Evidence map›Paper›PMID 33526051›Full record

ArticleChinese medicine2021

Shikonin promotes ubiquitination and degradation of cIAP1/2-mediated apoptosis and necrosis in triple negative breast cancer cells.

Anqi Wang, Jiayu Liu, Yuhan Yang, Zhejie Chen, Caifang Gao, Zhanguo Wang, Chaomei Fu, Liang Zou, Shengpeng Wang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chinese medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
4.0field-weighted citation impact, top 5% 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

11 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Traditional Chinese Medicine for Breast Cancer: A Review.Breast cancer (Dove Medical Press) · 2023
    Review
  8. Promising Nanomedicines of Shikonin for Cancer Therapy.International journal of nanomedicine · 2023
    Review
  9. Article
  10. Article
  11. Review
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

9 authors at 4 institutions in 3 countries.

Anqi Wang *School of medicine, Chengdu University, Chengdu, 610106, China.
Jiayu Liu *Clinical drug development, School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Yuhan YangState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Zhejie ChenState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Caifang GaoState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Zhanguo WangSchool of medicine, Chengdu University, Chengdu, 610106, China.
Chaomei FuSchool of Pharmacy, State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Chengdu University of Traditional Chinese Medicine, 611137, Chengdu, China.
Liang ZouKey Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Chengdu University, 610106, Chengdu, China. zouliang@cdu.edu.cn.
Shengpeng WangState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. swang@um.edu.mo.ORCID http://orcid.org/0000-0002-8997-456X
University of Macau · MOChengdu University · CNChengdu University of Traditional Chinese Medicine · CNQueen Mary University of London · GB

Funding

Key-Area Research and Development Program of Guangdong Province 2020B1111110003Science and Technology Development Fund, Macau SAR 0013/2019/AFJ and SKL-QRCM(UM)-2020-2022University of Macau MYRG2019-00143-ICMS
6 · The paper itself

Abstract

backgroundShikonin (SKO) is a natural naphthoquinone derived from Chinese herbal medicine Arnebiae Radix with high development potentials due to its anti-inflammatory and anti-tumor activities. Overwhelming evidences have indicated that SKO can induce both necrosis and apoptosis in cancer cells, while the mechanisms for triple negative breast cancer cells is still need to be disclosed.

methodsIn this study, kinds of molecular biological technologies, including flow-cytometry, Western blot, immunoprecipitation, enzyme-linked immunosorbent assay (ELISA) as well as real-time quantitative PCR (RT-qPCR), were applied for investigation on the underlying mechanisms of SKO induced necrosis and apoptosis for MDA-MB-231 cells. Inhibitors were also used for validation ofthe key signaling pathways involved in SKO triggered necrosis and apoptosis.

resultsWe found that SKO significantly triggered necrosis and apoptosis of MDA-MB-231 cells in both a concentration- and time-dependent manner. Mechanism studies demonstrated that SKO significantly promoted the autoubiquitination levels and facilitated the proteasome dependent degradation of cellular inhibitor of apoptosis protein 1 (cIAP1) and cIAP2 in MDA-MB-231 cells. Autoubiquitination and degradation of cIAP1 and cIAP2 induced by SKO further led to significant decreased ubiquitination and inactivation of RIP1, which played an important role in inhibition of pro-survival and accelerating of necrosis of MDA-MB-231 cells. Treatment with proteasome inhibitor lactacystin significantly rescued the cell viability induced by treatment of SKO.

conclusionsOur results demonstrate that SKO promotes the autoubiquitination and degradation of cIAP1 and cIAP2, which further induces the decrease of the ubiquitination of RIP1 to inhibit the activation of pro-survival signaling pathways and accelerate the necrosis of MDA-MB-231 cells. The disclosed mechanisms of SKO induced necrosis and apoptosis in our study is firstly reported, and it is believed that SKO could be considered as a potential candidate and further developed for the treatment of triple negative breast cancer.

Indexed as

ApoptosisBreast cancerNecrosisShikoninUbiquitination

Identifiers

PMID33526051
PMCPMC7851907
OpenAlexW3128831976

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 OpenQuestion graph.