Back to Search
Start Over
The synergism of Clinacanthus nutans Lindau extracts with gemcitabine: downregulation of anti-apoptotic markers in squamous pancreatic ductal adenocarcinoma.
- Source :
- BMC Complementary & Alternative Medicine; 9/14/2019, Vol. 19 Issue 1, pN.PAG-N.PAG, 1p, 3 Charts, 3 Graphs
- Publication Year :
- 2019
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- BREAST tumor prevention
RECTUM tumors
TUMOR prevention
COLON tumor prevention
CELL proliferation
ANTIMETABOLITES
APOPTOSIS
BIOMARKERS
BIOLOGICAL assay
CALCIUM-binding proteins
CANCER chemotherapy
CELL lines
COMBINATION drug therapy
COLORIMETRY
DRUG synergism
ENZYME-linked immunosorbent assay
GENE expression
IMMUNOBLOTTING
LUNG tumors
MEDICINAL plants
NASOPHARYNX tumors
ONCOGENES
PANCREATIC tumors
PROBABILITY theory
SQUAMOUS cell carcinoma
STATISTICS
PLANT extracts
ENDOMETRIAL tumors
DATA analysis
DUCTAL carcinoma
PROTEIN microarrays
TOLL-like receptors
SIGNAL peptides
ONE-way analysis of variance
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 14726882
- Volume :
- 19
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- BMC Complementary & Alternative Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 138631403
- Full Text :
- https://doi.org/10.1186/s12906-019-2663-9