Ferulic Acid Induces Apoptosis of HeLa and Caski Cervical Carcinoma Cells by Down-Regulating the Phosphatidylinositol 3-Kinase (PI3K)/Akt Signaling Pathway
Authors: Shiwei Peng
Sihong Zhu
Yan Tong
Liping Luo
Journal: Medical Science Monitor (2020)
Discipline: CLINICAL MEDICINE
Keywords: Ferulic acid; cancer cells; cervical carcinoma; apoptosis; Mcl-1
Affiliations: Department of Obstetrics, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China (mainland)., Department of Obstetrics and Gynecology, Jiangxi Health Vocational College, Nanchang, Jiangxi, China (mainland)., Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China (mainland)., Department of Obstetrics and Gynecology, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, China (mainland).

Abstract:  BACKGROUND Ferulic acid is an antioxidant phenolic compound derived from plants, which has effects on cancer cells. This study aimed to investigate the effects of ferulic acid on HeLa and Caski human cervical carcinoma cells and the molecular mechanisms involved. MATERIAL AND METHODS HeLa and Caski human cervical carcinoma cells were grown in culture and treated with increasing doses of ferulic acid. The MTT assay was used to evaluate cell viability. Flow cytometry was performed with 4',6-diamidino-2-phenylindole (DAPI) and Annexin V staining for cell apoptosis. The expression of myeloid leukemia cell differentiation-1 (Mcl-1) protein and MCL-1 mRNA were determined by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS Ferulic acid significantly reduced HeLa and Caski cell viability in the concentration range of 4-20 ¬µM (P&lt;0.05). Ferulic acid treatment promoted DNA condensation and significantly increased apoptosis in Caski cells (P&lt;0.05). Ferulic acid treatment resulted in the activation of pro-caspase-3, pro-caspase-8, pro-caspase-9, and PARP. The MTT assay showed that ferulic acid did not reduce the viability of Caski cells treated with the caspase inhibitor, z-VAD-fmk. Ferulic acid reduced the levels of Bcl-2 and Mcl-1, and increased the levels of Bax and reactive oxygen species (ROS). In Caski cells, Akt and PI3K phosphorylation were reduced by ferulic acid in a concentration-dependent manner. CONCLUSIONS The effects of ferulic acid were dose-dependent and resulted in cell cytotoxicity and apoptosis of HeLa and Caski cells, and the PI3K/Akt signaling pathway was down-regulated in Caski cells. 

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 Figure 5.  The effect of ferulic acid on the production of reactive oxygen species (ROS) in Caski human cervical carcinoma cells. Caski human cervical carcinoma cells following treatment with ferulic acid for 48 h were stained with 2,7-dichloro-dihydro-fluorescein diacetate (DCFH-DA) and observed by flow cytometry.  The Control panel is calling out for an explanation. , 
 Figure 2.  Induction of apoptosis by ferulic acid in Caski human cervical carcinoma cells. Ferulic acid was added to cultures of HeLa and Caski human cervical carcinoma cells at concentrations of 4, 8, 16, and 20 u00b5M. (A) Staining with 4u2019,6-diamidino-2- phenylindole (DAPI) of nuclear DNA condensation of the cells is shown by flow cytometry .  This is not flow cytometry, and these are not realistic configurations of cell cultures. Are the purported results for HeLa cells, Caski cells, or a mixture? ,