Gossypetin Is a Novel Modulator of Inflammatory Cytokine Production and a Suppressor of Osteosarcoma Cell Growth

• Published in: Antioxidants Vol. 12; no. 9; p. 1744
• Main Authors: Proença, Carina, Rufino, Ana Teresa, Santos, Isabela, Albuquerque, Hélio M. T, Silva, Artur M. S, Fernandes, Eduarda, Ferreira de Oliveira, José Miguel P
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01-09-2023; MDPI
• Subjects: 3,3′,4′,5,7,8-hexahydroxyflavone; Anti-inflammatory agents; Apoptosis; Autocrine signalling; B cells; Bone cancer; bone sarcoma; Cancer therapies; Carcinogenesis; Caspase-3; Cell culture; Cell growth; Cell viability; Chemoresistance; chemotherapeutic agents; Children; Cyclin-dependent kinases; Cytokines; Cytotoxicity; Ethylenediaminetetraacetic acid; flavonoid; Flavonoids; Growth factors; Inflammation; Interleukins; Kinases; Ligands; Metastases; Metastasis; Morphology; Osteosarcoma; Penicillin; proinflammatory cytokines; Radiation; St Louis Missouri; United States > US
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox12091744

Osteosarcoma (OS) is a common childhood sarcoma, and its treatment is hindered by adverse effects, chemoresistance, and recurrence. Interleukin (IL)-6 production by tumors plays a significant role in inflammation, carcinogenesis, and metastasis. This study aimed to investigate the antiproliferative potential of luteolin derivatives in OS and to evaluate interleukin production. MG-63, Saos-2, HOS, and 143B human OS cell lines were incubated with luteolin and eight derivatives containing hydroxy, chlorine, or alkyl substitutions. The cell viability and growth were evaluated in the presence of these compounds. Apoptosis was also examined through the analysis of the Bax expression and caspase-3 activity. Finally, the gossypetin effects were measured regarding the production of proinflammatory cytokines interleukin (IL)-6, IL-1β, and IL-12p70. Our findings show that gossypetin was the most potent compound, with proliferation-suppressing activities that induced a series of critical events, including the inhibition of the cell viability and growth. Apoptosis was associated with enhanced caspase-3 activity and increased Bax expression, indicating the involvement of the intrinsic pathway of apoptosis. Moreover, pre-/co-treatment with gossypetin significantly reduced the autocrine production of proinflammatory cytokines. Further investigation is required; nevertheless, considering the link between inflammation, carcinogenesis, and metastasis in OS, our findings suggest that gossypetin exhibits anti-proliferative and anti-inflammatory properties that are potentially relevant in the clinical context.