Koczurkiewicz-Adamczyk Paulina, Grabowska Karolina, Karnas Elżbieta, Piska Kamil, Wnuk Dawid, Klaś Katarzyna, Galanty Agnieszka, Wójcik-Pszczoła Katarzyna, Michalik Marta, Pękala Elżbieta, Fuchs Hendrik, Podolak Irma
Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688 Kraków, Poland.
Institute of Diagnostic Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany.
Pharmaceutics. 2023 Apr 28;15(5):1350. doi: 10.3390/pharmaceutics15051350.
Saponins are plant metabolites that possess multidirectional biological activities, among these is antitumor potential. The mechanisms of anticancer activity of saponins are very complex and depend on various factors, including the chemical structure of saponins and the type of cell they target. The ability of saponins to enhance the efficacy of various chemotherapeutics has opened new perspectives for using them in combined anticancer chemotherapy. Co-administration of saponins with targeted toxins makes it possible to reduce the dose of the toxin and thus limit the side effects of overall therapy by mediating endosomal escape. Our study indicates that the saponin fraction CIL1 of L. can improve the efficacy of the EGFR-targeted toxin dianthin (DE). We investigated the effect of cotreatment with CIL1 + DE on cell viability in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, on proliferation in a crystal violet assay (CV) and on pro-apoptotic activity using Annexin V/7 Actinomycin D (7-AAD) staining and luminescence detection of caspase levels. Cotreatment with CIL1 + DE enhanced the target cell-specific cytotoxicity, as well as the antiproliferative and proapoptotic properties. We found a 2200-fold increase in both the cytotoxic and antiproliferative efficacy of CIL1 + DE against HER14-targeted cells, while the effect on control NIH3T3 off-target cells was less profound (6.9- or 5.4-fold, respectively). Furthermore, we demonstrated that the CIL1 saponin fraction has a satisfactory in vitro safety profile with a lack of cytotoxic and mutagenic potential.
皂苷是具有多向生物活性的植物代谢产物，其中包括抗肿瘤潜力。皂苷的抗癌活性机制非常复杂，取决于多种因素，包括皂苷的化学结构及其靶向的细胞类型。皂苷增强各种化疗药物疗效的能力为其在联合抗癌化疗中的应用开辟了新的前景。将皂苷与靶向毒素共同给药能够降低毒素剂量，从而通过介导内体逃逸来限制整体治疗的副作用。我们的研究表明，地锦草的皂苷组分CIL1可以提高表皮生长因子受体（EGFR）靶向毒素相思豆毒蛋白（DE）的疗效。我们通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法研究了CIL1 + DE联合处理对细胞活力的影响，通过结晶紫法（CV）研究了对细胞增殖的影响，并使用膜联蛋白V/7-氨基放线菌素D（7-AAD）染色和半胱天冬酶水平的发光检测研究了对促凋亡活性的影响。CIL1 + DE联合处理增强了靶细胞特异性细胞毒性以及抗增殖和促凋亡特性。我们发现，CIL1 + DE对HER14靶向细胞的细胞毒性和抗增殖疗效均增加了2200倍，而对对照NIH3T3非靶向细胞的影响则较小（分别为6.9倍或5.4倍）。此外，我们证明CIL1皂苷组分在体外具有令人满意的安全性，没有细胞毒性和致突变潜力。
