Dibenzylideneacetone Induces Apoptosis in Cervical Cancer Cells through Ros-Mediated Mitochondrial Damage

• Main Authors: Aline Pinto Zani (Author), Caroline Pinto Zani (Author), Zia Ud Din (Author), Edson Rodrigues-Filho (Author), Tânia Ueda-Nakamura (Author), Francielle Pelegrin Garcia (Author), Sueli de Oliveira Silva (Author), Celso Vataru Nakamura (Author)
• Format: Book
• Published: MDPI AG, 2023-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antiox12020317; 2076-3921
• Keywords: dibenzylideneacetone; apoptosis; oxidative stress; HeLa cell; SiHa cell; Therapeutics. Pharmacology; RM1-950
• Source: Antioxidants, Vol 12, Iss 2, p 317 (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 (<b>A3K2A3</b>) 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 <b>A3K2A3</b> in cervical cancer cells. <b>A3K2A3</b> 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 <b>A3K2A3</b> contributes to the suppression of cervical cancer in vitro, showing promise as a possible alternative for the treatment of this cancer.