Grape seed procyanidin extract (GSE) has been shown to exert antineoplastic properties in preclinical studies. Recently, we reported findings from a modified phase I, open-label, dose escalation clinical study conducted to evaluate the safety, tolerability, MTD, and potential chemopreventive effects of leucoselect phytosome, a standardized GSE complexed with soy phospholipids to enhance bioavailability, in heavy active and former smokers. Three months of leucoselect phytosome treatment significantly decreased bronchial Ki-67 labeling index (LI), a marker of cell proliferation on the bronchial epithelium. Because GSE is widely used as a supplement to support cardiovascular health, we evaluate the impact of oral leucoselect phytosome on the fasting serum complex lipid metabolomics profiles in our participants. One month of leucoselect phytosome treatment significantly increased eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the omega-3 polyunsaturated fatty acids (n-3 PUFA) with well-established anticancer properties. Leucoselect phytosome also significantly increased unsaturated phosphatidylcholines (PC), likely from soy phospolipids in the phytosome and functioning as transporters for these PUFAs. Furthermore, 3-month leucoselect phytosome treatment significantly increased serum prostaglandin (PG) E3 (PGE3), a metabolite of EPA with anti-inflammatory and antineoplastic properties. Such increases in PGE3 correlated with reductions of bronchial Ki-67 LI ( r = −0.9; P = 0.0374). Moreover, posttreatment plasma samples from trial participants significantly inhibited proliferation of human lung cancer cell lines A549 (adenocarcinoma), H520 (squamous cell carcinoma), DMS114 (small cell carcinoma), and 1198 (preneoplastic cell line). Our findings further support the potential utility of leucoselect phytosome in reducing cardiovascular and neoplastic risks in heavy former and active smokers. Prevention Relevance: In this correlative study of leucoselect phytosome for lung cancer chemoprevention in heavy active and former smokers, we demonstrate for the first time, favorable modulations of n-3PUFA and downstream PGE3 in fasting serum, further supporting the chemopreventive potential of leucoselect phytosome against lung cancer.

中文翻译：

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Leucoselect Phytosome 在 I 期肺癌化学预防研究中调节血清二十碳五烯酸、二十二碳六烯酸和前列腺素 E3

在临床前研究中，葡萄籽原花青素提取物 (GSE) 已被证明具有抗肿瘤特性。最近，我们报告了一项改进的 I 期、开放标签、剂量递增临床研究的结果，该研究旨在评估 leucoselect phytosome 的安全性、耐受性、MTD 和潜在的化学预防作用，leucoselect phytosome 是一种与大豆磷脂复合以提高生物利用度的标准化 GSE，在重活跃的和曾经的吸烟者。三个月的 leucoselect phytosome 治疗显着降低了支气管 Ki-67 标记指数 (LI)，这是支气管上皮细胞增殖的标志物。由于 GSE 被广泛用作支持心血管健康的补充剂，因此我们评估了口服 leucoselect phytosome 对参与者空腹血清复杂脂质代谢组学特征的影响。一个月的 leucoselect phytosome 治疗显着增加了二十碳五烯酸 (EPA) 和二十二碳六烯酸 (DHA)，这是一种具有公认的抗癌特性的 omega-3 多不饱和脂肪酸 (n-3 PUFA)。Leucoselect phytosome 还显着增加了不饱和磷脂酰胆碱 (PC)，可能来自植物体内的大豆磷脂，并作为这些 PUFA 的转运蛋白发挥作用。此外，3 个月的 leucoselect phytosome 治疗显着增加了血清前列腺素 (PG) E3 (PGE3)，这是一种具有抗炎和抗肿瘤特性的 EPA 代谢物。PGE3 的这种增加与支气管 Ki-67 LI 的减少相关（r = -0.9；P = 0.0374）。此外，来自试验参与者的治疗后血浆样本显着抑制人肺癌细胞系 A549（腺癌）的增殖，H520（鳞状细胞癌）、DMS114（小细胞癌）和 1198（癌前细胞系）。我们的研究结果进一步支持了 leucoselect phytosome 在降低重度前吸烟者和活跃吸烟者心血管和肿瘤风险方面的潜在效用。预防相关性：在这项 leucoselect phytosome 对重度吸烟者和前吸烟者肺癌化学预防的相关研究中，我们首次证明了空腹血清中 n-3PUFA 和下游 PGE3 的有利调节，进一步支持了 leucoselect phytosome 的化学预防潜力肺癌。