Center for Disease Prevention Research, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.
Department of Pharmacology & Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.
Cell Commun Signal. 2020 Apr 7;18(1):58. doi: 10.1186/s12964-020-0524-2.
Magnolia extract (ME) is known to inhibit cancer growth and metastasis in several cell types in vitro and in animal models. However, there is no detailed study on the preventive efficacy of ME for oral cancer, and the key components in ME and their exact mechanisms of action are not clear. The overall goal of this study is to characterize ME preclinically as a potent oral cancer chemopreventive agent and to determine the key components and their molecular mechanism(s) that underlie its chemopreventive efficacy.
The antitumor efficacy of ME in oral cancer was investigated in a 4-nitroquinoline-1-oxide (4NQO)-induced mouse model and in two oral cancer orthotopic models. The effects of ME on mitochondrial electron transport chain activity and ROS production in mouse oral tumors was also investigated.
ME did not cause detectable side effects indicating that it is a promising and safe chemopreventive agent for oral cancer. Three major key active compounds in ME (honokiol, magnolol and 4-O-methylhonokiol) contribute to its chemopreventive effects. ME inhibits mitochondrial respiration at complex I of the electron transport chain, oxidizes peroxiredoxins, activates AMPK, and inhibits STAT3 phosphorylation, resulting in inhibition of the growth and proliferation of oral cancer cells.
Our data using highly relevant preclinical oral cancer models, which share histopathological features seen in human oral carcinogenesis, suggest a novel signaling and regulatory role for mitochondria-generated superoxide and hydrogen peroxide in suppressing oral cancer cell proliferation, progression, and metastasis. Video abstract.
厚朴提取物（ME）已被证实可抑制多种细胞类型的体外和动物模型中的癌症生长和转移。然而，目前尚缺乏关于 ME 预防口腔癌的详细研究，并且 ME 中的关键成分及其确切作用机制尚不清楚。本研究的总体目标是将 ME 作为一种有效的口腔癌化学预防剂进行临床前研究，并确定其化学预防功效的关键成分及其分子机制。
采用 4-硝基喹啉-1-氧化物（4NQO）诱导的小鼠模型和两种口腔癌原位模型研究 ME 对口腔癌的抗肿瘤作用。还研究了 ME 对小鼠口腔肿瘤中线粒体电子传递链活性和 ROS 产生的影响。
ME 未引起可检测的副作用，表明其是一种有前途且安全的口腔癌化学预防剂。ME 中的三种主要活性成分（厚朴酚、和厚朴酚和 4-O-甲基厚朴酚）对其化学预防作用有贡献。ME 抑制电子传递链复合体 I 中的线粒体呼吸，氧化过氧化物酶，激活 AMPK，并抑制 STAT3 磷酸化，从而抑制口腔癌细胞的生长和增殖。
我们使用与人类口腔癌发生具有组织病理学特征的高度相关的临床前口腔癌模型的数据表明，线粒体产生的超氧阴离子和过氧化氢在抑制口腔癌细胞增殖、进展和转移方面具有新的信号和调节作用。视频摘要。
