Evidence map›Paper›PMID 30111296›Full record

ArticleBMC cancer2018

Targeting colorectal cancer cell metabolism through development of cisplatin and metformin nano-cubosomes.

Mona M Saber, Abdulaziz M Al-Mahallawi, Noha N Nassar, Björn Stork, Samia A Shouman

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 8% 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

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.

  1. Changes in fatigue in rectal cancer patients before and after therapy: a systematic review and meta-analysis.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2020
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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

5 authors at 2 institutions in 2 countries.

Mona M SaberDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St, Cairo, 11562, Egypt. mona.magdy@pharma.cu.edu.eg.
Abdulaziz M Al-MahallawiDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini St, Cairo, 11562, Egypt.
Noha N NassarDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St, Cairo, 11562, Egypt.
Björn StorkInstitute of Molecular Medicine I, Medical Faculty, Heinrich-Heine-University, Universitätsstr. 1, Building 23.12, 40225, Düsseldorf, Germany. bjoern.stork@uni-duesseldorf.de.ORCID http://orcid.org/0000-0002-4167-7806
Samia A ShoumanPharmacology Unit, Department of Cancer Biology, National Cancer Institute, Cairo University, Kasr El-Aini St., Fom El Khalig, Cairo, 11796, Egypt.
Cairo University · EGHeinrich Heine University Düsseldorf · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundColorectal cancer (CRC) remains a leading cause of death worldwide. Utilizing cisplatin in CRC is correlated with severe adverse effects and drug-resistance. Combined anticancer drug-treatment, along with, their enhanced delivery, can effectively kill cancer through multiple pathways. Nano-cubosomes are emerging as nanocarriers for anticancer therapies, hence, we constructed nano-cubosomes bearing cisplatin and cisplatin-metformin combination for investigation on HCT-116 cells.

methodsNano-cubosomes bearing either cisplatin alone or cisplatin-metformin combination were formulated using emulsification technique. The loaded nano-cubosomes were characterized in vitro and the optimized formulation was selected. Their cytotoxic effects were investigated by Sulphorhodamine-B (SRB) assay. The AMPK/mTOR metabolic pathway as well as the Akt/mTOR pathway were analyzed using ELISA technique. Colorimetry was used in NADPH oxidase, LDH and caspase-3 activity determination.

resultsnano-cubosomal formulations exhibited superior cytotoxic effect compared to unformulated cisplatin. This cytotoxic effect was profound upon incorporation of metformin, an indirect mTOR inhibitor, in cisplatin nano-cubosomes. The induced CRC cell apoptosis was through inhibition of several metabolic pathways, namely, AMPK/mTOR and Akt/mTOR. Drug-loaded nano-cubosomes ensued depletion in glucose and energy levels that led to AMPK activation and thus mTOR inhibition. mTOR was additionally inhibited via suppression of p-Akt (Ser473) levels after nano-cubosomal treatment. Moreover, drug-loaded nano-cubosomes produced a notable escalation in ROS levels, evident as an increase in NADPH oxidase, inhibition of LDH and a consequential upsurge in caspase-3.

conclusionThese results demonstrated the influence exerted by cisplatin-loaded nano-cubosomes on CRC cell survival and enhancement of their cytotoxicity upon metformin addition.

Indexed as

AMP-Activated Protein Kinase KinasesAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisAutophagyCaspase 3Cell SurvivalCisplatinColorectal NeoplasmsDrug SynergismGene Expression Regulation, NeoplasticHCT116 CellsHumansMetforminMiceNanostructuresAMP-Activated Protein Kinase KinasesCaspase 3CisplatinMetforminMTOR protein, humanProtein KinasesTOR Serine-Threonine KinasesAMPKCisplatinMetforminmTORNano-cubosomes

Identifiers

PMID30111296
PMCPMC6094476
OpenAlexW2885478276

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.