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Diclofenac Enhances Docosahexaenoic Acid-Induced Apoptosis in Vitro in Lung Cancer Cells

1
Department of Foundational Sciences, College of Medicine, Central Michigan University, Warriner Hall, 319, Mt Pleasant, MI 48859, USA
2
Department of Pharmaceutical Sciences, Ferris State University, College of Pharmacy, 220 Ferris Dr, Big Rapids, MI 49307, USA
3
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(9), 2683; https://doi.org/10.3390/cancers12092683
Received: 9 September 2020 / Accepted: 17 September 2020 / Published: 20 September 2020
(This article belongs to the Section Cancer Therapy)
Polyunsaturated 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. View Full-Text
Keywords: polyunsaturated fatty acids; docosahexaenoic acid; K-Ras; cyclooxygenase; non-steroidal anti-inflammatory drugs; diclofenac; lung cancer; nanostring polyunsaturated fatty acids; docosahexaenoic acid; K-Ras; cyclooxygenase; non-steroidal anti-inflammatory drugs; diclofenac; lung cancer; nanostring
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MDPI and ACS Style

Poku, R.A.; Jones, K.J.; Van Baren, M.; Alan, J.K.; Amissah, F. Diclofenac Enhances Docosahexaenoic Acid-Induced Apoptosis in Vitro in Lung Cancer Cells. Cancers 2020, 12, 2683. https://doi.org/10.3390/cancers12092683

AMA Style

Poku RA, Jones KJ, Van Baren M, Alan JK, Amissah F. Diclofenac Enhances Docosahexaenoic Acid-Induced Apoptosis in Vitro in Lung Cancer Cells. Cancers. 2020; 12(9):2683. https://doi.org/10.3390/cancers12092683

Chicago/Turabian Style

Poku, Rosemary A., Kylee J. Jones, Megan Van Baren, Jamie K. Alan, and Felix Amissah. 2020. "Diclofenac Enhances Docosahexaenoic Acid-Induced Apoptosis in Vitro in Lung Cancer Cells" Cancers 12, no. 9: 2683. https://doi.org/10.3390/cancers12092683

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