Impact of Curcumin, Raspberry Extract, and Neem Leaf Extract on Rel Protein-regulated Cell Death/radiosensitization in Pancreatic Cancer Cells
Overview
Authors
Affiliations
Objectives: Nuclear factor κB (NF-κB) plays an intrinsic role in promoting growth, angiogenesis, and metastasis in pancreatic cancer (PC) and serves as a mechanism underlying therapeutic resistance. Accordingly, we investigated the efficacy of bioactive phytochemicals in inhibiting radiotherapy (RT)-induced NF-κB activity, signaling, and NF-κB-dependent regulation of cell death.
Methods: Panc-1, BxPC-3, and MIA PaCa-2 cells exposed to 10 Gy (single high dose [SDR]) or 2 Gy/d for 5 days (fractionated radiation [FIR]) with or without curcumin (CUR), neem leaf extract (NLE), or black raspberry extract (RSE) were analyzed.
Results: Radiotherapy profoundly induced NF-κB-DNA-binding activity with relatively robust activation after FIR. Curcumin, NLE, and RSE significantly inhibited both constitutive and RT-induced NF-κB. Furthermore, quantitative polymerase chain reaction profiling of 88 NF-κB pathway molecules demonstrated that CUR, NLE, and RSE comprehensively, yet differentially inhibited FIR/SDR-induced genes. Functionally, CUR, NLE, and RSE markedly conferred RT-inhibited cell viability/survival, robustly activated caspase-3/7 activity, and subsequent cell death. More importantly, NF-κB overexpression and silencing studies demonstrate that these compounds potentiate RT-induced cell death by targeting RT-induced NF-κB.
Conclusions: These data strongly imply that CUR, NLE, and RSE may serve as effective "deliverables" to potentiate RT in PC cure and further throw light that these phytochemicals-induced cell killing may involve selective regulation of RT-induced NF-κB.
Impact of dietary ingredients on radioprotection and radiosensitization: a comprehensive review.
Islam M, Sultana N, Liu C, Mao A, Katsube T, Wang B Ann Med. 2024; 56(1):2396558.
PMID: 39320122 PMC: 11425709. DOI: 10.1080/07853890.2024.2396558.
Nimbolide Inhibits SOD2 to Control Pancreatic Ductal Adenocarcinoma Growth and Metastasis.
Mehmetoglu-Gurbuz T, Lakshmanaswamy R, Perez K, Sandoval M, Jimenez C, Rocha J Antioxidants (Basel). 2023; 12(10).
PMID: 37891871 PMC: 10604165. DOI: 10.3390/antiox12101791.
Raissa R, Riawan W, Safitri A, Masruri M, Beltran M, Aulanniam A F1000Res. 2023; 11:477.
PMID: 37829248 PMC: 10565427. DOI: 10.12688/f1000research.109557.1.
Arif M, Nawaz A, Khan S, Mueen H, Rashid F, Hemeg H Heliyon. 2023; 9(6):e17252.
PMID: 37389057 PMC: 10300336. DOI: 10.1016/j.heliyon.2023.e17252.
Zargan S, Barough M, Zargan J, Shayesteh M, Haji Noor Mohammadi A, Mousavi M Iran Biomed J. 2022; 26(6):475-84.
PMID: 36380684 PMC: 9841218. DOI: 10.52547/ibj.3756.