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

Abstract

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.

Dataset of chicken-embryo blood cells exposed to quercetin, methyl methanesulfonate, or cadmium chloride

“…Cadmium chloride (CdCl 2, 133 µg/ml) and methyl methanesulfonate (MMS, 3.67 mg/ml) were dissolved directly in 1 % DMSO in PBS. The concentrations to use were based on previous experiments in vitro and in ovo [5] , [6] , [7] . All solutions were freshly prepared before inoculation.…”

The Potential Role of Gossypetin in the Treatment of Diabetes Mellitus and Its Associated Complications: A Review

“…It was also suggested that exposure to 50 mM gossypetin exhibits therapeutic effects against DNA damage at even a higher radiation dose exposure between 5 Gy and 20 Gy [55]. The aforementioned studies have demonstrated the anti-inflammatory and anti-oxidant properties of gossypetin in the management of radiation-induced oxidative stress (Figure 7) [55,70,72,73]. Taken together, gossypetin may alleviate oxidative-stress-induced diabetic complications due to its potent anti-oxidant and anti-inflammatory potential.…”

Role of bio‐flavonols and their derivatives in improving mitochondrial dysfunctions associated with pancreatic tumorigenesis

“…In esophageal cancer cells, gossypetin promotes cell cycle arrest and apoptosis by increasing the expression of apoptotic markers such as BAX, cytochrome c, and caspases 83 . Gossypetin suppresses inflammation and promotes apoptosis in osteosarcoma cell lines by reducing the levels of proinflammatory cytokines and increasing the expression of apoptotic proteins 205 …”