The anticancer effects of triterpene saponin deglucocyclamine isolated from Cyclamen hederifolium
2023
Аутори:
Pajović, MilicaStanković Jeremić, Jovana
Jovanović Stojanov, Sofija
Gođevac, Dejan
Pešić, Milica
Podolski-Renić, Ana
Тип документа:
Конференцијски прилог (Објављена верзија)
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© 2023 by the Serbian Associaton for Cancer Research
Метаподаци
Приказ свих података о документуАпстракт:
Background: Following the traditional Serbian use of cyclamen tubers in the treatment of the most aggressive forms of lung cancer, we performed methanolic extraction of fresh tubers of Cyclamen hederifolium to isolate and identify bioactive constituents. The triterpene saponin deglucocyclamine (SDGC) was identified as a major constituent of cyclamen extract, and its anticancer effects were studied using a panel of NCI-60 cell lines and primary cell cultures obtained from patients with non-small cell lung cancer (NSCLC). Material and Methods: The cyclamen tubers were ground, lyophilized, and extracted with methanol at room temperature with the use of an ultrasonic bath. The part of the methanol extract was further fractionated by dissolving in H2O and then washed with CH2Cl2. The water layer was extracted with n-BuOH. The butanol extract was fractionated by isocratic CC on silica gel with CHCl3−MeOH−H2O eluent. This resulted in the isolation of triterpene (SDGC, C52H84O22) which was identified using 1D and 2D NMR spectra. SDGC was tested at 10 µM against a panel of NCI-60 cancer cell lines and then over a concentration range of 0.01-100 µM using the sulforhodamine B (SRB) assay. SDGC was also tested in the concentration range of 0.01-10 µM against 5 primary patient-derived NSCLC cell cultures (2 stage IB, 2 stage IIA, and 1 stage IIB) using the MTT assay. Cell death analysis was performed in patient-derived NSCLC cells using annexin/propidium iodide staining and flow cytometry. Results: SDGC at 10 µM after 72 h significantly inhibited cell growth of all tested cancer cell lines in the NCI-60 panel. Therefore, SDGC IC50 values were evaluated across the entire NCI-60 panel and ranged from 600 nM to 1 µM. In patient-derived NSCLC cells, SDGC IC50 values were between 1.3 µM and 4.6 µM after 72 h of treatment. SDGC at 10 µM induced late apoptosis and necrosis, significantly reducing the percentage of viable cells to 40% after 48 h. At the same concentration, cisplatin was ineffective against patient-derived NSCLC cells. Conclusions: The triterpene saponin deglucocyclamine (SDGC), whose anticancer effects have not been studied before, showed promising results against NSCLC, melanoma, colon, breast, ovarian, kidney, prostate, and CNS cancer cell lines, as well as patient-derived NSCLC cells. Further more detailed studies of SDGC at the cellular and molecular level are planned.
Кључне речи:
anticancer; cyclamen; NCI-60; non-small cell lung carcinoma; patient-derived cell cultureУ:
- Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. Belgrade, Serbia: Serbian Associaton for Cancer Research; 2023. p. 61. (Oncology Insights; No. 1).