Berberine inhibits carcinogenesis through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in a mouse hepatoma model
Chemoprevention of hepatocellular carcinoma (HCC) is highly desirable in clinic. Berberine (BBR) is reported to play potential roles in cancer treatment and prevention. We studied the chemopreventive effect of BBR on hepatocellular carcinogenesis in an inflammation-driven mouse model, as it was enri...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-09-01
|
| Series: | Molecular Therapy: Oncolytics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770522001000 |
| _version_ | 1817995597364330496 |
|---|---|
| author | Gang Ren Jiang-Hong Guo Chen-Lin Feng Yu-Wei Ding Biao Dong Yan-Xing Han Yu-Huan Li Lu-Lu Wang Jian-Dong Jiang |
| author_facet | Gang Ren Jiang-Hong Guo Chen-Lin Feng Yu-Wei Ding Biao Dong Yan-Xing Han Yu-Huan Li Lu-Lu Wang Jian-Dong Jiang |
| author_sort | Gang Ren |
| collection | DOAJ |
| description | Chemoprevention of hepatocellular carcinoma (HCC) is highly desirable in clinic. Berberine (BBR) is reported to play potential roles in cancer treatment and prevention. We studied the chemopreventive effect of BBR on hepatocellular carcinogenesis in an inflammation-driven mouse model, as it was enriched in liver after oral administration. Oral BBR significantly decreased the number and volume of visible nodular tumors, and prolonged the median overall survival by 9 and 8 weeks in the diethylnitrosamine (DEN)-injected male and female mice respectively. The nodular tumors were induced through activation of the lysophosphatidic acid (LPA) pathway in liver. LPA stimulated the abnormal leptin transcription through interacting with LPA receptor-2 (LPAR2) followed by p38 activation, and BBR inhibited carcinogenesis by suppressing the bioactivity of LPA. Specifically, BBR significantly reduced the expression of the LPA synthetase autotaxin (ATX) and LPAR2 in the nodular tumors of DEN-injected mice. Subsequently, BBR repressed the abnormal transcription of leptin stimulated by LPA-induced phosphorylation of p38 in hepatoma cells. In fact, BBR reduced the abnormal expression of leptin in livers of DEN-injected male mice throughout the course of an 8-month experiment. BBR might be a preventive agent for HCC, working at least partially through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in liver. |
| first_indexed | 2024-04-14T02:08:39Z |
| format | Article |
| id | doaj.art-eed9698a1e754c0293010ad3f19ecc32 |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-04-14T02:08:39Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-eed9698a1e754c0293010ad3f19ecc322022-12-22T02:18:34ZengElsevierMolecular Therapy: Oncolytics2372-77052022-09-0126372386Berberine inhibits carcinogenesis through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in a mouse hepatoma modelGang Ren0Jiang-Hong Guo1Chen-Lin Feng2Yu-Wei Ding3Biao Dong4Yan-Xing Han5Yu-Huan Li6Lu-Lu Wang7Jian-Dong Jiang8Department of Virology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Tian Tan Xi Li, Dongcheng District, Beijing 100050, China; Corresponding author Gang Ren, Ph.D. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Tian Tan Xi Li, Dongcheng District Beijing 100050, China.State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Xicheng District, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Xicheng District, Beijing 100050, ChinaDepartment of Virology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Tian Tan Xi Li, Dongcheng District, Beijing 100050, ChinaDepartment of Virology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Tian Tan Xi Li, Dongcheng District, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Xicheng District, Beijing 100050, ChinaDepartment of Virology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Tian Tan Xi Li, Dongcheng District, Beijing 100050, ChinaDepartment of Virology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Tian Tan Xi Li, Dongcheng District, Beijing 100050, China; Corresponding author Lu-Lu Wang, Ph.D., Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Tian Tan Xi Li, Dongcheng District, Beijing 100050, China.Department of Virology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Tian Tan Xi Li, Dongcheng District, Beijing 100050, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Xicheng District, Beijing 100050, China; Corresponding author Jian-Dong Jiang, M.D. Institute of Medicinal Biotechnology and Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Tian Tan Xi Li, Dongcheng District, Beijing 100050, China.Chemoprevention of hepatocellular carcinoma (HCC) is highly desirable in clinic. Berberine (BBR) is reported to play potential roles in cancer treatment and prevention. We studied the chemopreventive effect of BBR on hepatocellular carcinogenesis in an inflammation-driven mouse model, as it was enriched in liver after oral administration. Oral BBR significantly decreased the number and volume of visible nodular tumors, and prolonged the median overall survival by 9 and 8 weeks in the diethylnitrosamine (DEN)-injected male and female mice respectively. The nodular tumors were induced through activation of the lysophosphatidic acid (LPA) pathway in liver. LPA stimulated the abnormal leptin transcription through interacting with LPA receptor-2 (LPAR2) followed by p38 activation, and BBR inhibited carcinogenesis by suppressing the bioactivity of LPA. Specifically, BBR significantly reduced the expression of the LPA synthetase autotaxin (ATX) and LPAR2 in the nodular tumors of DEN-injected mice. Subsequently, BBR repressed the abnormal transcription of leptin stimulated by LPA-induced phosphorylation of p38 in hepatoma cells. In fact, BBR reduced the abnormal expression of leptin in livers of DEN-injected male mice throughout the course of an 8-month experiment. BBR might be a preventive agent for HCC, working at least partially through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in liver.http://www.sciencedirect.com/science/article/pii/S2372770522001000hepatocellular carcinomaberberineLPA receptor-2autotaxinleptin |
| spellingShingle | Gang Ren Jiang-Hong Guo Chen-Lin Feng Yu-Wei Ding Biao Dong Yan-Xing Han Yu-Huan Li Lu-Lu Wang Jian-Dong Jiang Berberine inhibits carcinogenesis through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in a mouse hepatoma model Molecular Therapy: Oncolytics hepatocellular carcinoma berberine LPA receptor-2 autotaxin leptin |
| title | Berberine inhibits carcinogenesis through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in a mouse hepatoma model |
| title_full | Berberine inhibits carcinogenesis through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in a mouse hepatoma model |
| title_fullStr | Berberine inhibits carcinogenesis through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in a mouse hepatoma model |
| title_full_unstemmed | Berberine inhibits carcinogenesis through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in a mouse hepatoma model |
| title_short | Berberine inhibits carcinogenesis through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in a mouse hepatoma model |
| title_sort | berberine inhibits carcinogenesis through antagonizing the atx lpa lpar2 p38 leptin axis in a mouse hepatoma model |
| topic | hepatocellular carcinoma berberine LPA receptor-2 autotaxin leptin |
| url | http://www.sciencedirect.com/science/article/pii/S2372770522001000 |
| work_keys_str_mv | AT gangren berberineinhibitscarcinogenesisthroughantagonizingtheatxlpalpar2p38leptinaxisinamousehepatomamodel AT jianghongguo berberineinhibitscarcinogenesisthroughantagonizingtheatxlpalpar2p38leptinaxisinamousehepatomamodel AT chenlinfeng berberineinhibitscarcinogenesisthroughantagonizingtheatxlpalpar2p38leptinaxisinamousehepatomamodel AT yuweiding berberineinhibitscarcinogenesisthroughantagonizingtheatxlpalpar2p38leptinaxisinamousehepatomamodel AT biaodong berberineinhibitscarcinogenesisthroughantagonizingtheatxlpalpar2p38leptinaxisinamousehepatomamodel AT yanxinghan berberineinhibitscarcinogenesisthroughantagonizingtheatxlpalpar2p38leptinaxisinamousehepatomamodel AT yuhuanli berberineinhibitscarcinogenesisthroughantagonizingtheatxlpalpar2p38leptinaxisinamousehepatomamodel AT luluwang berberineinhibitscarcinogenesisthroughantagonizingtheatxlpalpar2p38leptinaxisinamousehepatomamodel AT jiandongjiang berberineinhibitscarcinogenesisthroughantagonizingtheatxlpalpar2p38leptinaxisinamousehepatomamodel |