Multidrug-resistant cancer cells are sensitive to abietane diterpenoids from Plectranthus species
2022
Аутори:
Jovanović, MirnaBangay, Gabrielle
Jovanović Stojanov, Sofija
Dragoj, Miodrag
Stepanović, Ana
Lupšić, Ema
Podolski-Renić, Ana
Dinić, Jelena
Rijo, Patricia
Pešić, Milica
Остала ауторства
Milutinović, MilicaТип документа:
Конференцијски прилог (Објављена верзија)
,
© 2022 by the Serbian Plant Physiology Society
Метаподаци
Приказ свих података о документуАпстракт:
Plants of the genus Plectranthus (Lamiaceae) are used in traditional medicine. Here, the anti-cancer effects of the three abietane diterpenoid derivatives from Plectranthus species are described. Compounds’ effects (comp. 1 = VI31.1.1, comp. 2 = VI20.1.1, comp. 3 = RoyBz) were tested
in human lung cancer cells, in sensitive NCI-H460 and chemoresistant NCI-H460/R, as well as in colon cancer cells, sensitive DLD1, and hemoresistant DLD1-TxR. The resistant cells were more sensitive than corresponding parental cells to 1 and 2 in MTT assay, with IC50 values ranging from 3 to 10 μM. For the most potent 3 (IC50 as low as 1 μM), resistant cells had up to 2 times higher IC50 values than sensitive cells. The growth inhibition effect by all three compounds was more ronounced in cancer cells, compared to normal human fibroblasts (MRC-5). Only 2 induced a significant cell death effect showing 70% non-viable cells in NCI-H460. The effect the compoundsmight have on the P-gp extrusion pump was also tested using doxorubicin and rhodamine 123 accumulation assays. Compounds 1 and 2 caused a significant increase in the accumulation of both P-gp substrates, doxorubicin, and rhodamine 123. The compounds isolated from Plectranthus showed anticancer potential in lung and colon cancer cells. Importantly, they displayed colateral sensitivity - a phenomenon when the chemoresistant cells are more sensitive to the compounds than corresponding sensitive cells. The compounds inhibited the P-gp activity implying MDR modulating potential.
Кључне речи:
Plectranthus; abietane diterpenoid; anticancer effectФинансирање / пројекти:
- STSM grant awarded by STRATAGEM COST Action CA17104 “New diagnostic and therapeutic tools against multidrug resistant tumours”.
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
У:
- Milutinović M, editor. Book of Abstracts: 4th International Conference on Plant Biology and 23rd SPPS Meeting; 2022 6-8; Belgrade, Serbia. Belgrade: Serbian Plant Physiology Society; 2022. p. 108.