Oral cancer is the 16th most common malignant tumor worldwide. The risk of recurrence and mortality is high, and the survival rate is low over the following five years. Recent studies have shown that curcumin causes apoptosis in tumor cells by affecting FoF1-ATP synthase (ATP synthase) activity, which, in turn, hinders cell energy production, leading to a loss of cell viability. Additionally, irradiation of curcumin within cells can intensify its detrimental effects on cancer cell viability and proliferation (photodynamic therapy). We treated the OHSU-974 cell line, a model for human head and neck squamous cell carcinoma (HNSCC), and primary human fibroblasts. The treatment involved a 1 h exposure of cells to 0.1, 1.0, and 10 μM curcumin, followed or not by irradiation or the addition of the same concentration of pre-irradiated curcumin. Both instances involved a diode laser with a wavelength of 450 nm (0.25 W, 15 J, 60 s, 1 cm2, continuous wave mode). The treatment with non-irradiated 1 and 10 µM curcumin caused ATP synthase inhibition and a consequent reduction in the oxygen consumption rate (OCR) and the ATP/AMP ratio, which was associated with a decrement in lipid peroxidation accumulation and a slight increase in glutathione reductase and catalase activity. By contrast, 60 s curcumin irradiation with 0.25 W—450 nm caused a further oxidative phosphorylation (OxPhos) metabolism impairment that induced an uncoupling between respiration and energy production, leading to increased oxidative damage, a cellular growth and viability reduction, and a cell cycle block in the G1 phase. These effects appeared to be more evident when the curcumin was irradiated after cell incubation. Since cells belonging to the HNSCC microenvironment support tumor development, curcumin’s effects have been analyzed on primary human fibroblasts, and a decrease in cell energy status has been observed with both irradiated and non-irradiated curcumin and an increase in oxidative lipid damage and a slowing of cell growth were observed when the curcumin was irradiated before or after cellular administration. Thus, although curcumin displays an anti-cancer role on OHSU-974 in its native form, photoactivation seems to enhance its effects, making it effective even at low dosages.
口腔癌是全球第16位最常见的恶性肿瘤，其复发和死亡风险高，五年生存率低。近期研究表明，姜黄素通过影响FoF1-ATP合酶活性诱导肿瘤细胞凋亡，进而阻碍细胞能量生成，导致细胞活力丧失。此外，细胞内姜黄素的光照可增强其对癌细胞活力和增殖的抑制作用（光动力疗法）。本研究以人头颈鳞状细胞癌模型细胞系OHSU-974及原代人成纤维细胞为对象，分别用0.1、1.0和10 μM姜黄素处理1小时，后续进行或不进行光照处理，或添加等浓度预辐照姜黄素。光照处理均采用波长450 nm的二极管激光器（功率0.25 W，能量15 J，照射60 s，光斑面积1 cm²，连续波模式）。实验发现：未经光照的1和10 µM姜黄素处理可抑制ATP合酶活性，导致耗氧率和ATP/AMP比值下降，同时伴随脂质过氧化积累减少以及谷胱甘肽还原酶和过氧化氢酶活性轻微升高。相比之下，经0.25 W-450 nm激光照射60秒的姜黄素会进一步损害氧化磷酸化代谢，引起呼吸作用与能量生成解耦联，导致氧化损伤加剧、细胞生长与活力下降以及G1期细胞周期阻滞。当姜黄素在细胞孵育后进行光照时，这些效应更为显著。鉴于头颈鳞癌微环境中的细胞支持肿瘤发展，本研究同时分析了姜黄素对原代人成纤维细胞的影响：无论是否光照，姜黄素均能降低细胞能量状态；而光照处理（无论给药前后进行）均会加剧氧化性脂质损伤并延缓细胞生长。因此，虽然天然形态的姜黄素对OHSU-974细胞已显示抗癌作用，但光活化能进一步增强其效应，使其在低剂量下仍能发挥显著效果。
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