Evidence map›Paper›PMID 31521140›Full record

ArticleBMC complementary and alternative medicine2019

The synergism of Clinacanthus nutans Lindau extracts with gemcitabine: downregulation of anti-apoptotic markers in squamous pancreatic ductal adenocarcinoma.

Ling-Wei Hii, Swee-Hua Erin Lim, Chee-Onn Leong, Swee-Yee Chin, Ngai-Paing Tan, Kok-Song Lai, Chun-Wai Mai

Open access · goldAbstract read
In one paragraph

Article in BMC complementary and alternative medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
5.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 29 citations in OpenAlex.

  1. Frontiers in pharmacology · 2026
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  3. The ethyl acetate extract ofSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024
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  4. Medicina (Kaunas, Lithuania) · 2023
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  5. Vitamin E in the management of pancreatic cancer: A scoping review.World journal of gastrointestinal oncology · 2023
    Article
  6. Review
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  8. Review
  9. Article
  10. Recent Advancement in Anticancer Activity ofEvidence-based complementary and alternative medicine : eCAM · 2021
    Review
  11. Article
  12. Review
  13. Review
  14. Enhanced cytotoxic effects ofJournal of advanced pharmaceutical technology & research
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 3 countries.

Ling-Wei HiiDepartment of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur, 57000, Malaysia.
Swee-Hua Erin LimPerdana University-Royal College of Surgeons in Ireland, Seri Kembangan, 43400, Selangor, Malaysia.
Chee-Onn LeongDepartment of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur, 57000, Malaysia.
Swee-Yee ChinDepartment of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 57000, Kuala Lumpur, Malaysia.
Ngai-Paing TanDepartment of Land Management, Faculty of Agriculture, Universiti Putra Malaysia, Seri Kembangan, 43400, Selangor, Malaysia.
Kok-Song LaiHealth Sciences Division, Abu Dhabi Women's College, Higher Colleges of Technology, Abu Dhabi, United Arab Emirates. laikoksong@gmail.com.
Chun-Wai MaiCentre for Cancer and Stem Cells Research, Institute for Research Development and Innovation, International Medical University, Kuala Lumpur, 57000, Malaysia. mai.chunwai@gmail.com.ORCID http://orcid.org/0000-0001-6532-184X
Higher Colleges of Technology · AEIMU University · MYInstitute for Medical Research · MYUniversiti Putra Malaysia · MY

Funding

International Medical University BP-I-01-2018(13)
6 · The paper itself

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.

Indexed as

AcanthaceaeAntineoplastic AgentsApoptosisBaculoviral IAP Repeat-Containing 3 ProteinCarcinoma, Squamous CellCell Line, TumorCell ProliferationDeoxycytidineDrug SynergismGemcitabineHumansPancreatic NeoplasmsPlant ExtractsProto-Oncogene Proteins c-bcl-2Antineoplastic AgentsBaculoviral IAP Repeat-Containing 3 ProteinBIRC3 protein, humanDeoxycytidineGemcitabinePlant ExtractsProto-Oncogene Proteins c-bcl-2Clinacanthus nutansGemcitabinePancreatic ductal adenocarcinomaSynergism

Identifiers

PMID31521140
PMCPMC6744713
OpenAlexW2972869453

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.