Abstract
Simple SummaryPolyunsaturated fatty acids (PUFAs) and non-steroidal anti-inflammatory drugs (NSAIDs) have limited anticancer capacities when used alone. We examined whether combining NSAIDs with docosahexaenoic (DHA) would increase their anticancer activity on lung cancer cell lines. Our results indicate that combining DHA and NSAIDs increased their anticancer activities by altering the expression of critical proteins in the RAS/MEK/ERK and PI3K/Akt pathways. The data suggest that DHA combined with low dose diclofenac provides more significant anticancer potential, which can be further developed for chemoprevention and adjunct therapy in lung cancer.Polyunsaturated fatty acids (PUFAs) and non-steroidal anti-inflammatory drugs (NSAIDs) show anticancer activities through diverse molecular mechanisms. However, the anticancer capacities of either PUFAs or NSAIDs alone is limited. We examined whether combining NSAIDs with docosahexaenoic (DHA), commonly derived from fish oils, would possibly synergize their anticancer activity. We determined the viability of lung cancer cell lines (NCI-H1573, A549, NCI-H1299, and NCI-H1975) after exposure to DHA and various NSAIDs. We further conducted cell apoptosis assays and analyzed apoptosis-associated proteins and some key proteins in the RAS/MEK/ERK and PI3K/Akt pathways using western blot analysis. We also determined the impact of the treatment on the expression of inducible cancer-related genes using nCounter PanCancer Pathways gene expression analysis. The results showed that the combination of DHA and NSAIDs increased suppression of cell viability in all the lung cancer cell lines tested compared to each of the compounds used alone, with diclofenac being the most potent NSAID tested. This synergistic effect is especially significant in A549 and NCI-H1573 cells. The combination treatment was more effective at inhibiting clonogenic cell growth and anchorage-independent growth in soft agar, inducing caspase-dependent apoptosis, and altering expression of critical proteins in the RAS/MEK/ERK and PI3K/Akt pathways. The data from this study demonstrate that DHA combined with low dose diclofenac provides greater anticancer potential, which can be further developed for chemoprevention and adjunct therapy in lung cancer.
Highlights
Lung cancer continues to pose a serious health problem in the US as the second most commonly diagnosed cancer with an estimated 228,820 new diagnoses and 135,720 deaths likely to occur in 2020.Cancers 2020, 12, 2683; doi:10.3390/cancers12092683 www.mdpi.com/journal/cancerslung cancer is projected to account for one-quarter of all cancer-related deaths
We examine the effects of the combination of ω-3 polyunsaturated fatty acids (PUFAs) and non-steroidal anti-inflammatory drugs (NSAIDs) on a panel of lung cancer cells
In combination with diclofenac (25 μM) (Figure 4C,D). These results further indicate that co-treatment with DHA and diclofenac inhibited tumorigenicity of NCI-H1573 and A549 cells
Summary
Lung cancer continues to pose a serious health problem in the US as the second most commonly diagnosed cancer with an estimated 228,820 new diagnoses and 135,720 deaths likely to occur in 2020. Lung cancer is projected to account for one-quarter of all cancer-related deaths. 5-year survival rate of only 19% for all lung cancer stages combined [1], there is a need for effective preventive and therapeutic strategies to combat this disease. Fish oil [4,5,6]. These two classes of medications, mostly available “over-the-counter” have been under extensive investigation in the past few decades for their beneficial health effects
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