The effects of the Wnt/β‑catenin signaling pathway on apoptosis in HeLa cells induced by carbon ion irradiation

Abstract

The molecular mechanisms underlying the biological effects of carbon ions are unclear. The aim of this study was to explore the Wnt/β-catenin pathway in regulating carbon ion ( 12 C 6+ ) radiation-induced cellular toxicity. HLY78 is a Wnt-specific small molecular modulator, whose effects on 12 C 6+ radiation-induced damage are mostly unknown. HLY78, in combination with 12 C 6+ radiation was investigated on HeLa cell viability, cell cycle progression, DNA damage, and the expression of apoptotic and Wnt-related proteins. 12 C 6+ radiation suppressed cell viability in a time-dependent manner, whereas the addition of HLY78 to cells significantly reduced this stress. Moreover, after irradiation with 12 C 6+ , HeLa cells exhibited increased cell apoptosis, G2/M phase arrest, and a number of γ-H2AX foci. However, Wnt signaling activation alleviated these effects. Furthermore, when compared with the radiation alone group, supplementation with HLY78 markedly increased the expression of anti-apoptotic and Wnt-related proteins, and significantly decreased the expression of apoptotic proteins. The present results indicated that activation of the Wnt/β-catenin signaling pathway by HLY78 reduced 12 C 6+ radiation-induced HeLa cell dysfunction, suggesting that the Wnt/β-catenin signaling pathway plays an important role in regulating 12 C 6+ radiation-induced cellular toxicity in HeLa cells.

Carbon ions trigger DNA damage response to overcome radioresistance by regulating β‐catenin signaling in quiescent HeLa cells

“…Carbon ions were found to downregulate the expression of Wnt3a and β‐catenin in proliferating HeLa cells, consistent with our previous findings (Si et al, 2020; Zhang et al, 2020). In contrast, carbon ions upregulated Wnt3a and β‐catenin levels in quiescent cells, thereby activating the β‐catenin signaling pathway.…”

“…The β‐catenin signaling pathway plays a substantial role in tumorigenesis and tumor propagation. Our previous studies revealed that inhibition of Wnt/β‐catenin signaling effectively sensitizes HeLa cells to carbon ion radiation, whereas activation of Wnt/β‐catenin signaling reduces carbon ion radiation‐induced dysfunction in human cervical cancer HeLa cells (Si et al, 2020; Zhang et al, 2020). These results verified that β‐catenin signaling is involved in the regulation of the radiosensitivity of HeLa cells.…”

“…The experimental protocols were performed as described previously (Si et al, 2020; Zhang et al, 2020).…”

“…There is growing evidence that deregulation of β‐catenin signaling is associated with tumor radioresistance in several types of human cancers, including breast cancer, head and neck cancer, prostate cancer, glioblastoma, and colorectal cancer (Yao et al, 2020). In addition, our previous studies revealed that the β‐catenin signaling pathway plays an important role in the regulation of radiosensitivity in HeLa cells and may be a promising therapeutic target for cervical cancer (Si et al, 2020; Zhang et al, 2020). However, whether this pathway is involved in overcoming radioresistance in quiescent cancer cells remains unclear.…”

Ginsenoside Rh4 Suppresses Metastasis of Esophageal Cancer and Expression of c-Myc via Targeting the Wnt/β-Catenin Signaling Pathway

“…HLY78 is an agonist of the Wnt/β-catenin signaling pathway. HLY78 can enhance Wnt signaling by targeting the DIX domain of Axin in the channel and enhancing Axin-LRP6 cross-linking [ 48 , 49 , 50 ]. We pretreated with the Wnt agonist HLY78 to investigate the crucial utility of ginsenoside Rh4.…”