Anticancer Effect of Benzimidazole Derivatives, Especially Mebendazole, on Triple-Negative Breast Cancer (TNBC) and Radiotherapy-Resistant TNBC In Vivo and In Vitro.
Hoon Sik ChoiYoung Shin KoHana JinKi Mun KangIn Bong HaHojin JeongHaa-Na SongHye Jung KimBae Kwon JeongPublished in: Molecules (Basel, Switzerland) (2021)
In this study, we aimed to evaluate the anticancer effect of benzimidazole derivatives on triple-negative breast cancer (TNBC) and investigate its underlying mechanism of action. Several types of cancer and normal breast cells including MDA-MB-231, radiotherapy-resistant (RT-R) MDA-MB-231, and allograft mice were treated with six benzimidazole derivatives including mebendazole (MBZ). Cells were analyzed for viability, colony formation, scratch wound healing, Matrigel invasion, cell cycle, tubulin polymerization, and protein expression by using Western blotting. In mice, liver and kidney toxicity, changes in body weight and tumor volume, and incidence of lung metastasis were analyzed. Our study showed that MBZ significantly induced DNA damage, cell cycle arrest, and downregulation of cancer stem cell markers CD44 and OCT3/4, and cancer progression-related ESM-1 protein expression in TNBC and RT-R-TNBC cells. In conclusion, MBZ has the potential to be an effective anticancer agent that can overcome treatment resistance in TNBC.
Keyphrases
- cell cycle arrest
- cell death
- pi k akt
- induced apoptosis
- cell cycle
- dna damage
- cell proliferation
- oxidative stress
- signaling pathway
- molecular docking
- early stage
- papillary thyroid
- radiation therapy
- endoplasmic reticulum stress
- south africa
- type diabetes
- risk assessment
- squamous cell
- wound healing
- metabolic syndrome
- locally advanced
- young adults
- lymph node metastasis
- high glucose
- skeletal muscle
- drug induced
- cell migration
- human health