Dibenzylideneacetone Induces Apoptosis in Cervical Cancer Cells through Ros-Mediated Mitochondrial Damage.
Aline Pinto ZaniCaroline Pinto ZaniZia Ud DinEdson Rodrigues-FilhoTânia Ueda-NakamuraFrancielle Pelegrin GarciaSueli de Oliveira Silva LautenschlagerCelso Vataru NakamuraPublished in: Antioxidants (Basel, Switzerland) (2023)
Cervical cancer is a health problem among women worldwide. Considering the limitations of prevention and antineoplastic chemotherapy against cervical cancer, research is needed to discover new, more effective, and safe antitumor agents. In the present study, we investigated the in vitro cytotoxicity of a new synthetic dibenzylideneacetone derived from 1,5-diaryl-3-oxo-1,4-pentadienyl ( A3K2A3 ) against cervical cancer cells immortalized by HPV 16 (SiHa), and 18 (HeLa) by MTT assay. Furthermore, we performed spectrofluorimetry, flow cytometry, and Western blot analyzes to explore the inhibitory mechanism of A3K2A3 in cervical cancer cells. A3K2A3 showed cytotoxic activity against both cell lines. Mitochondrial depolarization and reduction in intracellular ATP levels were observed, which may be dependent on the redox imbalance between increased ROS and reduced levels of the antioxidant defense. In addition, damage to the cell membrane and DNA, and effective blocking of cell division in the G2/M phase were detected, which possibly led to the induction of apoptosis. This result was further confirmed by the upregulation of apoptosis-related proteins Bax, cytochrome C, and caspases 9 and 3. Our results provided the first evidence that A3K2A3 contributes to the suppression of cervical cancer in vitro, showing promise as a possible alternative for the treatment of this cancer.
Keyphrases
- oxidative stress
- dna damage
- flow cytometry
- cell death
- cell cycle arrest
- induced apoptosis
- reactive oxygen species
- public health
- endoplasmic reticulum stress
- healthcare
- single cell
- polycystic ovary syndrome
- high throughput
- poor prognosis
- papillary thyroid
- south africa
- big data
- cell proliferation
- mental health
- high grade
- circulating tumor
- stem cells
- cell free
- squamous cell carcinoma
- locally advanced
- squamous cell
- metabolic syndrome
- pi k akt
- radiation therapy
- drug induced
- long non coding rna
- adipose tissue
- replacement therapy
- pregnancy outcomes
- circulating tumor cells