Transformation of nomifensine using ionizing radiation and exploration of its anticancer effects in MCF‑7 cells

Abstract

Breast cancer is one of the most challenging diseases to treat in humans worldwide. There are several alternatives in treating this life-threatening disease; however, chemoresistance is probably the biggest obstacle to the treatment of breast cancer. It may be essential to develop a therapeutic candidate material with less reversible effects and high treatment efficiency to solve this problem. The present study applied an ionizing radiation approach employing nomifensine (NF) to transform its chemical characteristics and investigated its potential to kill human breast cancer cells (MCF-7). Irradiated (IR-) NF was analyzed using high-performance liquid chromatography. The findings showed that NF inhibited the proliferation of breast cancer cells and increased the rate of apoptosis. In addition, IR-NF induced the accumulation of cytosolic reactive oxygen species and enhanced mitochondrial aggregation. Additionally, mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2, p38 and c-Jun NH 2-terminal kinase) were involved in damage signaling induced by IR-NF and IR-NF suppressed β-catenin nuclear translocation. It is suggested that irradiation can be an effective method to maximize the efficacy of existing drugs and that IR-NF has the potential to be a drug candidate for treating patients with breast cancer.

Ionizing radiation‑induced modification of nialamide as an anti‑inflammatory agent against lipopolysaccharide‑induced RAW 264.7 and DH82 cells

“…Among these derivatives, it was found that hydroxylation at the C-11 position of HBPA conferred the most potent inhibitory activity against the activation of pro-inflammatory mediators ( Table I ). Comparatively, the simple pyridine amide isonicotinamide ( 7 ) was characterized by relatively lower inhibitory activity against the production of both NO and PGE 2 in RAW 264.7 macrophages ( Table I ). Consistently, in canine DH82 macrophages, the hydroxyl-substituted benzylpropanamide derivative was established have the most potent inhibitory activity against the production of NO and PGE 2 , with IC 50 values of 57.5±0.6 and 49.4±0.4 µM, respectively ( Table I ).…”

“…of hydrazine-based nomifensine has been demonstrated to enhance the anticancer effects of this drug in treated breast cancer cells (7). Radiolytic radicals are powerful modifying agents that can initiate a range of modification reactions in lead compounds during irradiation (47).…”

“…It has been widely suggested that γ irradiation can enhance the anti-inflammatory effect of natural products ( 5 , 6 ). Furthermore, we have previously demonstrated that γ irradiation combined with the anti-depressant nomifensine (Merital) can contribute to the suppression of the proliferation of breast cancer cells ( 7 ). Given its diverse properties, ionizing radiation may thus represent an innovative technique for the development of incrementally modified drugs.…”

Novel aminopyridazine derivative of minaprine modified by radiolysis presents potent anti-inflammatory effects in LPS-stimulated RAW 264.7 and DH82 macrophage cells

“…In a recent study, chrysin and luteolin showed improved anti-in ammatory activities in vitro and in vivo induced by γ-irradiation, and the chemical structure of hydroxyalkyl-substituted compounds was identi ed 12,21 . In addition, radiolytic transformation of alkaloids and steroids showed potent enhanced anti-cancer effects in melanoma, breast, liver, and lung cancer 11,[22][23][24][25] .…”

“…Gamma irradiation has received wide attention owing to its potential to decrease the toxicity of alkaloids, steroids, and avonoids and increase the biological capacities of these compounds 10,11 . Recently, the anti-depressant drug nomifensine (Merital®) was reported to effectively improve the anti-cancer properties in breast cancer cells after exposed to ionizing radiation 12 .…”