Abstract
BackgroundClinacanthus 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.MethodsWe 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.ResultsAll 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.ConclusionThese 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.
Highlights
Clinacanthus nutans extracts have been consumed by the cancer patients with the hope that the extracts can kill cancers more effectively than conventional chemotherapies
Hii et al BMC Complementary and Alternative Medicine (2019) 19:257 (Continued from previous page). These results provide strong evidence of C. nutans extracts being inefficacious as monotherapy for cancer
C. nutans extracts selectively inhibit proliferation of human pancreatic ductal adenocarcinoma To evaluate whether C. nutans extracts exhibited anti-proliferative effects, a total of 23 human cancer cells (MCF7, MDA-MB-231, MDA-MB-468, HCC38, HCT116, HT29, SW48, Caco2, A549, NCI-H1299, NCI-H23, Calu-1, AN3CA, HEC-1-A, HEC-1-B, RL95–2, CNE1, HK1, SUNE1, TWO1, AsPC1, BxPC3 and SW1990) were treated with 1-100 μg/mL of Polar leaf extracts of Clinacanthus nutans (LP), Non-polar leaf extracts of Clinacanthus nutans (LN), Polar stem extracts of Clinacanthus nutans (SP) or Non-polar stem extracts of Clinacanthus nutans (SN) for 72 h
Summary
Clinacanthus nutans extracts have been consumed by the cancer patients with the hope that the extracts can kill cancers more effectively than conventional chemotherapies. Many cancer patients use therapies promoted as viable alternatives to conventional cancer treatment with questionable outcomes Such unproven modalities can be potentially harmful. An even greater proportion of cancer patients use complementary therapies such as herbs and supplements along with conventional cancer treatment such as chemotherapy and radiation therapy. Some of these may have been proven to be adjunctive approaches that control symptoms and enhance quality of life. The drug-herb interaction effects of such complementary therapies with chemotherapy agents are often not studied during clinical trials or even receive post-marketing surveillance [1, 2]. Despite dietary or plant-isolated compounds [6,7,8,9,10,11,12] exhibiting a potent anticancer effect, thorough scientific investigation should be conducted in order to validate their effects on cancer treatment
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