Lophira alata Suppresses Phorbol Ester-Mediated Increase in Cell Growth via Inhibition of Protein Kinase C-α/Akt in Glioblastoma Cells.
Antineoplastic Agents, Phytogenic
/ chemistry
Cell Proliferation
/ drug effects
Drug Screening Assays, Antitumor
Glioblastoma
/ drug therapy
Humans
Ochnaceae
/ chemistry
Phorbol Esters
/ pharmacology
Plant Extracts
/ chemistry
Protein Kinase C-alpha
/ antagonists & inhibitors
Protein Kinase Inhibitors
/ chemistry
Proto-Oncogene Proteins c-akt
/ antagonists & inhibitors
Tumor Cells, Cultured
Cancer
Lophira alata
apoptosis
cell proliferation
flavonoids
glioblastoma
natural products
protein kinase C.
Journal
Anti-cancer agents in medicinal chemistry
ISSN: 1875-5992
Titre abrégé: Anticancer Agents Med Chem
Pays: Netherlands
ID NLM: 101265649
Informations de publication
Date de publication:
2021
2021
Historique:
received:
15
09
2020
revised:
18
12
2020
accepted:
13
01
2021
pubmed:
25
2
2021
medline:
21
1
2022
entrez:
24
2
2021
Statut:
ppublish
Résumé
Medicinal plants serve as sources of compounds used to treat other types of cancers. The root of the plant Lophira alata (Ochnaceae) has been used as a component of traditional herbal decoctions administered to cancer patients in southwestern Nigeria. However, the mechanism of the cytotoxic effects of Lophira alata alone or in the presence of phorbol ester has not been investigated in brain tumor cells. This study aimed to examine the cytotoxic potential of the methanolic fraction of Lophira alata root on malignant glioma invasive cellular growth and survival. The methanolic fraction of Lophira alata (LAM) was subjected to high-performance liquid chromatography to determine the fingerprints of the active molecules. The antiproliferative effects of Lophira alata were assessed using the MTT and LDH assays. Protein immunoblots were carried out to test the effects of Lophira alata, alone or in the presence of phorbol ester, on survival signaling pathways, such as Akt, mTOR, and apoptotic markers such as PARP and caspases. The methanolic fraction of Lophira alata (LAM) induced a concentration-dependent and time-dependent decrease in glioma cell proliferation. In addition, LAM attenuated phorbol ester-mediated signaling of downstream targets such as Akt/mTOR. Gene silencing using siRNA targeting PKC-alpha attenuated LAM-mediated downregulation of Akt. In addition, LAM induced both PARP and caspase cleavages. The HPLC fingerprint of the fraction indicates the presence of flavonoids. LAM decreases cell proliferation and induces apoptosis in glioma cell lines and thus could serve as a therapeutic molecule in the management of gliomas.
Sections du résumé
BACKGROUND
Medicinal plants serve as sources of compounds used to treat other types of cancers. The root of the plant Lophira alata (Ochnaceae) has been used as a component of traditional herbal decoctions administered to cancer patients in southwestern Nigeria. However, the mechanism of the cytotoxic effects of Lophira alata alone or in the presence of phorbol ester has not been investigated in brain tumor cells.
OBJECTIVE
This study aimed to examine the cytotoxic potential of the methanolic fraction of Lophira alata root on malignant glioma invasive cellular growth and survival.
METHODS
The methanolic fraction of Lophira alata (LAM) was subjected to high-performance liquid chromatography to determine the fingerprints of the active molecules. The antiproliferative effects of Lophira alata were assessed using the MTT and LDH assays. Protein immunoblots were carried out to test the effects of Lophira alata, alone or in the presence of phorbol ester, on survival signaling pathways, such as Akt, mTOR, and apoptotic markers such as PARP and caspases.
RESULTS
The methanolic fraction of Lophira alata (LAM) induced a concentration-dependent and time-dependent decrease in glioma cell proliferation. In addition, LAM attenuated phorbol ester-mediated signaling of downstream targets such as Akt/mTOR. Gene silencing using siRNA targeting PKC-alpha attenuated LAM-mediated downregulation of Akt. In addition, LAM induced both PARP and caspase cleavages. The HPLC fingerprint of the fraction indicates the presence of flavonoids.
CONCLUSION
LAM decreases cell proliferation and induces apoptosis in glioma cell lines and thus could serve as a therapeutic molecule in the management of gliomas.
Identifiants
pubmed: 33622229
pii: ACAMC-EPUB-114455
doi: 10.2174/1871520621666210223094235
doi:
Substances chimiques
Antineoplastic Agents, Phytogenic
0
Phorbol Esters
0
Plant Extracts
0
Protein Kinase Inhibitors
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Protein Kinase C-alpha
EC 2.7.11.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2512-2519Subventions
Organisme : Cedarville University School of Pharmacy Ohio
ID : CUSOP/2019-20/04
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.