Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.
J Food Sci. 2022 Jul;87(7):3307-3317. doi: 10.1111/1750-3841.16228. Epub 2022 Jun 16.
Ginger extract (GE) and its major component 6-gingerol (6G) have been reported to exert anti-tumor effects in various cancers. The underlying mechanism, however, has not been well demonstrated. Here, we have focused on the relationship between promotion of mitochondrial biogenesis in tumor infiltrating CD8 T cells induced by GE and 6G and their cytotoxic effect. The results showed that GE induced 56% inhibition of tumor growth in Lewis lung carcinoma (LLC) xenograft mouse model and 6G induced 33% (25 mg/kg) and 37% (50 mg/kg) inhibition. GE increased mitochondrial mass of CD8 T cells in tumor and draining lymph nodes (DLNs) significantly, while 6G had no significant effect. GE and 6G both had no significant influence on histopathological changes of liver and kidney in mice. In the co-culture system of CTLL-2 cells and LLC cells, GE enhanced the cytotoxicity of CTLL-2 cells against LLC cells by 14% and 19% at concentrations of 2.5 and 5 mg/ml, respectively. 6G did not promote cytotoxicity of CTLL-2 cells. GE increased mitochondrial mass at 5 and 10 mg/ml and mtDNA copy number and ATP production at 2.5, 5, 10 mg/ml in CTLL-2 cells. 6G promoted mtDNA copy number at 50, 100, 150 µM and mitochondrial mass and ATP production at 25, 50, 100, 150 µM in CTLL-2 cells. These results suggest that promotion of mitochondrial biogenesis and function in tumor infiltrating CD8 T cells may play an essential role in GE-induced inhibition of tumor growth. The current results perfect the mechanism of anti-tumor effect of ginger, which is beneficial for further application in cancer management. PRACTICAL APPLICATION: Ginger, as a worldwide food seasoning and herbal medicine in traditional Chinese medicine, has been reported to possess anti-tumor efficacy. To our knowledge, it is the first time to focus on ginger's ability of promoting mitochondrial biogenesis in tumor infiltrating CD8 T cells to explore the mechanism of its anti-tumor effect. Our observations demonstrate that ginger inhibits tumor growth via promoting mitochondrial biogenesis and function of T cells. The present study links food to anti-tumor immunity and provides impetus to investigate and design dietary supplements for cancer management.
姜提取物（GE）及其主要成分 6-姜酚（6G）已被报道在各种癌症中具有抗肿瘤作用。然而，其潜在机制尚未得到很好的证明。在这里，我们专注于 GE 和 6G 诱导肿瘤浸润 CD8 T 细胞中线粒体生物发生的促进与它们的细胞毒性作用之间的关系。结果表明，GE 在 Lewis 肺癌（LLC）异种移植小鼠模型中诱导了 56%的肿瘤生长抑制，而 6G 诱导了 33%（25mg/kg）和 37%（50mg/kg）的抑制。GE 显著增加了肿瘤和引流淋巴结（DLN）中 CD8 T 细胞的线粒体质量，而 6G 则没有显著影响。GE 和 6G 对小鼠的肝和肾组织病理学变化均无显著影响。在 CTLL-2 细胞和 LLC 细胞的共培养系统中，GE 在浓度为 2.5 和 5mg/ml 时分别增强了 CTLL-2 细胞对 LLC 细胞的细胞毒性 14%和 19%。6G 并没有促进 CTLL-2 细胞的细胞毒性。GE 在 5 和 10mg/ml 时增加了线粒体质量，在 2.5、5、10mg/ml 时增加了 mtDNA 拷贝数和 ATP 产生。6G 在 50、100、150µM 时促进了 mtDNA 拷贝数，在 25、50、100、150µM 时促进了线粒体质量和 ATP 产生。这些结果表明，促进肿瘤浸润 CD8 T 细胞中线粒体生物发生和功能可能在 GE 诱导的肿瘤生长抑制中发挥重要作用。目前的结果完善了姜的抗肿瘤作用机制，这有利于进一步应用于癌症管理。实际应用：生姜作为一种世界范围内的食品调味料和中草药，已被报道具有抗肿瘤功效。据我们所知，这是首次关注生姜促进肿瘤浸润 CD8 T 细胞中线粒体生物发生的能力，以探索其抗肿瘤作用的机制。我们的观察表明，生姜通过促进 T 细胞的线粒体生物发生和功能来抑制肿瘤生长。本研究将食物与抗肿瘤免疫联系起来，为研究和设计癌症管理的膳食补充剂提供了动力。
