Apigenin induces apoptosis by regulating Akt and MAPK pathways in human melanoma cell A375SM.
Mol Med Rep
; 22(6): 4877-4889, 2020 Dec.
Article
en En
| MEDLINE
| ID: mdl-33174048
ABSTRACT
Apigenin, an aromatic compound, exhibits antioxidant, antiinflammatory and antiviral effects. The present study aimed to investigate the effects of apigenin on cell proliferation and apoptosis of human melanoma cells A375P and A375SM. Therefore, melanoma cells were treated with apigenin to determine its antiproliferative and survival effects, using wound healing and MTT assays. The results revealed that melanoma cell viability was decreased in a dosedependent manner. Furthermore, chromatin condensation, indicating apoptosis, was significantly increased in a dosedependent manner, as demonstrated by DAPI staining. In addition, increased apoptosis rate following treatment with apigenin was confirmed by Annexin Vpropidium iodide staining. The changes in the expression levels of apoptosisrelated proteins in A375P and A375SM melanoma cells were subsequently detected using western blot analysis. The results demonstrated that the protein expression levels of Bcl2 were decreased, whereas those of Bax, cleaved poly ADPribose polymerase, cleaved caspase9 and p53 were upregulated in a dosedependent manner in apigenintreated cells compared with those noted in untreated cells. In addition, in apigenintreated A375P cells, phosphorylated (p)p38 was upregulated and pextracellular signalregulated kinase (ERK), pcJun Nterminal kinase (JNK) and pprotein kinase B (Akt) were downregulated. However, in A375SM cells, apigenin treatment increased pERK and pJNK and decreased pp38 and pAkt protein expression levels. Subsequently, the inhibitory effect of apigenin on tumor growth was investigated in vivo. Tumor volume was significantly reduced in the 25 and 50 mg/kg apigenintreated groups compared with the control group. Additionally, a TUNEL assay was performed to detect apoptotic cells. Immunohistochemical staining also revealed elevated pERK expression in the apigenintreated group compared with the control group. Overall, the findings of the present study indicated that apigenin attenuated the growth of A375SM melanoma cells by inducing apoptosis via regulating the Akt and mitogenactivated protein kinase signaling pathways.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Apigenina
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Melanoma
Límite:
Animals
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Humans
/
Male
País como asunto:
Asia
Idioma:
En
Año:
2020
Tipo del documento:
Article