Details

Autor(en) / Beteiligte

• Debnath, Shibjyoti
• Sarkar, Abhisek
• Mukherjee, Dipanwita Das
• Ray, Subha
• Mahata, Barun
• Mahata, Tarun
• Parida, Pravat K.
• Das, Troyee
• Mukhopadhyay, Rupak
• Ghosh, Zhumur
• Biswas, Kaushik

Titel

Eriodictyol mediated selective targeting of the TNFR1/FADD/TRADD axis in cancer cells induce apoptosis and inhibit tumor progression and metastasis

Ist Teil von

• Translational oncology, 2022-07, Vol.21, p.101433-101433, Article 101433

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •Eriodictyol induces Selective Cytotoxicity to tumor cells.•Eriodictyol enhances TNFR1 expression in cancer cells.•Eriodictyol targets TNFR1 to selectively mediate apoptosis and cytotoxicity to cancer cells.•Eriodictyol reduces tumour burden in experimentally induced lung metastasis in vivo. While the anti-inflammatory activities of Eriodictyol, a plant-derived flavonoid is well-known, reports on its anti-cancer efficacy and selective cytotoxicity in cancer cells are still emerging. However, little is known regarding its mechanism of selective anti-cancer activities. Here, we show the mechanism of selective cytotoxicity of Eriodictyol towards cancer cells compared to normal cells. Investigation reveals that Eriodictyol significantly upregulates TNFR1 expression in tumor cells (HeLa and SK-RC-45) while sparing the normal cells (HEK, NKE and WI-38), which display negligible TNFR1 expression, irrespective of the absence or presence of Eriodictyol. Further investigation of the molecular events reveal that Eriodictyol induces apoptosis through expression of the pro-apoptotic DISC components leading to activation of the caspase cascade. In addition, CRISPR-Cas9 mediated knockout of TNFR1 completely blocks apoptosis in HeLa cells in response to Eriodictyol, confirming that Eriodictyol induced cancer cell apoptosis is indeed TNFR1-dependent. Finally, in vivo data demonstrates that Eriodictyol not only impedes tumor growth and progression, but also inhibits metastasis in mice implanted with 4T1 breast cancer cells. Thus, our study has identified Eriodictyol as a compound with high selectivity towards cancer cells through TNFR1 and suggests that it can be further explored for its prospect in cancer therapeutics.