Dataset Information

Zinc oxide nanosphere for hydrogen sulfide scavenging and ferroptosis of colorectal cancer.

ABSTRACT:

Background

Colorectal cancer is a common malignancy occurring in the digestive system and ranks second in cancer mortality worldwide. In colorectal cancer, hydrogen sulfide (H₂S) is selectively upregulated, resulting in the further exacerbation of the disease. Therefore, the clearance of H₂S and the regulation of the enzymes on the H₂S pathways are of great significance for colorectal cancer therapy.

Methods

Here, we investigated the H₂S content in various clinical tumor tissues from patients and confirmed that overproduced concentration of H₂S in colorectal cancer. Accordingly, we developed an H₂S-responsive nanoplatform based on zinc oxide coated virus-like silica nanoparticles (VZnO) for the therapy of colorectal cancer.

Results

Owing to its excellent H₂S scavenging ability, VZnO could effectively reduce H₂S content in colorectal cancer to prohibit the growth of CT26 and HCT116 colorectal cancer cells. Moreover, the removal of H₂S in colorectal cancer also leads to tumor inhibition through activating ferroptosis, a non-apoptotic form of cell death. The biosafety-related toxicological and pathological analysis confirmed the low toxicity and high safety of VZnO in colorectal cancer treatment. Furthermore, as an H₂S-responsible nanosystem, VZnO appears to have no therapeutic effect on other non H₂S rich cancers, such as the 4T1 breast cancer model.

Conclusions

We anticipate that the H₂S-depletion-induced ferroptosis strategy using zinc oxide-based nanomaterials would provide insights in designing nanomedicines for colorectal cancer-target theranostics and may offer clinical promise.

SUBMITTER: Pan X

PROVIDER: S-EPMC8626909 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Nitric oxide (NO) and hydrogen sulfide (H2S) are novel signaling molecules, which participate in plant growth, development, and response to stress. In this study root-irrigation with 0.15 mM sodium nitroprusside (SNP, NO donor) up-regulated gene expression of L-CYSTEINE DESULFHYDRASE1 (LCD1), activities of L-cysteine desulfhydrase (LCD) and D-cysteine desulfhydrase (DCD), as well as an endogenous H2S level, compared to control seedlings. The SNP-up-regulated effects were enhanced by 0.5 mM sodium hydrosulfide (NaHS, H2S donor), but weakened by NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) and H2S scavenger hypotaurine (HT) alone. NaHS had no significant effect on gene expression and activity of nitrate reductase (NR, a NO candidate producing enzyme). These data indicate that NO could trigger the LCD/H2S signaling pathway in maize seedlings. To further investigate the effect of NO and H2S crosstalk on thermotolerance in maize seedlings, thermotolerance parameters and reactive oxygen species (ROS)-scavenging system were estimated. The results show that SNP increased survival rate and tissue viability, decreased malondialdehyde (MDA) accumulation, and electrolyte leakage in maize seedlings under heat stress (HS), implying NO could improve thermotolerance in maize seedlings. The NO-improved thermotolerance was impaired by H2S inhibitor DL-propargylglycine (PAG) and scavenger HT alone. Similarly, SNP up-regulated the gene expression of DEHYDROASCORBATE REDUCTASE (DHAR) and GLUTATHIONE REDUCTASE1 (GR1); activities of ascorbate peroxidase, glutathione reductase, and catalase; as well as levels of ascorbic acid, glutathione, flavonoids, carotenoids, and total phenols. SNP also reduced hydrogen peroxide and superoxide radical accumulation in maize seedlings under HS compared to the control. The effects of SNP on ROS and their scavenger system were weakened by PAG and HT alone. These data hint that NO could evoke thermotolerance in maize seedlings by triggering the LCD/H2S signaling pathway, and the ROS-scavenging system played a key role in the NO and H2S crosstalk-evoked thermotolerance.