Conjugation of the Fn14 Ligand to a SMAC Mimetic Selectively Suppresses Experimental Squamous Cell Carcinoma in Mice

Wang, Xiaoyu; Lu, Mengji; Gu, Hanjiang; Xiao, Tong; Hu, Guanglei; Luo, Mai; Xia, Yumin

doi:10.1016/j.jid.2022.08.039

Cited by 1 publication

(1 citation statement)

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“…Various small molecules or compounds mimicking SMAC proteins activity (Smac mimetics) demonstrated a promising role in sensitizing cancer cells to cytotoxic drugs and are under clinical trial [ 10 , 11 , 12 ]. In a recent study, a Smac mimetic compound MV1 was conjugated to a ligand of Fn14, and TWEAK suppressed squamous cell carcinoma (SCC) both in vitro and in vivo [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

SMAC Mimetic BV6 Co-Treatment Downregulates the Factors Involved in Resistance and Relapse of Cancer: IAPs and Autophagy

Rafat

Singh

Pandey

et al. 2022

Biology

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Cancer is the utmost common disease-causing death worldwide, characterized by uncontrollable cell division with the potential of metastasis. Overexpression of the Inhibitors of Apoptosis proteins (IAPs) and autophagy correlates with tumorigenesis, therapeutic resistance, and reoccurrence after anticancer therapies. This study illuminates the role and efficacy of smac mimetic compound BV6 alone and in co-treatment with death ligands such as TRAIL and TNFα in the regulation of cell death mechanisms, i.e., apoptosis and autophagy. In this study, MTT assays, wound healing assays, and cellular and nuclear morphological studies were done. DAPI staining, AO/EtBr staining and AnnexinV/PI FACS was done to study the apoptosis. The expression of IAPs and autophagy biomarkers was analyzed using Real time-PCR and western blotting. Meanwhile, TEM demonstrated autophagy and cellular autophagic vacuoles in response to the BV6. The result shows a promising anti-cancer effect of BV6 alone as well as in combinational treatment with TRAIL and TNFα, compared to the lone treatment of TRAIL and TNFα in both breast cancer cell lines. The smac mimetic compound might provide an alternative combinational therapy with conventional anticancer therapies to tackle their inefficiency at the advanced stage of cancer, cancer resistance, and reoccurrence. Also, IAPs and autophagic proteins could act as potent target molecules for the development of novel anti-cancer drugs in pathogenesis and the betterment of regimens for cancer.

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Section: Introductionmentioning

confidence: 99%