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New paradigms to assess consequences of long-term low-dose curcumin exposure in lung cancer cells.

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journal contribution
posted on 12.05.2020, 08:51 by Lynne Howells, Gintare Smagurauskaite, Jagdish Mahale, Karen Brown, Anne Thomas
Curcumin has been investigated extensively for cancer prevention, but it has been proposed that long-term treatments may promote clonal evolution and gain of cellular resistance, potentially rendering cancer cells less sensitive to future therapeutic interventions. Here, we used long-term, low-dose treatments to determine the potential for adverse effects in non-small cell lung cancer (NSCLC) cells. IC50s for curcumin, cisplatin, and pemetrexed in A549, PC9, and PC9ER NSCLC cells were evaluated using growth curves. IC50s were subsequently re-assessed following long-term, low-dose curcumin treatment and a three-month treatment withdrawal period, with a concurrent assessment of oncology-related protein expression. Doublet cisplatin/pemetrexed-resistant cell lines were created and the IC50 for curcumin was determined. Organotypic NSCLC-fibroblast co-culture models were used to assess the effects of curcumin on invasive capacity. Following long-term treatment/treatment withdrawal, there was no significant change in IC50s for the chemotherapy drugs, with chemotherapy-resistant cell lines exhibiting similar sensitivity to curcumin as their non-resistant counterparts. Curcumin (0.25–0.5 µM) was able to inhibit the invasion of both native and chemo-resistant NSCLC cells in the organotypic co-culture model. In summary, long-term curcumin treatment in models of NSCLC neither resulted in the acquisition of pro-carcinogenic phenotypes nor caused resistance to chemotherapy agents.

Funding

This work was supported by a PhD studentship granted to Gintare Smagurauskaite by Indena S.P.A. Further support was received from Cancer Research UK in conjunction with the UK Department of Health on an Experimental Cancer Medicine Centre grant [C10604/A25151].

History

Citation

Molecules 2020, 25, 366; doi:10.3390/molecules25020366

Version

VoR (Version of Record)

Published in

Molecules

Volume

25

Pagination

366

Publisher

MDPI AG

issn

1420-3049

Acceptance date

14/01/2020

Copyright date

2020

Available date

16/01/2020

Publisher version

https://www.mdpi.com/1420-3049/25/2/366

Language

en

Licence

Exports

University of Leicester Publications

Categories

Licence

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