Akademik Veri Yönetim Sistemi
International Journal For Research In Biology & Pharmacy, cilt.7, sa.8, ss.1-8, 2021 (Hakemli Dergi)
Objective: Despite emerging new treatments, there is a need for new anti-cancer agents for childhood solid tumors. Sesquiterpene lactones(SLs) are plant-derived secondary metabolites with anti-cancer properties. Dehydroleucodine(DhL) is a guaianolide-type SL isolated from Artemisia douglasiana (Asteraceae). In this study, the cytotoxic, antiproliferative, apoptotic effects of DhL on childhood solid tumors including Ewing sarcoma(ES), Hepatoblastoma(HBL), and Neuroblastoma(NB) were investigated in in-vitro conditions.
Material and Methods: In this study, NB cell line KELLY, ES cell line SK-ES-1, and HBL cell line Hep-G2 were used. Cell lines were cultured and LD50 doses of DhL and Cisplatin(CDDP) were calculated by MTT. Effective doses were applied to all cell lines, and percentages of apoptosis and necrosis were determined by Annexin V-PI test in flow cytometry. Morphological changes in cells were examined by toluidine blue staining. Immunocytochemical(ICC) examinations were performed with Caspase3,8, and 9 to determine the mechanism of apoptosis as Ki67 proliferation index. Statistical analysis was performed using the Mann-Whitney U test at a statistical significance level of p<0,05.
Results: LD50 doses of DhL and CDDP were determined as
75µM, 100µM for Kelly; 50µM, 100µM for HEP-G2; and 100µM, 300µM for SK-ES-1.
The intrinsic pathway in all cell lines was more pronounced in DhL, which reduced proliferation leading to apoptosis. DhL reduced proliferation less than CDDP and resulted in similar apoptotic cell death.
Conclusions: DhL showed a
statistically significant anti-cancer activity similar to CDDP. It exerted this
effect through apoptosis. Planning in-vivo experiments about this agent and
explaining its molecular mechanisms, investigating the effects of other SL on
childhood cancers are among our future goals.