 和 MCF-7（乳腺）和 THP-1 和 K562（白血病）细胞系方面比 5-氟尿嘧啶更有效。此外，重组羊蹄甲 cruzain 抑制剂抑制了最具侵袭性的胃细胞系 Hs746T 中 40%的迁移，而重组羊蹄甲 kallikrein 抑制剂则不影响细胞迁移。重组羊蹄甲 cruzain 抑制剂和重组羊蹄甲 kallikrein 抑制剂，即使在高剂量下，也不会影响 hMSC 的增殖，而 5-氟尿嘧啶则大大降低了 hMSC 的增殖率。因此，重组羊蹄甲 cruzain 抑制剂和重组羊蹄甲 kallikrein 抑制剂都可以考虑进一步研究，以阻断肽酶活性，从而针对特定的肽酶介导的生长和侵袭特征，主要是针对对 5-氟尿嘧啶化疗有抗药性的患者。
