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一种甲醇提取物增强阿霉素对耐药结直肠癌细胞的体外细胞毒性。

A Methanol Extract of Enhances Doxorubicin Cytotoxicity against Resistant Colorectal Cancer Cells In Vitro.

机构信息

Unit of Bioactive Natural Substances and Biotechnology UR17ES47, Faculty of Dental Medicine of Monastir, University of Monastir, Avicenne Street, 5000 Monastir, Tunisia.

Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.

出版信息

Molecules. 2020 Nov 12;25(22):5265. doi: 10.3390/molecules25225265.

DOI:10.3390/molecules25225265
PMID:33198146
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7697796/
Abstract

Colorectal cancer is a malignancy with a high incidence. Currently, the drugs used in chemotherapy are often accompanied by strong side effects. Natural secondary metabolites can interfere with chemotherapeutic drugs and intensify their cytotoxic effects. This study aimed to profile the secondary metabolites from the methanol extract of and investigate their in vitro activities, alone or in combination with the chemotherapeutic agent doxorubicin. MTT assay was used to determine the cytotoxic activities. Annexin-V/PI double-staining analysis was employed to evaluate the apoptotic concentration. Multicaspase assay, quantitative reverse transcription real-time PCR (RT-qPCR), and ABC transporter activities were also performed. LC-MS analysis revealed 31 compounds including phenolic acids, flavonoids, and saponins. extract intensified doxorubicin anti-proliferative effects against resistant tumor cells and enhanced the cytotoxic effects towards Caco-2 cells after 48 h. The mRNA expression levels of Bax, caspase-3, and p21 were increased significantly whereas Bcl-2 expression level was decreased. Furthermore, the methanol extract reversed P-glycoprotein or multidrug resistance-associated protein in Caco-2 cells. In conclusion, improved chemosensitivity and modulated multidrug resistance in Caco-2 cells which makes it a good candidate for further research in order to develop a new potential cancer treatment.

摘要

结直肠癌是一种发病率较高的恶性肿瘤。目前，化疗中使用的药物常伴有较强的副作用。天然次生代谢物可以干扰化疗药物，并增强其细胞毒性作用。本研究旨在对 的甲醇提取物中的次生代谢产物进行分析，并研究其单独或与化疗药物阿霉素联合的体外活性。MTT 法用于测定细胞毒性活性。采用 Annexin-V/PI 双重染色分析评估凋亡浓度。还进行了多半胱氨酸酶测定、定量逆转录实时 PCR（RT-qPCR）和 ABC 转运体活性测定。LC-MS 分析显示 31 种化合物，包括酚酸、黄酮类和皂苷。 提取物增强了多柔比星对耐药肿瘤细胞的增殖抑制作用，并在 48 小时后增强了对 Caco-2 细胞的细胞毒性作用。Bax、caspase-3 和 p21 的 mRNA 表达水平显著增加，而 Bcl-2 的表达水平降低。此外，甲醇提取物还可逆转 Caco-2 细胞中的 P-糖蛋白或多药耐药相关蛋白。总之， 提高了结直肠癌细胞的化疗敏感性并调节了多药耐药性，使其成为进一步研究开发新的潜在癌症治疗方法的良好候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0581/7697796/e59bd1f3c432/molecules-25-05265-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0581/7697796/75152fecca5a/molecules-25-05265-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0581/7697796/42efad126c77/molecules-25-05265-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0581/7697796/f78d20090f7f/molecules-25-05265-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0581/7697796/f41fd86ffb46/molecules-25-05265-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0581/7697796/cad7fcff4b43/molecules-25-05265-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0581/7697796/0a2e09792c5d/molecules-25-05265-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0581/7697796/e59bd1f3c432/molecules-25-05265-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0581/7697796/75152fecca5a/molecules-25-05265-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0581/7697796/42efad126c77/molecules-25-05265-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0581/7697796/f78d20090f7f/molecules-25-05265-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0581/7697796/f41fd86ffb46/molecules-25-05265-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0581/7697796/cad7fcff4b43/molecules-25-05265-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0581/7697796/0a2e09792c5d/molecules-25-05265-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0581/7697796/e59bd1f3c432/molecules-25-05265-g007.jpg

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