Evaluate the inhibition of cytochrome P450 1A1 for enhancing breast cancer chemotherapy with a turn-on fluorescent probe

Evaluate the inhibition of cytochrome P450 1A1 for enhancing breast cancer chemotherapy with a turn-on fluorescent probe
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DOI:
10.1016/j.snb.2021.130233
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发表时间:
2021-10
影响因子:
8.4
通讯作者:
Yan Huang;Lei Yu;Pengpeng Lu;Ying-Ting Wei;Xiaoyan Wang;Lingxin Chen
Yan Huang;Lei Yu;Pengpeng Lu;Ying-Ting Wei;Xiaoyan Wang;Lingxin Chen
中科院分区:
化学1区
文献类型:
--
作者:
Yan Huang;Lei Yu;Pengpeng Lu;Ying-Ting Wei;Xiaoyan Wang;Lingxin Chen

文献摘要

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乳腺癌发病率居世界女性恶性肿瘤之首,死亡率高。早期诊断和治疗是降低乳腺癌死亡率的重要途径。迫切需要证据明确、疗效可靠的抗肿瘤策略。由于细胞色素P450 1A1 (CYP1A1)在乳腺癌中普遍表达,并且具有出色的代谢外源药物的能力,因此研究CYP1A1在乳腺癌中的重要功能引起了研究人员的兴趣。在这里,我们报道了一种bby - cyp荧光探针,用于细胞和体内CYP1A1的成像。与其他生物分子相比,该探针对CYP1A1的检测具有突出的选择性和高灵敏度。我们的研究结果表明,MCF-7和MDA-MB-231细胞内CYP1A1水平升高,鼠油醇抑制CYP1A1可有效诱导两种乳腺癌细胞凋亡。因此,CYP1A1在乳腺癌中起着至关重要的作用。在荷瘤小鼠中,鼠油醇与化疗药物的协同作用优于单独化疗药物。CYP1A1水平可能成为乳腺癌早期诊断的新的生物标志物。
The incidence rate of breast cancer ranks first in women malignant tumors worldwide, accompanied by a high mortality. The early diagnosis and therapy are important way to reduce the mortality rate of breast cancer in clinical practice. There are urgent needs for anti-tumor strategies with clear evidence and reliable efficacy. Because cytochrome P450 1A1 (CYP1A1) is commonly expressed in breast cancer and has the excellent ability to metabolize xenobiotics, researchers are interested in studying the vital function of CYP1A1 in breast cancer. Herein, we report a BCy-CYP fluorescent probe for imaging of CYP1A1 in cells and in vivo. This probe has outstanding selectivity and high sensitivity for CYP1A1 detection over other biomolecules. Our results reveal that the intracellular CYP1A1 level increase in MCF-7 and MDA-MB-231 cells, and inhibition of CYP1A1 by carnosol efficiently induce apoptosis in the two kinds of breast cancer cells. Thus, CYP1A1 plays a crucial role in breast cancer. The synergistic effect of carnosol and chemotherapy drug is better than chemotherapy drug alone in tumor-bearing mice. CYP1A1 level may be a new biomarker for breast cancer early diagnosis.