Anti-inflammatory nitro-fatty acids suppress tumor growth by triggering mitochondrial dysfunction and activation of the intrinsic apoptotic pathway in colorectal cancer cells

Kühn, Benjamin; Brat, Camilla; Fettel, Jasmin; Hellmuth, Nadine; Maucher, Isabelle V.; Bulut, Ufuk; Hock, Katharina J.; Grimmer, Jennifer; Manolikakes, Georg; Rühl, Michael; Kühn, Alessa; Zacharowski, Kai; Matrone, Carmela; Urbschat, Anja; Roos, Jessica; Steinhilber, Dieter; Maier, Thorsten J.

doi:10.1016/j.bcp.2018.06.014

Cited by 21 publications

(21 citation statements)

References 63 publications

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“…POPS was selected because it is one of the abundant PS molecular species detected in some cell types as keratinocytes [18], and tissues as intestinal and lung [19]. Additionally, oleic acid seems to be one of the targets of nitration [20] and nitro-oleic acid is considered a bioactive lipid with anti-inflammatory [21,22], and antioxidant properties [23]. Identification of nitrated/nitroxidized PS species was performed by electrospray ionization mass spectrometry (ESI-MS) and reversed-phase liquid chromatography (LC-MS).…”

Section: Introductionmentioning

confidence: 99%

Profile of Phosphatidylserine Modifications under Nitroxidative Stress Conditions Using a Liquid Chromatography-Mass Spectrometry Based Approach

et al. 2018

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Nitrated lipids have been detected in vitro and in vivo, usually associated with a protective effect. While nitrated fatty acids have been widely studied, few studies reported the nitration and nitroxidation of the phospholipid classes phosphatidylcholine, and phosphatidylethanolamine. However, no information regarding nitrated and nitroxidized phosphatidylserine can be found in the literature. This work aims to identify and characterize the nitrated and nitroxidized derivatives of 1-palmitoyl-2-oleoyl-sn-3-glycero-phosphoserine (POPS), obtained after incubation with nitronium tetrafluoroborate, by liquid chromatography (LC) coupled to mass spectrometry (MS) and tandem MS (MS/MS). Several nitrated and nitroxidized products were identified, namely, nitro, nitroso, nitronitroso, and dinitro derivatives, as well as some nitroxidized species such as nitrosohydroxy, nitrohydroxy, and nitrohydroperoxy. The fragmentation pathways identified were structure-dependent and included the loss of HNO and HNO2 for nitroso and nitro derivatives, respectively. Combined losses of PS polar head group plus HNO or HNO2 and carboxylate anions of modified fatty acyl chain were also observed. The nitrated POPS also showed antiradical potential, demonstrated by the ability to scavenge the ABTS●+ and DPPH● radicals. Overall, this in vitro model of nitration based on LC-MS/MS provided additional insights into the nitrated and nitroxidized derivatives of PS and their fragmentation fingerprinting. This information is a valuable tool for targeted analysis of these modified PS in complex biological samples, to further explore the new clues on the antioxidant potential of nitrated POPS.

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Section: Introductionmentioning

confidence: 99%

Profile of Phosphatidylserine Modifications under Nitroxidative Stress Conditions Using a Liquid Chromatography-Mass Spectrometry Based Approach

et al. 2018

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“…Finally, NFAs suppress tumor growth by causing mitochondrial dysfunction and activation of the intrinsic pathway of apoptosis in colorectal cancer cells. Inhibition of the pro-inflammatory proteins, NF- κ B and 5-lipoxygenase, which are involved in tumorigenesis, is considered a possible mode of action for NFAs, explaining their chemopreventive effects ( Kühn et al, 2018 ).…”

Section: Therapeutic Effects Of Nfamentioning

confidence: 99%

The Emerging Therapeutic Potential of Nitro Fatty Acids and Other Michael Acceptor-Containing Drugs for the Treatment of Inflammation and Cancer

et al. 2020

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dual inhibitor of the human epidermal growth factor receptor 2 and epidermal growth factor receptor, was recently approved by the FDA (2017) and by the EMA (2018) for the treatment of breast cancer. Finally, a number of further Michael acceptor drug candidates are currently under clinical investigation for pharmacotherapy of inflammation and cancer. In this review, we focus on the pharmacology of NFA and other Michael acceptor drugs, summarizing their potential as an emerging class of future antiphlogistics and adjuvant in tumor therapeutics.

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“…In the present study, CTEO showed significant antitumor activity attributable to the presence of fatty acids, which accounted for 78.48% of the total oil (Table 1). Previous studies have demonstrated that fatty acids have significant anti-tumor effects [30]. Butyrate, histone deacetylase inhibitor, is a typical short chain fatty acid, which have significant anti-cancer activity against colon cancer cell line HCT116.…”

Section: Plos Onementioning

confidence: 99%

“…Another very important mechanism used by anticancer agents is cell cycle arrest. If the cancer cell were arrested in any phase of the cell cycle, they are unable to complete cell division and tumor growth is inhibited [30]. Moreover, the proliferative inhibitory effects of CTEO on A549 cells may be at least partly dependent on cyclin protein expressions, because it was noted that CTEO treatment would inhibit cyclin protein expression (Fig 3).…”

Section: Plos Onementioning

confidence: 99%

Croton tiglium essential oil compounds have anti-proliferative and pro-apoptotic effects in A549 lung cancer cell lines

et al. 2020

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As a traditional Chinese medicine, Croton tiglium has the characteristics of laxative, analgesic, antibacterial and swelling. This study aimed to analyze the chemical composition of C. tiglium essential oil (CTEO) extracted from the seeds of C. tiglium and its cytotoxicity and antitumor effect in vitro. Supercritical CO 2 fluid extraction technology was used to extract CTEO and the chemical constituents of the essential oil were identified by comparing the retention indices and mass spectra data taken from the NIST library with those calculated based on the C7-C40 n-alkanes standard. In vitro cytotoxicity of the CTEO was assessed against cancer cell lines (A549) and the human normal bronchial epithelial cells (HBE) using the CCK-8 assay. Proliferation was detected by colony formation experiments. Wound scratch and cell invasion assays were used to detect cell migration and invasion. Levels of apoptotic markers, signaling molecules, and cell cycle regulators expression were characterized by Western blot analysis. As the results, twenty-eight compounds representing 92.39% of the total oil were identified in CTEO. The CTEO has significant antitumor activity on A549 cancer cells (IC 50 48.38 μg/mL). In vitro antitumor experiments showed that CTEO treatment significantly inhibited the proliferation and migration of A549 cells, disrupted the cell cycle process, and reduced the expression levels of cyclin A, cyclin B and CDK1. CTEO can also reduce mitochondrial membrane potential, activate caspase-dependent apoptosis pathway, and finally induce apoptosis. CTEO may become an effective anti-cancer drug and will be further developed for cancer treatment.

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Anti-inflammatory nitro-fatty acids suppress tumor growth by triggering mitochondrial dysfunction and activation of the intrinsic apoptotic pathway in colorectal cancer cells

Cited by 21 publications

References 63 publications

Profile of Phosphatidylserine Modifications under Nitroxidative Stress Conditions Using a Liquid Chromatography-Mass Spectrometry Based Approach

Profile of Phosphatidylserine Modifications under Nitroxidative Stress Conditions Using a Liquid Chromatography-Mass Spectrometry Based Approach

The Emerging Therapeutic Potential of Nitro Fatty Acids and Other Michael Acceptor-Containing Drugs for the Treatment of Inflammation and Cancer

Croton tiglium essential oil compounds have anti-proliferative and pro-apoptotic effects in A549 lung cancer cell lines

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