Parthenolide ameliorates tweak-induced podocytes injury

Yu, Lichun; Zhang, Caihui; Chen, Yuan; Li, Qian; Wang, Jing; Sun, Song

doi:10.1007/s11033-020-05591-4

Cited by 1 publication

(1 citation statement)

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“…This could reflect the cisplatin dosing scheme and sample collection time but may also suggest that DMAPT recruits additional nephroprotective mechanisms. In fact, recent data show that parthenolide has anti‐apoptotic effects over podocytes from renal glomeruli [39], potentially explaining the reduced glomerular damage we observed. These promising results warrant a more detailed study of the mechanisms underlying DMAPT's protective activity.…”

Section: Discussionmentioning

confidence: 69%

Pharmacological NF‐κB inhibition decreases cisplatin chemoresistance in muscle‐invasive bladder cancer and reduces cisplatin‐induced toxicities.

et al. 2023

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Most patients with muscle‐invasive bladder cancer (MIBC) are not cured with platinum chemotherapy. Up‐regulation of nuclear factor kappa light chain enhancer of activated B cells (NF‐κB) is a major mechanism underlying chemoresistance, suggesting that its pharmacological inhibition may increase platinum efficacy. NF‐κB signaling was investigated in two patient cohorts. The Cancer Genome Atlas (TCGA) was used to correlate NF‐κB signaling and patient survival. The efficacy of cisplatin plus the NF‐κB inhibitor dimethylaminoparthenolide (DMAPT) versus cisplatin or DMAPT alone was tested in vitro. Xenografted and immunocompetent MIBC mouse models were studied in vivo. Platinum‐naive claudin‐low MIBC showed constitutive NF‐κB signaling and this was associated with reduced disease‐specific survival in TCGA patients. Chemotherapy up‐regulated NF‐κB signaling and chemoresistance‐associated genes, including SPHK1, PLAUR and SERPINE1. In mice, DMAPT significantly improved the efficacy of cisplatin in both models. The combination preserved body weight, renal function and morphology, reduced muscle fatigue and IL‐6 serum levels, and did not aggravate immuno‐hematological toxicity compared with cisplatin alone. These data provide a rationale for combining NF‐κB inhibition with platinum‐based chemotherapy and conducting a clinical trial in MIBC patients.

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Section: Discussionmentioning

confidence: 69%