αPhellandrene enhances the apoptosis of HT29 cells induced by 5fluorouracil by modulating the mitochondriadependent pathway.
Oncol Rep
; 51(4)2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38456489
ABSTRACT
αPhellandrene (αPA), a natural constituent of herbs, inhibits cancer cell viability and proliferation. 5Fluorouracil (5FU) is a frequently utilized chemotherapeutic medicine for the treatment of colon cancer, which works by triggering cancer cell apoptosis. The present study examined how the combination of αPA and 5FU affects the suppression of human colon cancer cells by promoting apoptosis. The impact of this treatment on cell viability, apoptosis, and the expression levels of Bcl2 family members, caspase family members and mitochondriarelated molecules in HT29 cells was assessed by the MTT assay, immunocytochemistry, western blotting and quantitative PCR. The combination of 5FU and αPA had a synergistic inhibitory effect on cell viability, as determined by assessing the combination index value. Bax protein expression levels were higher in the 50, 100 or 250 µM αPA combined with 5FU groups compared with those in the 5FU alone group (P<0.05). By contrast, Bcl2 protein expression levels and mitochondrial membrane potential (MMP, ΔΨm) were lower in the 100 or 250 µM αPA combined with 5FU groups than those in the 5FU alone group (P<0.05). In addition, hexokinase2 (HK2) protein expression levels were lower in the 50, 100 or 250 µM αPA combined with 5FU groups than those in the 5FU alone group (P<0.05). Compared with 5FU alone, after HT29 cells were treated with 50, 100 or 250 µM αPA combined with 5FU, the mRNA expression levels of extrinsicinduced apoptotic molecules, including caspase8 and Bid, were higher (P<0.05). Treatment with 50, 100 or 250 µM αPA combined with 5FU also increased the mRNA expression levels of cytochrome c, caspase9 and caspase3, regulating intrinsic apoptosis (P<0.05). These results showed that αPA and 5FU had a synergistic effect on reducing the viability of human colon cancer HT29 cells by inducing extrinsic and intrinsic apoptosis pathways. The mechanism by which apoptosis is induced may involve the intrinsic apoptosis pathway that activates the mitochondriadependent pathway, including regulating the expression levels of Bcl2 family members, including Bax, Bcl2 and Bid, regulating MMP and HK2 expression levels, and increasing the expression of caspase cascade molecules, including caspase9 and caspase3. In addition, it may involve the extrinsic apoptosis pathway that activates caspase8 and caspase3 leading to apoptosis.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Colo
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Fluoruracila
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Monoterpenos Cicloexânicos
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article