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陈酿黑蒜提取物通过 ROS-JNK 通路下调 MCL-1 表达抑制雌激素受体阳性乳腺癌细胞的生长。

Aged black garlic extract inhibits the growth of estrogen receptor-positive breast cancer cells by downregulating MCL-1 expression through the ROS-JNK pathway.

机构信息

Inner Mongolia Medical University Third Clinical Medical College, Inner Mongolia Autonomous Region, Baotou, China.

Department of Experimental Center, The Third Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia Autonomous Region, Baotou, China.

出版信息

PLoS One. 2023 Jun 23;18(6):e0286454. doi: 10.1371/journal.pone.0286454. eCollection 2023.

DOI:10.1371/journal.pone.0286454
PMID:37352173
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10289325/
Abstract

The black garlic is produced from the raw garlic by Milliard reaction at high temperature (60-90°C) and humidity (70-90%). In this process, the pungent odor and gastrointestinal irritation effects of the raw garlic are reduced. At the same time, unstable compounds such as allicin are converted into stable organosulfur compounds with antioxidant activity. Previous studies have confirmed that black garlic extract has anti-tumor effects and could inhibit the proliferation of various tumor cells, including breast cancer cells MCF-7. However, the mechanisms of the anti-tumor effects remain unclear. In this study, we found that the black garlic extract could inhibit the proliferation, invasion, and metastasis of estrogen receptor-positive breast cancer cells, promote their apoptosis, and inhibit their epithelial-mesenchymal transition. Mechanistically, the black garlic extract reduced the expression of the anti-apoptotic protein MCL-1, which was achieved by modulating the ROS-JNK signaling pathway. In addition, the black garlic extract also decreased the expression of BCL-2 and increased the expression of BAX and BIM. We also found that the black garlic extract, in combination with venetoclax, a BCL-2 inhibitor, synergistically kills the estrogen receptor-positive breast cancer cells. These results suggested that black garlic extract has great therapeutic value and prospects for estrogen receptor-positive breast cancer treatment.

摘要

黑蒜是通过高温(60-90°C)和高湿度(70-90%)下的美拉德反应由生蒜制成的。在这个过程中,生蒜的刺鼻气味和胃肠道刺激性得到了降低。同时,不稳定的化合物如蒜素转化为具有抗氧化活性的稳定有机硫化合物。先前的研究已经证实,黑蒜提取物具有抗肿瘤作用,可以抑制多种肿瘤细胞的增殖,包括乳腺癌细胞 MCF-7。然而,其抗肿瘤作用的机制尚不清楚。在这项研究中,我们发现黑蒜提取物可以抑制雌激素受体阳性乳腺癌细胞的增殖、侵袭和转移,促进其凋亡,并抑制其上皮-间充质转化。在机制上,黑蒜提取物通过调节 ROS-JNK 信号通路降低了抗凋亡蛋白 MCL-1 的表达。此外,黑蒜提取物还降低了 BCL-2 的表达,增加了 BAX 和 BIM 的表达。我们还发现,黑蒜提取物与 BCL-2 抑制剂 venetoclax 联合使用,可以协同杀死雌激素受体阳性乳腺癌细胞。这些结果表明,黑蒜提取物具有很大的治疗价值和治疗雌激素受体阳性乳腺癌的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4ab/10289325/1da4c94f509d/pone.0286454.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4ab/10289325/a113a45362e5/pone.0286454.g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4ab/10289325/1da4c94f509d/pone.0286454.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4ab/10289325/a113a45362e5/pone.0286454.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4ab/10289325/baa782b0a83d/pone.0286454.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4ab/10289325/ddc897ed3cbb/pone.0286454.g003.jpg
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