The synergism of Clinacanthus nutans Lindau extracts with gemcitabine: downregulation of anti-apoptotic markers in squamous pancreatic ductal adenocarcinoma
Abstract Background Clinacanthus nutans extracts have been consumed by the cancer patients with the hope that the extracts can kill cancers more effectively than conventional chemotherapies. Our previous study reported its anti-inflammatory effects were caused by inhibiting Toll-like Receptor-4 (TLR...
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| Format: | Article |
| Language: | English |
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BMC
2019-09-01
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| Series: | BMC Complementary and Alternative Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s12906-019-2663-9 |
| _version_ | 1819055692983566336 |
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| author | Ling-Wei Hii Swee-Hua Erin Lim Chee-Onn Leong Swee-Yee Chin Ngai-Paing Tan Kok-Song Lai Chun-Wai Mai |
| author_facet | Ling-Wei Hii Swee-Hua Erin Lim Chee-Onn Leong Swee-Yee Chin Ngai-Paing Tan Kok-Song Lai Chun-Wai Mai |
| author_sort | Ling-Wei Hii |
| collection | DOAJ |
| description | Abstract Background Clinacanthus nutans extracts have been consumed by the cancer patients with the hope that the extracts can kill cancers more effectively than conventional chemotherapies. Our previous study reported its anti-inflammatory effects were caused by inhibiting Toll-like Receptor-4 (TLR-4) activation. However, we are unsure of its anticancer effect, and its interaction with existing chemotherapy. Methods We investigated the anti-proliferative efficacy of polar leaf extracts (LP), non-polar leaf extracts (LN), polar stem extract (SP) and non-polar stem extracts (SN) in human breast, colorectal, lung, endometrial, nasopharyngeal, and pancreatic cancer cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT assay. The most potent extracts was tested along with gemcitabine using our established drug combination analysis. The effect of the combinatory treatment in apoptosis were quantified using enzyme-linked immunosorbent assay (ELISA), Annexin V assay, antibody array and immunoblotting. Statistical significance was analysed using one-way analysis of variance (ANOVA) and post hoc Dunnett’s test. A p-value of less than 0.05 (p < 0.05) was considered statistical significance. Results All extracts tested were not able to induce potent anti-proliferative effects. However, it was found that pancreatic ductal adenocarcinoma, PDAC (AsPC1, BxPC3 and SW1990) were the cell lines most sensitive cell lines to SN extracts. This is the first report of C. nutans SN extracts acting in synergy with gemcitabine, the first line chemotherapy for pancreatic cancer, as compared to conventional monotherapy. In the presence of SN extracts, we can reduce the dose of gemcitabine 2.38–5.28 folds but still maintain the effects of gemcitabine in PDAC. SN extracts potentiated the killing of gemcitabine in PDAC by apoptosis. Bax was upregulated while bcl-2, cIAP-2, and XIAP levels were downregulated in SW1990 and BxPC3 cells treated with gemcitabine and SN extracts. The synergism was independent of TLR-4 expression in pancreatic cancer cells. Conclusion These results provide strong evidence of C. nutans extracts being inefficacious as monotherapy for cancer. Hence, it should not be used as a total substitution for any chemotherapy agents. However, SN extracts may synergise with gemcitabine in the anti-tumor mechanism. |
| first_indexed | 2024-12-21T13:11:34Z |
| format | Article |
| id | doaj.art-f16972e005df40e48d15800f3832dafa |
| institution | Directory Open Access Journal |
| issn | 1472-6882 |
| language | English |
| last_indexed | 2024-12-21T13:11:34Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
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| series | BMC Complementary and Alternative Medicine |
| spelling | doaj.art-f16972e005df40e48d15800f3832dafa2022-12-21T19:02:52ZengBMCBMC Complementary and Alternative Medicine1472-68822019-09-0119111310.1186/s12906-019-2663-9The synergism of Clinacanthus nutans Lindau extracts with gemcitabine: downregulation of anti-apoptotic markers in squamous pancreatic ductal adenocarcinomaLing-Wei Hii0Swee-Hua Erin Lim1Chee-Onn Leong2Swee-Yee Chin3Ngai-Paing Tan4Kok-Song Lai5Chun-Wai Mai6Department of Life Sciences, School of Pharmacy, International Medical UniversityPerdana University-Royal College of Surgeons in IrelandDepartment of Life Sciences, School of Pharmacy, International Medical UniversityDepartment of Pharmaceutical Chemistry, School of Pharmacy, International Medical UniversityDepartment of Land Management, Faculty of Agriculture, Universiti Putra MalaysiaHealth Sciences Division, Abu Dhabi Women’s College, Higher Colleges of TechnologyCentre for Cancer and Stem Cells Research, Institute for Research Development and Innovation, International Medical UniversityAbstract Background Clinacanthus nutans extracts have been consumed by the cancer patients with the hope that the extracts can kill cancers more effectively than conventional chemotherapies. Our previous study reported its anti-inflammatory effects were caused by inhibiting Toll-like Receptor-4 (TLR-4) activation. However, we are unsure of its anticancer effect, and its interaction with existing chemotherapy. Methods We investigated the anti-proliferative efficacy of polar leaf extracts (LP), non-polar leaf extracts (LN), polar stem extract (SP) and non-polar stem extracts (SN) in human breast, colorectal, lung, endometrial, nasopharyngeal, and pancreatic cancer cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT assay. The most potent extracts was tested along with gemcitabine using our established drug combination analysis. The effect of the combinatory treatment in apoptosis were quantified using enzyme-linked immunosorbent assay (ELISA), Annexin V assay, antibody array and immunoblotting. Statistical significance was analysed using one-way analysis of variance (ANOVA) and post hoc Dunnett’s test. A p-value of less than 0.05 (p < 0.05) was considered statistical significance. Results All extracts tested were not able to induce potent anti-proliferative effects. However, it was found that pancreatic ductal adenocarcinoma, PDAC (AsPC1, BxPC3 and SW1990) were the cell lines most sensitive cell lines to SN extracts. This is the first report of C. nutans SN extracts acting in synergy with gemcitabine, the first line chemotherapy for pancreatic cancer, as compared to conventional monotherapy. In the presence of SN extracts, we can reduce the dose of gemcitabine 2.38–5.28 folds but still maintain the effects of gemcitabine in PDAC. SN extracts potentiated the killing of gemcitabine in PDAC by apoptosis. Bax was upregulated while bcl-2, cIAP-2, and XIAP levels were downregulated in SW1990 and BxPC3 cells treated with gemcitabine and SN extracts. The synergism was independent of TLR-4 expression in pancreatic cancer cells. Conclusion These results provide strong evidence of C. nutans extracts being inefficacious as monotherapy for cancer. Hence, it should not be used as a total substitution for any chemotherapy agents. However, SN extracts may synergise with gemcitabine in the anti-tumor mechanism.http://link.springer.com/article/10.1186/s12906-019-2663-9Clinacanthus nutansSynergismPancreatic ductal adenocarcinomaGemcitabine |
| spellingShingle | Ling-Wei Hii Swee-Hua Erin Lim Chee-Onn Leong Swee-Yee Chin Ngai-Paing Tan Kok-Song Lai Chun-Wai Mai The synergism of Clinacanthus nutans Lindau extracts with gemcitabine: downregulation of anti-apoptotic markers in squamous pancreatic ductal adenocarcinoma BMC Complementary and Alternative Medicine Clinacanthus nutans Synergism Pancreatic ductal adenocarcinoma Gemcitabine |
| title | The synergism of Clinacanthus nutans Lindau extracts with gemcitabine: downregulation of anti-apoptotic markers in squamous pancreatic ductal adenocarcinoma |
| title_full | The synergism of Clinacanthus nutans Lindau extracts with gemcitabine: downregulation of anti-apoptotic markers in squamous pancreatic ductal adenocarcinoma |
| title_fullStr | The synergism of Clinacanthus nutans Lindau extracts with gemcitabine: downregulation of anti-apoptotic markers in squamous pancreatic ductal adenocarcinoma |
| title_full_unstemmed | The synergism of Clinacanthus nutans Lindau extracts with gemcitabine: downregulation of anti-apoptotic markers in squamous pancreatic ductal adenocarcinoma |
| title_short | The synergism of Clinacanthus nutans Lindau extracts with gemcitabine: downregulation of anti-apoptotic markers in squamous pancreatic ductal adenocarcinoma |
| title_sort | synergism of clinacanthus nutans lindau extracts with gemcitabine downregulation of anti apoptotic markers in squamous pancreatic ductal adenocarcinoma |
| topic | Clinacanthus nutans Synergism Pancreatic ductal adenocarcinoma Gemcitabine |
| url | http://link.springer.com/article/10.1186/s12906-019-2663-9 |
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