The interplay between DNA damage and autophagy in lung cancer: A mathematical study

Sarmah, Dipanka Tanu; Bairagi, Nandadulal; Chatterjee, Samrat

doi:10.1016/j.biosystems.2021.104443

Cited by 6 publications

(1 citation statement)

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“…Research has shown that uncontrolled mutations and disruptions in genomic stability may lead to tumor heterogeneity and polymorphism, potentially activating anti-tumor immune responses [10]. This includes the mutation of key genes within tumor cells, stalling of the replication fork, and the induction of autophagy and apoptosis [11]. Autophagy is a highly conserved physiological process in eukaryotic cells.…”

Section: Introductionmentioning

confidence: 99%

CS-6-Induced p62 Accumulation Exacerbates DNA Damage: A Mechanistic Insight into Colorectal Cancer Suppression

Gong,

Cui,

Dong

et al. 2023

Preprint

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Gamabufotalin (CS-6), a bufadienolide derived from Chansu, its role in colorectal cancer (CRC) remains unexplored. CS-6 treatment significantly inhibited CRC SW620 and DLD1 cell viability and colony formation in vitro. Furthermore, CS-6 treatment-induced DNA damage and cell cycle arrest in SW620 and DLD1 cells. Proteomics analysis and the western blot assay revealed that CS-6 treatment upregulated p62 expression, an autophagic substrate involved in the regulation of DNA double-strand damage repair. Knockdown of p62 in this study significantly alleviated CS-6-induced DNA damage and the downregulation of cyclin expression in SW620 and DLD1 cells. Additionally, the results indicated increased expression of microtubule-associated protein 1A/1B light chain 3B (LC3B) and reduced binding between B-cell lymphoma-2 (Bcl2) and beclin-1, suggesting that CS-6 treatment activated early-stage autophagy in CRC cells. However, inhibition of late-stage autophagy and autophagy-related protein 5 (ATG5) with chloroquine and si-ATG5, respectively, further indicated that CS-6-induced autophagy defects led to p62 accumulation, exacerbated cell proliferation inhibition, and aggravated DNA damage. In conclusion, this study suggests that CS-6 may exert its anti-tumor effects in CRC by inducing autophagy defects, resulting in p62 accumulation and DNA damage.

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Section: Introductionmentioning

confidence: 99%