2-APB and CBD-Mediated Targeting of Charged Cytotoxic Compounds Into Tumor Cells Suggests the Involvement of TRPV2 Channels.
2-APB
BNL1 ME cells
TRPV2 channels
cannabidiol
doxorubicin
hepatocellular carcinoma
membrane permeation
targeted delivery
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2019
2019
Historique:
received:
26
07
2019
accepted:
17
09
2019
entrez:
5
11
2019
pubmed:
5
11
2019
medline:
5
11
2019
Statut:
epublish
Résumé
Targeted delivery of therapeutic compounds to particular cell types such that they only affect the target cells is of great clinical importance since it can minimize undesired side effects. For example, typical chemotherapeutic treatments used in the treatment of neoplastic disorders are cytotoxic not only to cancer cells but also to most normal cells when exposed to a critical concentration of the compound. As such, many chemotherapeutics exhibit severe side effects, often prohibiting their effective use in the treatment of cancer. Here, we describe a new means for facilitated delivery of a clinically used chemotherapy compound' doxorubicin, into hepatocellular carcinoma cell line (BNL1 ME). We demonstrate that these cells express a large pore, cation non-selective transient receptor potential (TRP) channel V2. We utilized this channel to shuttle doxorubicin into BNL1 ME cells. We show that co-application of either cannabidiol (CBD) or 2-APB, the activators of TRPV2 channels, together with doxorubicin leads to significantly higher accumulation of doxorubicin in BNL1 ME cells than in BNL1 ME cells that were exposed to doxorubicin alone. Moreover, we demonstrate that sub-effective doses of doxorubicin when co-applied with either 2-APB or CBD lead to a significant decrease in the number of living BNL1 ME cell and BNL1 ME cell colonies in comparison to application of doxorubicin alone. Finally, we demonstrate that the doxorubicin-mediated cell death is significantly more potent, requiring an order of magnitude lower dose, when co-applied with CBD than with 2-APB. We suggest that CBD may have a dual effect in promoting doxorubicin-mediated cell death by facilitating the entry of doxorubicin
Identifiants
pubmed: 31680972
doi: 10.3389/fphar.2019.01198
pmc: PMC6804401
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1198Informations de copyright
Copyright © 2019 Neumann-Raizel, Shilo, Lev, Mogilevsky, Katz, Shneor, Shaul, Leffler, Gabizon, Karni, Honigman and Binshtok.
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