Rapid discovery of a novel “green” and natural GST inhibitor for sensitizing hepatocellular carcinoma to Cisplatin by visual screening strategy

Linxi Mao; Yan Qin; Jialong Fan; Wei Yang; Bin Li; Liang Cao; Liqin Yuan; Mengyun Wang; Bin Liu; Wei Wang

doi:10.1016/j.jpha.2023.12.013

Volume 14 Issue 5

May 2024

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Article Navigation > Journal of Pharmaceutical Analysis > 2024 > 14(5): 100923

Linxi Mao, Yan Qin, Jialong Fan, Wei Yang, Bin Li, Liang Cao, Liqin Yuan, Mengyun Wang, Bin Liu, Wei Wang. Rapid discovery of a novel “green” and natural GST inhibitor for sensitizing hepatocellular carcinoma to Cisplatin by visual screening strategy[J]. Journal of Pharmaceutical Analysis, 2024, 14(5): 100923. doi: 10.1016/j.jpha.2023.12.013

Citation:

Linxi Mao, Yan Qin, Jialong Fan, Wei Yang, Bin Li, Liang Cao, Liqin Yuan, Mengyun Wang, Bin Liu, Wei Wang. Rapid discovery of a novel “green” and natural GST inhibitor for sensitizing hepatocellular carcinoma to Cisplatin by visual screening strategy[J]. Journal of Pharmaceutical Analysis, 2024, 14(5): 100923. doi: 10.1016/j.jpha.2023.12.013

Citation:

Linxi Mao, Yan Qin, Jialong Fan, Wei Yang, Bin Li, Liang Cao, Liqin Yuan, Mengyun Wang, Bin Liu, Wei Wang. Rapid discovery of a novel “green” and natural GST inhibitor for sensitizing hepatocellular carcinoma to Cisplatin by visual screening strategy[J]. Journal of Pharmaceutical Analysis, 2024, 14(5): 100923. doi: 10.1016/j.jpha.2023.12.013

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Rapid discovery of a novel “green” and natural GST inhibitor for sensitizing hepatocellular carcinoma to Cisplatin by visual screening strategy

doi: 10.1016/j.jpha.2023.12.013

Linxi Mao^a,
Yan Qin^{a,b
,
,},
Jialong Fan^b,
Wei Yang^c,
Bin Li^a
,,
Liang Cao^a,
Liqin Yuan^d,
Mengyun Wang^a,
Bin Liu^{b
,
,},
Wei Wang^{a
,
,}

a. TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China;
b. College of Biology, Hunan University, Changsha, 410082, China;
c. College of Foreign Languages, Hunan Women's University, Changsha, 410004, China;
d. Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, China

Funds:

This work was supported by the National Natural Science Foundation of China (Grant Nos.: 82003931, 82204766 and 81374062), the Outstanding Youth Foundation of Hunan Provincial Education Department of China (Grant No.: 20B445), the Hunan Youth Science and Technology Innovation Talents Project, China (Grant No.: 2021RC3100), the Chinese Postdoctoral Science foundation (Grant No.: 2021M690974), Changjiang Scholars Program in Ministry Education, People's Republic of China (Program No.: T2019133), and the Scientific Research Project of Hunan Provincial Education Department (Project No.: 21B0394).

Received Date: Aug. 27, 2023
Accepted Date: Dec. 16, 2023
Rev Recd Date: Nov. 24, 2023
Publish Date: May 30, 2024

Abstract

Abstract

Over-expression of glutathione S-transferase (GST) can promote Cisplatin resistance in hepatocellular carcinoma (HCC) treatment. Hence, inhibiting GST is an attractive strategy to improve Cisplatin sensitivity in HCC therapy. Although several synthesized GST inhibitors have been developed, the side effects and narrow spectrum for anticancer seriously limit their clinical application. Considering the abundance of natural compounds with anticancer activity, this study developed a rapid fluorescence technique to screen “green” natural GST inhibitors with high specificity. The fluorescence assay demonstrated that schisanlactone B (hereafter abbreviated as C1) isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo. Importantly, C1 can selectively kill HCC cells from normal liver cells, effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression. Considering the high GST levels in HCC patients, this compound demonstrated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.
- GST,
- Drug resistance,
- Fluorescence,
- Hepatocarcinoma,
- Natural compound C1,
- “Green” GST inhibitor

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References(35)

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