Fulvic acid exhibits antitumor effects in ovarian cancer cells by upregulating cytochrome P450 family 1 subfamily A member 1 expression

Abstract Objective Fulvic acid (FA), a humic substance, has various applications in agricultural (animal husbandry) and pharmaceutical industries. However, to the best of our knowledge, its antitumor effects remain unclear. This study aimed to elucidate the effects and underlying mechanisms of FA in...

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Main Authors: Min Chen, Ming Cheng, Chenchen Shao, Wenwen Liang, Yi Tang, Fangjun Ding
Format: Article
Language:English
Published: Springer 2025-04-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02236-5
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author Min Chen
Ming Cheng
Chenchen Shao
Wenwen Liang
Yi Tang
Fangjun Ding
author_facet Min Chen
Ming Cheng
Chenchen Shao
Wenwen Liang
Yi Tang
Fangjun Ding
author_sort Min Chen
collection DOAJ
description Abstract Objective Fulvic acid (FA), a humic substance, has various applications in agricultural (animal husbandry) and pharmaceutical industries. However, to the best of our knowledge, its antitumor effects remain unclear. This study aimed to elucidate the effects and underlying mechanisms of FA in ovarian cancer cells. Methods To determine the half-maximal inhibitory concentration (IC50) of FA, SK-OV-3 and OVCAR3 ovarian cancer cells were exposed to various concentrations of FA. The effects of FA and expression of cytochrome P450 family 1 subfamily A member 1 (CYP1A1) on cellular proliferation, migration, and invasion were evaluated using the Cell Counting Kit-8 and transwell assays for migration and invasion. Differentially expressed messenger ribonucleic acids (mRNAs) were identified via Illumina ribonucleic acid (RNA) sequencing and verified using fluorescent quantitative reverse transcription polymerase chain reaction (qRT-PCR). CYP1A1 protein levels were measured by western blotting. Results The IC50 values of FA for OVCAR3 and SK-OV-3 cells were 689.9 and 752.0 µg/ml, respectively. FA treatment suppressed cell proliferation, invasion, and migration. In FA-treated SK-OV-3 cells, 117 mRNAs were upregulated, and 342 mRNAs were downregulated, as identified by Illumina RNA sequencing. The qRT-PCR results revealed that FA upregulated CYP1A1 expression in both cell lines. CYP1A1 overexpression mimicked the effects of FA treatment on cell proliferation, invasion, and migration. Furthermore, CYP1A1 knockdown alleviated these effects induced by FA treatments. Conclusion FA suppressed cell proliferation, invasion, and migration and upregulated CYP1A1 expression in SK-OV-3 and OVCAR3 cells. Our results suggest that FA demonstrates antitumor effects in ovarian cancer cells through CYP1A1 regulation.
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spelling doaj-art-ad9fa0f0fc0c467e866a9fa8492188fe2025-08-20T02:11:42ZengSpringerDiscover Oncology2730-60112025-04-0116111310.1007/s12672-025-02236-5Fulvic acid exhibits antitumor effects in ovarian cancer cells by upregulating cytochrome P450 family 1 subfamily A member 1 expressionMin Chen0Ming Cheng1Chenchen Shao2Wenwen Liang3Yi Tang4Fangjun Ding5Shandong Agricultural University Fertilizer Science & Technology Co., LtdDepartment of Gastrointestinal Surgery, The Affiliated Tai’an City Central Hospital of Qingdao UniversityDepartment of Obstetrics and Gynecology, The Affiliated Tai’an City Central Hospital of Qingdao UniversityDepartment of Obstetrics and Gynecology, The Affiliated Tai’an City Central Hospital of Qingdao UniversityCollege of Animal Science and Technology, Shandong Agricultural UniversityShandong Agricultural University Fertilizer Science & Technology Co., LtdAbstract Objective Fulvic acid (FA), a humic substance, has various applications in agricultural (animal husbandry) and pharmaceutical industries. However, to the best of our knowledge, its antitumor effects remain unclear. This study aimed to elucidate the effects and underlying mechanisms of FA in ovarian cancer cells. Methods To determine the half-maximal inhibitory concentration (IC50) of FA, SK-OV-3 and OVCAR3 ovarian cancer cells were exposed to various concentrations of FA. The effects of FA and expression of cytochrome P450 family 1 subfamily A member 1 (CYP1A1) on cellular proliferation, migration, and invasion were evaluated using the Cell Counting Kit-8 and transwell assays for migration and invasion. Differentially expressed messenger ribonucleic acids (mRNAs) were identified via Illumina ribonucleic acid (RNA) sequencing and verified using fluorescent quantitative reverse transcription polymerase chain reaction (qRT-PCR). CYP1A1 protein levels were measured by western blotting. Results The IC50 values of FA for OVCAR3 and SK-OV-3 cells were 689.9 and 752.0 µg/ml, respectively. FA treatment suppressed cell proliferation, invasion, and migration. In FA-treated SK-OV-3 cells, 117 mRNAs were upregulated, and 342 mRNAs were downregulated, as identified by Illumina RNA sequencing. The qRT-PCR results revealed that FA upregulated CYP1A1 expression in both cell lines. CYP1A1 overexpression mimicked the effects of FA treatment on cell proliferation, invasion, and migration. Furthermore, CYP1A1 knockdown alleviated these effects induced by FA treatments. Conclusion FA suppressed cell proliferation, invasion, and migration and upregulated CYP1A1 expression in SK-OV-3 and OVCAR3 cells. Our results suggest that FA demonstrates antitumor effects in ovarian cancer cells through CYP1A1 regulation.https://doi.org/10.1007/s12672-025-02236-5Fulvic acidOvarian cancerCytochrome P450 CYP1A1RNA sequencing
spellingShingle Min Chen
Ming Cheng
Chenchen Shao
Wenwen Liang
Yi Tang
Fangjun Ding
Fulvic acid exhibits antitumor effects in ovarian cancer cells by upregulating cytochrome P450 family 1 subfamily A member 1 expression
Discover Oncology
Fulvic acid
Ovarian cancer
Cytochrome P450 CYP1A1
RNA sequencing
title Fulvic acid exhibits antitumor effects in ovarian cancer cells by upregulating cytochrome P450 family 1 subfamily A member 1 expression
title_full Fulvic acid exhibits antitumor effects in ovarian cancer cells by upregulating cytochrome P450 family 1 subfamily A member 1 expression
title_fullStr Fulvic acid exhibits antitumor effects in ovarian cancer cells by upregulating cytochrome P450 family 1 subfamily A member 1 expression
title_full_unstemmed Fulvic acid exhibits antitumor effects in ovarian cancer cells by upregulating cytochrome P450 family 1 subfamily A member 1 expression
title_short Fulvic acid exhibits antitumor effects in ovarian cancer cells by upregulating cytochrome P450 family 1 subfamily A member 1 expression
title_sort fulvic acid exhibits antitumor effects in ovarian cancer cells by upregulating cytochrome p450 family 1 subfamily a member 1 expression
topic Fulvic acid
Ovarian cancer
Cytochrome P450 CYP1A1
RNA sequencing
url https://doi.org/10.1007/s12672-025-02236-5
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