Enhancement of sorafenib-mediated death of Hepatocellular carcinoma cells by Carnosic acid and Vitamin D2 analog combination.
Abietanes
/ pharmacology
Antineoplastic Agents
/ pharmacology
Antioxidants
/ pharmacology
Apoptosis
/ drug effects
Autophagy
Bone Density Conservation Agents
/ pharmacology
Carcinoma, Hepatocellular
/ drug therapy
Cell Proliferation
Drug Synergism
Drug Therapy, Combination
Ergocalciferols
/ pharmacology
Humans
Liver Neoplasms
/ drug therapy
Signal Transduction
Sorafenib
/ pharmacology
Tumor Cells, Cultured
Carnosic acid
Caspase 3
Hepatoma
LC3-II
Sorafenib
Vitamin D
Journal
The Journal of steroid biochemistry and molecular biology
ISSN: 1879-1220
Titre abrégé: J Steroid Biochem Mol Biol
Pays: England
ID NLM: 9015483
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
24
07
2019
revised:
14
10
2019
accepted:
29
10
2019
pubmed:
11
11
2019
medline:
7
7
2020
entrez:
10
11
2019
Statut:
ppublish
Résumé
Hepatocellular carcinoma (HCC) is the most common form of liver cancer and it is the third leading cause of global cancer mortality. Sorafenib (Sf) is the first oral multi-kinase inhibitor approved for systemic treatment of advanced HCC, and can prolong survival, although only for three months longer than placebo treated patients. Preclinical studies showed that active forms of vitamin D can induce cell differentiation and regulate cell survival in several cell types, and epidemiological data link vitamin D insufficiency to an increased risk of neoplastic diseases, suggesting a potentially important role of vitamin D in cancer therapy. Other studies showed that the effect of vitamin D analogs on human neoplastic cells is potentiated by carnosic acid (CA), a plant polyphenol with anti-oxidant properties. Here we tested if the addition of the vitamin D2 analog Doxercalciferol (D2) together with CA can enhance the cytotoxic effect of Sf on HCC cell lines Huh7 (Sf-sensitive) and HCO2 (Sf-resistant). Indeed, this combination increased HCC cell death in cell lines, enhancing autophagy as well as apoptosis. Autophagy was confirmed by increased cytoplasmic vacuolation, perinuclear aggregation of LC3, and elevated protein levels of autophagy markers Beclin1, Atg3, and LC3. These results suggest that a regimen which combines a vitamin D2 analog/CA mixture with Sf can be a novel and promising therapeutic option for the treatment of HCC.
Identifiants
pubmed: 31704246
pii: S0960-0760(19)30437-6
doi: 10.1016/j.jsbmb.2019.105524
pmc: PMC7015782
mid: NIHMS1545338
pii:
doi:
Substances chimiques
Abietanes
0
Antineoplastic Agents
0
Antioxidants
0
Bone Density Conservation Agents
0
Ergocalciferols
0
1 alpha-hydroxyergocalciferol
3DIZ9LF5Y9
Sorafenib
9ZOQ3TZI87
salvin
LI791SXT24
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
105524Subventions
Organisme : NCI NIH HHS
ID : R01 CA044722
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK110024
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest All authors declare that they have no conflict of interest.
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