Citrus reticulatapeel oil inhibits non-small cell lung cancer cell proliferation in culture and implanted in nude mice

Abstract

Non-small cell lung cancer (NSCLC) accounts for most cases of lung cancer. The peel oil of mandarin Citrus reticulata Blanco cv. Dancy (MPO) is a natural source of essential oils and carotenoids. Volatile and non-volatile lipid compounds were characterized by chromatographic methods. We demonstrate that MPO causes a dose-dependent growth inhibition of NSCLC model cells (A549) in culture and tumour growth in vivo of the same cells implanted in nude mice fed with MPO-supplemented diets. MPO induced cell cycle arrest mainly at the G0/G1 phase and reduced the amount of membrane-bound Ras protein along with apoptosis induction. No toxicological effect was found in liver parameters analysed in treated mice and histopathological analyses of their organs did not show any morphological changes. In conclusion, the data suggest that MPO possesses significant antitumor activity without causing systemic toxicity, proposing it as a dietary supplement that may be helpful in cancer prevention.

Safety and efficacy of a feed additive consisting of expressed mandarin oil from the fruit peels of Citrus reticulata Blanco for use in all animal species (FEFANA asbl)

“…17 Non-volatile predominantly constituents include polymethoxylated flavones (PMF), e.g. tangeretin (0.2-0.5%), nobiletin (0.07-0.25%) and heptamethoxyflavone (0.05-0.15%), (ranges based on Verzera et al, 1997;Feger et al, 2003;Schipilliti et al, 2010;Dugo and Russo, 2010), and carotenoid esters (0.03-0.42%, as reported by Giuffrida et al, 2006 andCastro et al, 2018), mainly b-cryptoxanthin and its laurate, myristate and palmitate esters (Giuffrida et al, 2006;Zerlotti Mercadante et al, 2017).…”

Bioactive Compounds of Citrus Fruits: A Review of Composition and Health Benefits of Carotenoids, Flavonoids, Limonoids, and Terpenes

“…The peel oil of mandarin, rich in limonene, myrcene, and carotenoids, has led to the dose-dependent growth inhibition of A549 non-small-cell lung cancer (NSCLC) cells and tumor growth in nude mice implemented with A479 cells [ 115 ]. In this study, supplementation of 5.25 mg/d of peel oil per mouse for seven days significantly decreased tumor growth by reducing the expression of membrane-bound Ras protein, increasing apoptosis, and inducing cell cycle arrest at the G0/G1 phase.…”

Anti-cancer mechanisms of linalool and 1,8-cineole in non-small cell lung cancer A549 cells

“…A549 cells (6 Â 10 5 ) were seeded in 100 mm Petri dishes and allowed to attach 24 h before being treated with ethanol 0.2% (control), linalool 2.0 mM, 1.8-cineole 8.0 mM, or DMSO 5% for 48 h. Then, the cells were rinsed twice with PBS and lysed in RIPA lysis buffer [(50 mM Tris-HCl -pH 8.0, 150 mM NaCl, 1.0% (v/v) NP-40, 0.5% (w/v) sodium deoxycholate, 0.1% SDS, and 1 mM EDTA)] supplemented with protease inhibitors (Thermo Fisher Scientific, USA; Cat. #A32963) for 30 min on ice and centrifuged 15 min at 14,000 Â g at 4 C. The protein content was quantified by the method of Bradford [31]. Protein samples (50 μg) were subjected to Western Blot according to standard procedures previously reported [16].…”