Effect and mechanisms of celastrol on the apoptosis of HOS osteosarcoma cells

Abstract

Osteosarcoma is the most common primary malignant tumor of the bone found predominantly in children and teenagers and results in early metastasis and poor prognosis. The present study primarily focused on the impact of celastrol on apoptosis and autophagy of osteosarcoma HOS cells, as well as the related mechanisms. Following the appropriate treatment, the human osteosarcoma cell line HOS was assessed for viability, Ca2+ in cells, apoptosis and changes in cell morphology using Cell Counting Kit-8, flow cytometry, inverted phase contrast microscope, Hoechst staining and transmission electron microscopy. The expression levels of various proteins, including endoplasmic reticulum stress (ERS)-related proteins (Bip, PERK, p-PERK, IRE1α, calnexin, PDI and Erol‑Lα), apoptosis-related proteins (CHOP, cleaved caspase‑12), mitochondrial apoptosis-related proteins (Bax, Bcl-2 and cytochrome c), cleaved caspase-3, and autophagy-related proteins (LC3-Ⅰ, LC3-Ⅱ and P62) and β-actin, were assessed with western blotting. Celastrol significantly inhibited the viability of HOS cells in a dose-dependent manner and promoted the expression of ERS-related, apoptosis-related and mitochondrial apoptosis-related proteins. The ERS inhibitor tauroursodeoxycholate promoted celastrol-induced autophagy and apoptosis of HOS cells. Pretreatment with the PERK inhibitor GSK2656157 significantly promoted celastrol-induced death and attenuated HOS cell autophagy. Our results indicated that the ERS pathway and the mitochondrial pathway were involved in celastrol-induced apoptosis of HOS cells. The ERS/PERK pathway may protect HOS cells from apoptosis by celastrol and may play a complicated role in the process of autophagy.

<p>The Toxicity Of Metallic Nanoparticles On Liver: The Subcellular Damages, Mechanisms, And Outcomes</p>

“…Hepatocyte apoptosis is characterized by nuclear chromatin condensation, nuclear rupture, cell contraction, plasma membrane vacuolation, DNA damage, lack of nutrition and cytokine release, which reflect the activation of cell surface death receptors and apoptotic factors. 87–90…”

Stressed: The Unfolded Protein Response in T Cell Development, Activation, and Function

“…While Zheng et al did not explore whether IL-17 was elevated in their obese mice experiencing airway allergic responses, they do find neutrophil infiltration increased in the lung, and Th17 cells play an important role in recruiting neutrophils [75,186]. Treating obese mice with celastrol, a drug known to promote apoptosis in cancer cells via activation of IRE1, ATF4, and CHOP, reduces airway hyperresponsiveness and IL-17 production [185,187,188,189]. These studies indicate that targeting UPR in obesity mediated asthma may prove beneficial for treatment.…”

Autophagy in the pharmacological activities of celastrol (Review)

“…Extensive experimentation has indicated that autophagy modulation may be an important mechanism underlying the anti-tumor therapeutic effect of celastrol (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Celastrol also alleviates inflammatory reactions and restrains the immune response through autophagic pathways (31)(32)(33)(34)(35)(36)(37)(38)(39)(40).…”