Co-administration of apigenin with doxorubicin enhances anti-migration and antiproliferative effects via PI3K/PTEN/AKT pathway in prostate cancer cells
Küçük Resim Yok
Tarih
2021
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Morion LLC
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Prostate cancer is one of the leading cancers in men, and new approaches are needed for its treatment. The aim of this study was to investigate the effect of co-administration of naturally occurring flavone apigenin and doxorubicin to androgen-insensitive prostate cancer cells. Methods: The effect of the treatment on survival and migration of human PC3 cells was evaluated by MTT and scratch assay, respectively. Apoptosis and cell cycle distribution were detected by image-based cytometry. mRNA and protein expression were determined by real-time quantitative polymerase chain reaction and Western blot, respectively. Results: Apigenin and doxorubicin dose-dependently inhibited cell survival, and co-administration of both agents significantly induced cell death via upregulating the mRNA expression of caspases, Bax and cytochrome c, and downregulating Bcl-XL. Combination therapy caused cell cycle arrest by upregulating the expression of p21 and p27. The treatment modality inhibited cell migration via downregulating Snail, Twist and MMPs in which doxorubicin was ineffective. Apigenin dephosphorylated Akt strongly, significantly suppressed ERK phosphorylation, and increased PTEN expression 4.5-fold. The combination of apigenin and doxorubicin inhibited PI3K and AKT phosphorylation more strongly than a single administration. Conclusions: Our data indicate that a combination of the natural flavone apigenin with doxorubicin might have a potential in treatment of castration-resistant prostate cancer. Copyright © Experimental Oncology, 2021
Açıklama
Anahtar Kelimeler
Apigenin; Cell Migration; Doxorubicin; Pc3; Prostate Cancer, Apigenin; Caspase; Cytochrome C; Doxorubicin; Matrix Metalloproteinase; Messenger Rna; Phosphatidylinositol 3 Kinase; Phosphatidylinositol 3,4,5 Trisphosphate 3 Phosphatase; Protein Bax; Protein Bcl Xl; Protein Kinase B; Protein P21; Protein P27; Transcription Factor Snail; Transcription Factor Twist; Antineoplastic Agent; Apigenin; Doxorubicin; Phosphatidylinositol 3 Kinase; Phosphatidylinositol 3,4,5 Trisphosphate 3 Phosphatase; Protein Kinase B; Pten Protein, Human; Antiproliferative Activity; Apoptosis; Article; Cancer Cell; Cell Cycle Arrest; Cell Death; Cell Migration; Cell Survival; Controlled Study; Cytometry; Dose Response; Down Regulation; Drug Effect; Gene Expression; Human; Human Cell; Mtt Assay; Pc-3 [Human Prostate Carcinoma] Cell Line; Prostate Cancer; Protein Dephosphorylation; Protein Expression; Protein Phosphorylation; Real Time Polymerase Chain Reaction; Signal Transduction; Upregulation; Western Blotting; Wound Healing Assay; Castration Resistant Prostate Cancer; Cell Motion; Cell Proliferation; Drug Effect; Male; Pathology; Signal Transduction; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apigenin; Cell Movement; Cell Proliferation; Doxorubicin; Humans; Male; Pc-3 Cells; Phosphatidylinositol 3-Kinases; Prostatic Neoplasms, Castration-Resistant; Proto-Oncogene Proteins C-Akt; Pten Phosphohydrolase; Signal Transduction
Kaynak
Experimental Oncology
WoS Q Değeri
Scopus Q Değeri
Q4
Cilt
43
Sayı
2
