Stilbene B10 induces apoptosis and tumor suppression in lymphoid Raji cells by BTK-mediated regulation of the KRAS/HDAC1/EP300/PEBP1 axis
Lymphoma is a cancer of the lymphoid cells that originated in matured B or T cells. The bioactive natural compounds can efficiently treat this disease with lesser side effects. Thus, in this study, a natural stilbene B10 (3-methoxy 5-hydroxy stilbene) isolated from Cajanus cajan (Pigeon Pea) was scr...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222012768 |
| _version_ | 1798018888625029120 |
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| author | Krishnapriya M. Varier Gou Dan Wuling Liu Guoping Wu Chaoda Xiao Huang Lei Tao Ling Yanping Jiang Ying Chen Yaacov Ben-David Yanmei Li Nenling Zhang Babu Gajendran Xiangchun Shen |
| author_facet | Krishnapriya M. Varier Gou Dan Wuling Liu Guoping Wu Chaoda Xiao Huang Lei Tao Ling Yanping Jiang Ying Chen Yaacov Ben-David Yanmei Li Nenling Zhang Babu Gajendran Xiangchun Shen |
| author_sort | Krishnapriya M. Varier |
| collection | DOAJ |
| description | Lymphoma is a cancer of the lymphoid cells that originated in matured B or T cells. The bioactive natural compounds can efficiently treat this disease with lesser side effects. Thus, in this study, a natural stilbene B10 (3-methoxy 5-hydroxy stilbene) isolated from Cajanus cajan (Pigeon Pea) was screened for its anti-proliferative efficacy against 13 cancer cell lines. B10 showed a potential effect on the human lymphoma (Raji) cells. Cytotoxicity analysis of B10 has revealed IC50 concentrations in Raji cells at low doses (18 µM) than other cancer cell lines. The B10 could significantly cause dose and time-dependent inhibition in the proliferation of Raji cells triggering intrinsic apoptosis and S/G1 phase cellular arrest. There was an increased expression of phospho-γ-H2A.X and decreased expression of cyclin D1, causing DNA damage and cell cycle arrest, post- B10 treatments. The mitochondrial membrane potential (MMP) variations observed after B10 treatment led to changes in Bax/Bcl-2 ratio, cytochrome C release, and enhanced expression of cleaved caspase3, 9, PARP-1, and APAF-1. The B10 inhibited the proliferation of Raji cells by significantly downregulating the expression of KRAS, BTK, MDM2, P-JAK2, P-STAT3, PI3K, HDAC1/2, SIRT7, and EP300. The treatment upregulated the tumor suppressor genes PEBP1 and SAP18. Thus, the study could reveal the selective inhibitory effects of B10 on lymphoma, suggesting it as a probable innovative chemotherapeutic agent. |
| first_indexed | 2024-04-11T16:31:38Z |
| format | Article |
| id | doaj.art-95d556a840b84286b9fbbfc72f973ba9 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-11T16:31:38Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-95d556a840b84286b9fbbfc72f973ba92022-12-22T04:14:01ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-12-01156113887Stilbene B10 induces apoptosis and tumor suppression in lymphoid Raji cells by BTK-mediated regulation of the KRAS/HDAC1/EP300/PEBP1 axisKrishnapriya M. Varier0Gou Dan1Wuling Liu2Guoping Wu3Chaoda Xiao4Huang Lei5Tao Ling6Yanping Jiang7Ying Chen8Yaacov Ben-David9Yanmei Li10Nenling Zhang11Babu Gajendran12Xiangchun Shen13School of Pharmaceutical Sciences/State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang 550014, PR ChinaSchool of Pharmaceutical Sciences/State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, PR ChinaSchool of Pharmaceutical Sciences/State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang 550014, PR ChinaSchool of Pharmaceutical Sciences/State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, PR ChinaSchool of Pharmaceutical Sciences/State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, PR ChinaSchool of Pharmaceutical Sciences/State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang 550014, PR ChinaSchool of Pharmaceutical Sciences/State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, PR ChinaDepartment of Dermatology, The Affiliated Hospital of Guizhou Medical University, Guiyang, PR ChinaSchool of Pharmaceutical Sciences/State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, PR ChinaSchool of Pharmaceutical Sciences/State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang 550014, PR ChinaSchool of Pharmaceutical Sciences/State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang 550014, PR China; Corresponding authors at: School of Pharmaceutical Sciences/State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, PR China.School of Pharmaceutical Sciences/State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, PR China; Corresponding author.School of Pharmaceutical Sciences/State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang 550014, PR China; Corresponding authors at: School of Pharmaceutical Sciences/State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, PR China.School of Pharmaceutical Sciences/State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang 550014, PR China; Corresponding authors at: School of Pharmaceutical Sciences/State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, PR China.Lymphoma is a cancer of the lymphoid cells that originated in matured B or T cells. The bioactive natural compounds can efficiently treat this disease with lesser side effects. Thus, in this study, a natural stilbene B10 (3-methoxy 5-hydroxy stilbene) isolated from Cajanus cajan (Pigeon Pea) was screened for its anti-proliferative efficacy against 13 cancer cell lines. B10 showed a potential effect on the human lymphoma (Raji) cells. Cytotoxicity analysis of B10 has revealed IC50 concentrations in Raji cells at low doses (18 µM) than other cancer cell lines. The B10 could significantly cause dose and time-dependent inhibition in the proliferation of Raji cells triggering intrinsic apoptosis and S/G1 phase cellular arrest. There was an increased expression of phospho-γ-H2A.X and decreased expression of cyclin D1, causing DNA damage and cell cycle arrest, post- B10 treatments. The mitochondrial membrane potential (MMP) variations observed after B10 treatment led to changes in Bax/Bcl-2 ratio, cytochrome C release, and enhanced expression of cleaved caspase3, 9, PARP-1, and APAF-1. The B10 inhibited the proliferation of Raji cells by significantly downregulating the expression of KRAS, BTK, MDM2, P-JAK2, P-STAT3, PI3K, HDAC1/2, SIRT7, and EP300. The treatment upregulated the tumor suppressor genes PEBP1 and SAP18. Thus, the study could reveal the selective inhibitory effects of B10 on lymphoma, suggesting it as a probable innovative chemotherapeutic agent.http://www.sciencedirect.com/science/article/pii/S0753332222012768BTKEP300LymphomaPEBP1RajiStilbenes |
| spellingShingle | Krishnapriya M. Varier Gou Dan Wuling Liu Guoping Wu Chaoda Xiao Huang Lei Tao Ling Yanping Jiang Ying Chen Yaacov Ben-David Yanmei Li Nenling Zhang Babu Gajendran Xiangchun Shen Stilbene B10 induces apoptosis and tumor suppression in lymphoid Raji cells by BTK-mediated regulation of the KRAS/HDAC1/EP300/PEBP1 axis Biomedicine & Pharmacotherapy BTK EP300 Lymphoma PEBP1 Raji Stilbenes |
| title | Stilbene B10 induces apoptosis and tumor suppression in lymphoid Raji cells by BTK-mediated regulation of the KRAS/HDAC1/EP300/PEBP1 axis |
| title_full | Stilbene B10 induces apoptosis and tumor suppression in lymphoid Raji cells by BTK-mediated regulation of the KRAS/HDAC1/EP300/PEBP1 axis |
| title_fullStr | Stilbene B10 induces apoptosis and tumor suppression in lymphoid Raji cells by BTK-mediated regulation of the KRAS/HDAC1/EP300/PEBP1 axis |
| title_full_unstemmed | Stilbene B10 induces apoptosis and tumor suppression in lymphoid Raji cells by BTK-mediated regulation of the KRAS/HDAC1/EP300/PEBP1 axis |
| title_short | Stilbene B10 induces apoptosis and tumor suppression in lymphoid Raji cells by BTK-mediated regulation of the KRAS/HDAC1/EP300/PEBP1 axis |
| title_sort | stilbene b10 induces apoptosis and tumor suppression in lymphoid raji cells by btk mediated regulation of the kras hdac1 ep300 pebp1 axis |
| topic | BTK EP300 Lymphoma PEBP1 Raji Stilbenes |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222012768 |
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