Piperlongumine, a piper alkaloid, enhances the efficacy of doxorubicin in breast cancer: involvement of glucose import, ROS, NF-κB and lncRNAs.
Alkaloids
/ pharmacology
Animals
Antineoplastic Agents
/ pharmacology
Apoptosis
Breast Neoplasms
/ drug therapy
Cell Line, Tumor
Dioxolanes
/ pharmacology
Doxorubicin
/ pharmacology
Female
Glucose
/ pharmacology
Humans
Mice
Molecular Docking Simulation
NF-kappa B
/ genetics
Piper
/ chemistry
RNA, Long Noncoding
/ genetics
Reactive Oxygen Species
/ metabolism
Alkaloid
Chemoresistance
LncRNA
NF-κB
Piperlongumine
Warburg effect
Journal
Apoptosis : an international journal on programmed cell death
ISSN: 1573-675X
Titre abrégé: Apoptosis
Pays: Netherlands
ID NLM: 9712129
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
accepted:
08
01
2022
pubmed:
6
2
2022
medline:
7
5
2022
entrez:
5
2
2022
Statut:
ppublish
Résumé
Piperlongumine (PL, piplartine) is an alkaloid derived from the Piper longum L. (long pepper) roots. Originally discovered in 1961, the biological activities of this molecule against some cancer types was reported during the last decade. Whether PL can synergize with doxorubicin and the underlying mechanism in breast cancer remains elusive. Herein, we report the activities of PL in numerous breast cancer cell lines. PL reduced the migration and colony formation by cancer cells. An enhancement in the sub-G1 population, reduction in the mitochondrial membrane potential, chromatin condensation, DNA laddering and suppression in the cell survival proteins was observed by the alkaloid. Further, PL induced ROS generation in breast cancer cells. While TNF-α induced p65 nuclear translocation, PL suppressed the translocation in cancer cells. The expression of lncRNAs such as MEG3, GAS5 and H19 were also modulated by the alkaloid. The molecular docking studies revealed that PL can interact with both p65 and p50 subunits. PL reduced the glucose import and altered the pH of the medium towards the alkaline side. PL also suppressed the expression of glucose and lactate transporter in breast cancer cells. In tumor bearing mouse model, PL was found to synergize with doxorubicin and reduced the size, volume and weight of the tumor. Overall, the effects of doxorubicin in cancer cells are enhanced by PL. The modulation of glucose import, NF-κB activation and lncRNAs expression may have contributory role for the activities of PL in breast cancer.
Identifiants
pubmed: 35122181
doi: 10.1007/s10495-022-01711-6
pii: 10.1007/s10495-022-01711-6
doi:
Substances chimiques
Alkaloids
0
Antineoplastic Agents
0
Dioxolanes
0
NF-kappa B
0
RNA, Long Noncoding
0
Reactive Oxygen Species
0
Doxorubicin
80168379AG
piperlongumine
SGD66V4SVJ
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
261-282Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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