Hemocyanin (HMC) has been shown to participate in multiple roles of immune defence. In this study, we investigated the antiproliferative effect and underpinning mechanism of HMC from Litopenaeus vannamei in vitro. Sulforhodamine B (SRB) assay indicated that HMC could dramatically inhibit the growth of HeLa cells, but not 293T cells under the same conditions. Moreover, typical morphological features of apoptosis in HeLa cells including the formation of apoptotic body-like vesicles, chromatin condensation and margination were observed by using 4, 6-diamidino-2- phenylindole dihydrochloride (DAPI) staining and fluorescence analysis. An apoptotic DNA ladder from 180 to 300 bp was also detected. Furthermore, 10 variation proteins associated with apoptosis pathway, viz. G3PDH isoforms 1/2 (G3PDH1/2), aldosereductase, ectodemal dysplasia receptor associated death receptor domain isoform CRA_a (EDARADD), heat shock 60kD protein 1 variant 1 (HSP60), heat shock 70kDa protein 5 precursor (HSP70), heat shock protein 90kDa beta member 1 precursor (HSP90), 14-3-3 protein ζ/δ, Ran and ubiquitin activating enzyme E1(UBE1), were identified from HMC-treated HeLa cells by the proteomic and quantitative real-time RT-PCR strategies. Importantly, the reactive oxygen species (ROS), mitochondrial membrane potential (Δψm) and caspase-9/3 activities were changed significantly in HMC-treated HeLa cells. Together, the data suggests that L. vannamei HMC mediates antiproliferative properties through the apoptosis mechanism involving the mitochondria triggered pathway.
Antimicrobial peptides play important roles in the immune response to pathogens and tumor cells; for this reason, they are being exploited for therapeutic use. In this study, we describe a Litopenaeus vannamei hemocyanin-derived peptide, denoted B11, which shares similar features with other anticancer peptides and attenuates the proliferation of cancer cells. Cell viability assay revealed that B11 significantly inhibited the proliferation of human cervical (HeLa), human hepatocellular carcinoma (HepG2), and human esophageal cancer (EC109) cancer cell lines, but not normal liver cell lines (T-antigen-immortalized human liver epithelial (THLE) cells or THLE-3), by inducing morphological changes, nuclear condensation, and margination, features which are indicative of apoptosis. Besides, peptide B11-induced apoptosis was confirmed by isothiocyanate-labeled Annexin V/propidium iodide (Annexin V-FITC/PI) double staining of HeLa cells. Moreover, cell uptake studies, confocal microscopy, and Western blot analysis revealed that rhodamine-labeled B11 permeated HeLa cells and localized to the mitochondria, causing mitochondria dysfunction through lost mitochondrial membrane potential, which consequently triggered the induction of apoptosis. Increased expression levels of caspase-9, caspase-3, and Bax (Bcl-2-associated X) proteins, coupled with a decrease in Bcl-2 (B-cell lymphoma 2) protein, confirmed that peptide B11 induced apoptosis via the mitochondrial pathway. Thus, the hemocyanin-derived peptide, B11, inhibits the proliferation of cancer cells by causing mitochondrial dysfunction and inducing apoptotic cell death, for which reason it could be explored as an anticancer peptide.
Disulfidptosis is a novel form of cell death triggered by disulfide stress that may have important implications for breast cancer (BC) pathogenesis. Nevertheless, studies identifying disulfidptosis-associated long non-coding RNAs (lncRNAs) in BC have not been reported. This study aimed to investigate the prognostic potential of disulfidptosis-related lncRNAs in BC.
Breast cancer is a prevalent malignancy that poses a serious threat to women’s health. Lifestyle modifications can alter the risk of breast cancer. Walking is a common lifestyle behaviour, but its impact on breast cancer remains unclear. We conducted a Mendelian randomisation (MR) study to explore this issue. Independent genetic variants closely associated with usual walking speed were selected as instrumental variables from publicly available genome-wide association studies (GWAS) databases. Genetic data on the estrogen receptor (ER) status of breast cancer and breast cancer were obtained from a large-scale GWAS meta-analysis. Inverse variance-weighted regression analysis revealed that brisk walking speed was associated with a lower risk of breast cancer [OR = 0.69; 95%CI = (0.54, 0.88); P = 0.006] and lower risk of ER− breast cancer [OR = 0.60; 95%CI = (0.38, 0.91); P = 0.018]. However, walking speed was not associated with the risk of ER + breast cancer [OR = 0.92; 95%CI = (0.70, 1.25); P = 0.641]. MR-Egger intercept and MR-PRESSO tests did not reveal significant levels of pleiotropy or heterogeneity, respectively. Sensitivity analyses also confirmed the robustness of the results. Our study provides strong evidence that faster walking speeds may reduce the risk of breast cancer and that a more widespread adoption of moderate or high-intensity exercise may be effective in reducing women’s health risks.
Abstract Purpose: Disulfidptosis, a novel form of cell death triggered by disulfide stress, could have significant implications in breast cancer (BC) pathogenesis. Despite this, the identification of disulfidptosis-related lncRNAs in BC remains has not been reported. Therefore, this study aimed to examine the prognostic potential of disulfidptosis-associated lncRNAs in BC. Methods: RNA-seq data and clinical information of BC patients were obtained from the TCGA database. Co-expression analysis was performed to identify disulfidptosis-associated lncRNAs. Subsequently, a risk signature was developed through univariate Cox and LASSO analyses, and its predictive ability was validated. Additionally, the association between the risk signature and immune cell infiltration, immune function, tumor mutational burden (TMB）, and immune checkpoints was investigated. Finally, potential anticancer drugs associated with the risk signatures were predicted. Results: A 10-lncRNA signature was established to stratify BC patients into high-risk and low-risk groups, where the high-risk group showed an unfavorable prognosis. This signature served as an independent prognostic factor in BC patients. Notably, the two subgroups displayed distinct mutation gene profiles, and the risk score exhibited a significant correlation with TMB. Furthermore, ssGSEA and immune checkpoint analysis revealed a significant association between the predictive signature and the immune status of BC patients. Finally, 55 potential anticancer drugs associated with the signature were identified. CONCLUSIONS: We successfully established an independent prognostic signature of disulfidptosis-related lncRNAs in BC patients. This signature provides a solid basis for future investigations into the functional significance of disulfidptosis-associated lncRNAs in breast cancer.
Hemocyanin is a multifunctional glycoprotein, which also plays multiple roles in immune defense. While it has been demonstrated that hemocyanin from some mollusks can induce potent immune response and is therefore undergoing clinical trials to be used in anti-tumor immunotherapy, little is currently known about how hemocyanin from arthropods affect tumors. In this study we investigated the anti-tumor activity of hemocyanin from Litopenaeus vannamei on Sarcoma-180 (S180) tumor-bearing mice model. Eight days treatment with 4mg/kg bodyweight of hemocyanin significantly inhibited the growth of S180 up to 49% as compared to untreated. Similarly, histopathology analysis showed a significant decrease in tumor cell number and density in the tissues of treated mice. Moreover, there was a significant increase in immune organs index, lymphocyte proliferation, NK cell cytotoxic activity and serum TNF-α level, suggesting that hemocyanin could improve the immunity of the S180 tumor-bearing mice. Additionally, there was a significant increase in superoxide dismutase (SOD) activity and a decrease in the level of malondialdehyde (MDA) in serum and liver, which further suggest that hemocyanin improved the anti-oxidant ability of the S180 tumor-bearing mice. Collectively, our data demonstrated that L. vannamei hemocyanin had a significant antitumor activity in mice.
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