Dataset Information

New Paradigms to Assess Consequences of Long-Term, Low-Dose Curcumin Exposure in Lung Cancer Cells.

ABSTRACT: 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.

SUBMITTER: Smagurauskaite G

PROVIDER: S-EPMC7024150 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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New Paradigms to Assess Consequences of Long-Term, Low-Dose Curcumin Exposure in Lung Cancer Cells.

Smagurauskaite Gintare G Mahale Jagdish J Brown Karen K Thomas Anne L AL Howells Lynne M LM

Molecules (Basel, Switzerland) 20200116 2

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. IC<sub>50</sub>s for curcumin, cisplatin, and pemetrexed in A549, PC9, and PC9ER NSCLC cells were ...[more]

PMID: 31963196

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Project description:ImportanceLow-dose aspirin use for chemoprevention of lung cancer risk remains controversial.ObjectivesTo investigate the association between low-dose aspirin use and lung cancer risk, and to identify specific subgroups that may derive the most benefit from low-dose aspirin use.Design, setting, and participantsThis nationwide, retrospective, cohort study used data from the Korean National Health Information Database from 2002 to 2015. Data analyses were performed from October 2016 to December 2018. Eligible participants (n = 12 969 400) were people aged 40 to 84 years who had undergone national health screening between 2009 and 2010 and had no history of lung cancer between 2006 and 2010 and no standard-dose aspirin use for 6 months between 2002 and 2010.Main outcomes and measuresThe duration of low-dose aspirin use between January 2002 and December 2010 was calculated for each participant. Lung cancer was defined as the first recorded diagnosis of lung cancer-using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and expanding benefit coverage-between January 2011 and December 2015.ResultsA total of 63 040 participants with a mean (SD) age of 66.4 (9.3) years received a diagnosis of lung cancer. Of these, 45 156 (71.6%) were men. The incidence rate of lung cancer was 98.8 per 100 000 person-years. The duration of low-dose aspirin use was none for 10 987 417 participants (84.7%), 1 to 2 years for 750 992 participants (5.8%), 3 to 4 years for 506 945 participants (3.9%), 5 to 6 years for 371 062 participants (2.9%), 7 to 8 years for 240 528 participants (1.9%), and 9 years for 112 456 participants (0.9%). Compared with no aspirin use, 5 to 6 years (adjusted hazard ratio, 0.96 [95% CI, 0.92-0.99]), 7 to 8 years (adjusted hazard ratio, 0.94 [95% CI, 0.90-0.99]), and 9 years (adjusted hazard ratio, 0.89 [95% CI, 0.84-0.94]) of aspirin use were significantly associated with reduced lung cancer risk. After stratified analysis, a significant reduction of lung cancer risk was observed among people aged 65 years or older and among people without diabetes.Conclusions and relevanceAlthough the use of low-dose aspirin for more than 5 years was associated with decreased risk of lung cancer, particularly among elderly participants and among people without diabetes, the observed effect size was quite modest. Future prospective studies are needed to determine whether there is a causal association.

Dataset Information

New Paradigms to Assess Consequences of Long-Term, Low-Dose Curcumin Exposure in Lung Cancer Cells.

Publications

New Paradigms to Assess Consequences of Long-Term, Low-Dose Curcumin Exposure in Lung Cancer Cells.

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