Russo Veronica, Oliva Maria Antonietta, Ricchiuti Rossella, Alborghetti Marika, Arcella Antonietta
IRCCS Istituto Neurologico Mediterraneo NEUROMED, Via Atinense 18, 86077, Pozzilli, Italy.
Department of Neuroscience, Mental Health and Sensory Organ (NESMOS), and Department of Neuroscience, Sapenza University of Rome, Rome, Italy, Via di Grottarossa, 1035/1039, 00189.
Clin Transl Oncol. 2025 May 21. doi: 10.1007/s12094-025-03931-z.
Petit grain (PGO), a citrus essential oil (EO), isolated from the twigs and leaves of bitter orange (citrus arantiun), has been shown to have different beneficial properties, such as antibacterial, anti-fungal, anti-viral, anti-inflammatory and anti-cancer properties. Hypopharyngeal carcinoma is typically treated with combination radiotherapy and chemotherapy (cisplatin). However, resistance to cisplatin may lead to other new treatments, such as immunotherapy, which can be well-tolerated and potentially beneficial.
In this study, PGO was proposed as a natural growth-regulating molecule of the FaDu cell line from hypopharyngeal squamous cell carcinoma.
The study used MTT assay, growth curves, Western blot, and FACS analysis to assess the impact of PGO on petit grain cell growth, protein levels, and cell cycle phases.
The potent cytotoxic effect of PGO against FaDu was demonstrated by its low IC50. Daily administration of 0.025% (v/v) and 0.5% (v/v) PGO on FaDu cells resulted in a time and dose-dependent decrease in cell viability and growth. PGO caused a cell cycle arrest in the G1/S transition phase, which was verified by increased expression of cell cycle regulating proteins p27, p21 and p18, and a decrease of CDK2 and CDK4 proteins. PGO treatment also reduced the phosphorylation of the proliferative signals pAKT. Last but not least, PGO dramatically increased the sensitivity of FaDu cells to chemotherapy when combined with cis-platin, the usual treatment for squamous cell carcinoma.
Since PGO inhibits the growth of FaDu squamous carcinoma cells through a variety of combined mechanisms, it could be considered as a promising adjuvant therapy for this complex disease.
苦橙叶油（PGO）是一种从苦橙（柑橘属）的嫩枝和叶子中分离出来的柑橘属植物精油，已被证明具有多种有益特性，如抗菌、抗真菌、抗病毒、抗炎和抗癌特性。下咽癌通常采用放疗和化疗（顺铂）联合治疗。然而，对顺铂的耐药性可能会导致其他新的治疗方法，如免疫疗法，这种疗法耐受性良好且可能有益。
在本研究中，PGO被提议作为下咽鳞状细胞癌FaDu细胞系的一种天然生长调节分子。
该研究使用MTT法、生长曲线、蛋白质免疫印迹法和流式细胞术分析来评估PGO对苦橙叶油细胞生长、蛋白质水平和细胞周期阶段的影响。
PGO对FaDu具有强大的细胞毒性作用，其半数抑制浓度（IC50）较低。每天对FaDu细胞施用0.025%（v/v）和0.5%（v/v）的PGO会导致细胞活力和生长呈时间和剂量依赖性下降。PGO导致细胞周期在G1/S转换期停滞，这通过细胞周期调节蛋白p27、p21和p18表达增加以及细胞周期蛋白依赖性激酶2（CDK2）和细胞周期蛋白依赖性激酶4（CDK4）蛋白减少得到证实。PGO处理还降低了增殖信号pAKT的磷酸化水平。最后但同样重要的是，当与鳞状细胞癌的常用治疗药物顺铂联合使用时，PGO显著提高了FaDu细胞对化疗的敏感性。
由于PGO通过多种联合机制抑制FaDu鳞状癌细胞的生长，它可被视为这种复杂疾病有前景的辅助治疗方法。
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