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- Title
The synergism of Clinacanthus nutans Lindau extracts with gemcitabine: downregulation of anti-apoptotic markers in squamous pancreatic ductal adenocarcinoma.
- Authors
Hii, Ling-Wei; Lim, Swee-Hua Erin; Leong, Chee-Onn; Chin, Swee-Yee; Tan, Ngai-Paing; Lai, Kok-Song; Mai, Chun-Wai
- 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.
- 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
- Publication
BMC Complementary & Alternative Medicine, 2019, Vol 19, Issue 1, pN.PAG
- ISSN
1472-6882
- Publication type
Academic Journal
- DOI
10.1186/s12906-019-2663-9