Ilicicolin C suppresses the progression of prostate cancer by inhibiting PI3K/AKT/mTOR pathway.

Aberrant activation of the PI3K/AKT pathway is a driving factor in the development of prostate cancer. Therefore, inhibiting the function of the PI3K/AKT signaling pathway is a strategy for the treatment of prostate cancer. Ilicicolin C is an ascochlorin derivative isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501. Which has anti-inflammatory activity, but its activity against prostate cancer has not yet been elucidated. MTT assay, plate clone-formation assay, flow cytometry and real-time cell analysis technology were used to detect the effects of ilicicolin C on cell viability, proliferation, apoptosis and migration of prostate cancer cells. Molecular docking software and surface plasmon resonance technology were used to analyze the interaction between ilicicolin C and PI3K/AKT proteins. Western blot assay was performed to examine the changes in protein expression. Finally, QikProp software was used to simulate the process of ilicicolin C in vivo, and a zebrafish xenograft model was used to further verify the anti-prostate cancer activity of ilicicolin C in vivo. Ilicicolin C showed cytotoxic effects on prostate cancer cells, with the most significant effect on PC-3 cells. Ilicicolin C inhibited proliferation and migration of PC-3 cells. It could also block the cell cycle and induce apoptosis in PC-3 cells. In addition, ilicicolin C could bind to PI3K/AKT proteins. Furthermore, ilicicolin C inhibited the expression of PI3K, AKT and mTOR proteins and could also regulate the expression of downstream proteins in the PI3K/AKT/mTOR signaling pathway. Moreover, the calculations speculated that ilicicolin C was well absorbed orally, and the zebrafish xenograft model confirmed the in vivo anti-prostate cancer effect of ilicicolin C. Ilicicolin C emerges as a promising marine compound capable of inducing apoptosis of prostate cancer cells by counteracting the aberrant activation of PI3K/AKT/mTOR, suggesting that ilicicolin C may be a viable candidate for anti-prostate cancer drug development. These findings highlight the potential of ilicicolin C against prostate cancer and shed light on its mechanism of action.

Novel Metabolites from the Marine-Derived Fungus Peniophora sp. SCSIO41203 Show Promising In Vitro Antitumor Activity as Methuosis Inducers in PC-3 Cells.

Two new cytochalasin derivatives, peniotrinins A (1) and B (2), three new citrinin derivatives, peniotrinins C-E (4, 5, 7), and one new tetramic acid derivative, peniotrinin F (12), along with nine structurally related known compounds, were isolated from the solid culture of Peniophora sp. SCSIO41203. Their structures, including the absolute configurations of their stereogenic carbons, were fully elucidated based on spectroscopic analysis, quantum chemical calculations, and the calculated ECD. Interestingly, 1 is the first example of a rare 6/5/5/5/6/13 hexacyclic cytochalasin. We screened the above compounds for their anti-prostate cancer activity and found that compound 3 had a significant anti-prostate cancer cell proliferation effect, while compounds 1 and 2 showed weak activity at 10 µM. We then confirmed that compound 3 exerts its anti-prostate cancer effect by inducing methuosis through transmission electron microscopy and cellular immunostaining, which suggested that compound 3 might be first reported as a potential anti-prostate methuosis inducer.

Huaier enhances the tumor-killing effect and reverses gemcitabine-induced stemness by suppressing FoxM1.

BACKGROUND: Gemcitabine is the first-line chemotherapy drug that can easily cause chemotherapy resistance. Huaier is a traditional Chinese medicine and shows an antitumor effect in pancreatic cancer, but whether it can enhance the gemcitabine chemotherapeutic response and the potential mechanism remain unknown. PURPOSE: This study was performed to explore the effect of Huaier in promoting the tumor-killing effect of gemcitabine and elucidate the possible mechanism in pancreatic cancer. METHODS: Cell Counting Kit-8 assays and colony formation assays were used to detect proliferation after different treatments. Protein coimmunoprecipitation was applied to demonstrate protein interactions. Nuclear protein extraction and immunofluorescence were used to confirm the intracellular localization of the proteins. Western blotting was performed to detect cell proliferation-related protein expression or cancer stem cell-associated protein expression. Sphere formation assays and flow cytometry were used to assess the stemness of pancreatic cancer cells. The in vivo xenograft model was used to confirm the inhibitory effect under physiological conditions, and immunohistochemistry was used to detect protein expression. RESULTS: Huaier suppressed the proliferation and stem cell-like properties of pancreatic cancer cells. We found that Huaier suppressed the expression of forkhead box protein M1 (FoxM1). In addition, Huaier inhibited FoxM1 function by blocking its nuclear translocation. Treatment with Huaier reversed the stemness induced by gemcitabine in a FoxM1-dependent manner. Furthermore, we verified the above results by an in vivo study, which reached the same conclusion as those in vitro. CONCLUSION: Overall, this study illustrates that Huaier augments the tumor-killing effect of gemcitabine through suppressing the stemness induced by gemcitabine in a FoxM1-dependent way. These results indicate that Huaier can be applied to overcome gemcitabine resistance.

Impact of carbon emission trading system on green technology innovation of energy enterprises in China.

China proposed establishing a carbon emission trading market in its 12th Five-Year Plan to reduce carbon dioxide emissions through market mechanisms, promote the development of science and technology and help China become an environment-friendly country. To examine the impact of carbon emission trading on green technology innovation in Chinese energy enterprises, data from 1993 to 2020 were collected from 494 A-share-listed energy enterprises. Enterprises located in the pilot area of carbon emissions trading were assigned to the treatment group, while those in the non-pilot area were assigned to the control group. The propensity-score-matching method was utilized to match the treatment group with the control group, and the resulting samples were used as the actual sample data. The difference-in-differences method was then employed to assess the net impact of carbon emission trading and investigate its effect on green technology innovation in energy enterprises. This empirical study suggested that carbon emission trading has a positive impact on green technology innovation in energy enterprises, particularly state-owned ones. Larger enterprises are more willing to engage in green technological innovation than small enterprises. Furthermore, when faced with a carbon emission trading system, 'mature' companies tend to pay more attention to green technology innovation than younger enterprises do. This study puts forward policy measures for establishing a national-level carbon emission market in China in the future.

Recent advances in flavonoid compounds for the treatment of prostate cancer.

Prostate cancer is a malignant epithelial tumor of the prostate gland and is the most common malignant tumor of the male genitourinary system. Pharmacological therapies, including chemotherapy and androgen deprivation therapy, play a key role in the treatment of prostate cancer. However, drug resistance and side effects limit the use of these drugs and so there is a need for new drug therapies for prostate cancer patients. Flavonoids, with their wide range of sources and diverse biological activities, have attracted much attention in the field of anti-tumor drug screening. In 2016, at least 58 flavonoids were reported to have anti-prostate cancer activity. In recent years, six additional flavonoid compounds have been found to have anti-prostate cancer potential. In this review, we have collected a large amount of evidence on the anti-prostate cancer effects of these six flavonoids, including a large number of cellular experiments and a small number of preclinical animal experiments. In addition, we predicted their drug-forming properties using Schrödinger's QikProp software and ADMETlab due to the lack of in vivo pharmacokinetic data for the six compounds. In conclusion, this review has fully confirmed the anti-prostate cancer effects of these six flavonoids, summarized their mechanisms of action and predicted their druggability. It provides a reference for the further development of these compounds into anti-prostate cancer drugs.

Chronic low-dose deltamethrin exposure induces colon injury and aggravates DSS-induced colitis via promoting cellular senescence.

OBJECTIVE: Deltamethrin (DLM) is a commonly used insecticide, which is harmful to many organs. Here, we explored the effects of chronic low-dose DLM residues on colon tissue and its potential mechanism. METHODS: The mice were given long-term low-dose DLM by intragastric administration, and the body weights and disease activity index (DAI) scores of the mice were regularly recorded. The colon tissues were then collected for hematoxylin-eosin, immunofluorescence and immunohistochemistry staining. Besides, the RNA sequencing was performed to explore the potential mechanism. RESULTS: Our results showed that long-term exposure to low-dose DLM could cause inflammation in mice colon tissue, manifested as weight loss, increased DAI score, increased apoptosis of colonic epithelial cells, and increased infiltration of inflammatory cells. However, we observed that after long-term exposure to DLM and withdrawal for a period of time, although apoptosis was restored, the recovery of colon inflammation was not ideal. Subsequently, we performed RNA sequencing and found that long-term DLM exposure could lead to the senescence of some cells in mice colon tissue. The results of staining of cellular senescence markers in colon tissue showed that the level of cellular senescence in the DLM group was significantly increased, and the p53 signalling related to senescence was also significantly activated, indicating that cellular senescence played a key role in DLM-induced colitis. We further treated mice with quercetin (QUE) after long-term DLM exposure, and found that QUE could indeed alleviate DLM-induced colitis. In addition, we observed that long-term accumulation of DLM could aggravate DSS-induced colitis in mice, and QUE treatment could reverse this scenario. CONCLUSION: Continuous intake of DLM caused chronic colitis in mice, and the inflammation persisted even after discontinuation of DLM intake. This was attributed to the induction of cellular senescence in colon tissue. Treatment with QUE alleviated DLM-induced colitis by reducing cellular senescence. Long-term DLM exposure also aggravated DSS-induced colitis, which could be mitigated by QUE treatment.

Research on optimal operation of cascade pumping stations based on an improved sparrow search algorithm.

For the low efficiency and large loss of cascade pumping stations, aiming to maximize system efficiency, an optimized scheduling model of cascade pumping stations is established with consideration of multiple constraints, and the optimal scheduling method based on the improved sparrow search algorithm (BSSA) is proposed. The BSSA is initialized by the Bernoulli chaotic map to solve the insufficient initial diversity of the sparrow search algorithm (SSA). The random boundary strategy is introduced to avoid local optimum when dealing with the scheduling problem of pumping stations. The performance and improvement strategy of BSSA are verified by eight benchmark functions. Results show that BSSA has better convergence accuracy and faster speed. BSSA is applied to a three-stage pumping station considering three flow conditions, and compared with the current scheme, particle swarm optimization and genetic algorithm optimization schemes, the operation efficiency of SSA can be increased by 0.72-0.96%, and operation cost can be reduced by ¥263,000/a-¥363,300/a. On this basis, the improvement of 0.04-0.30% and ¥14,800/a-¥109,900/a can be further achieved by the BSSA, which confirms the feasibility and effectiveness of BSSA to solve the pumping station optimal scheduling problem. The findings present useful reference for the optimized scheduling of pumping station system.

Plasma-Activated Solutions Mitigates DSS-Induced Colitis via Restoring Redox Homeostasis and Reversing Microbiota Dysbiosis.

Ulcerative colitis is a chronic disease that increases the risk of developing colorectal cancer. Conventional medications are limited by drug delivery and a weak capacity to modulate the inflammatory microenvironment. Further, gut microbiota dysbiosis caused by mucosal damage and dysregulated redox homeostasis leads to frequent recurrence. Therefore, promoting mucosal healing and restoring redox homeostasis is considered the initial step in treating ulcerative colitis. Plasma-activated solutions (PAS) are liquids rich in various reactive nitrogen species (RNS) and reactive oxygen species (ROS) and are used to treat multiple diseases. However, its effect on ulcerative colitis remains to be examined. Therefore, using a DSS-induced mice colitis model, it is found that PAS has the potential to treat colitis and prevent its recurrence by promoting intestinal mucosal repair, reducing inflammation, improving redox homeostasis, and reversing gut microbiota dysbiosis. Further, an equipment is designed for preparing PAS without using nitrogen; however, after treatment with the Nitro-free PAS, the therapeutic effect of PAS is significantly weakened or even lost, indicating that RNS may be the main mediator by which PAS exerts its therapeutic effects. Overall, this study demonstrates the treatment of ulcerative colitis as a novel application of PAS.

Combination of Kaempferol and Docetaxel Induces Autophagy in Prostate Cancer Cells In Vitro and In Vivo.

Docetaxel is a first-line chemotherapy drug used to treat advanced prostate cancer, but patients who have used it often face the challenges of drug resistance and side effects. Kaempferol is a naturally occurring flavonol; our previous studies have confirmed that it has excellent anti-prostate activity. To investigate the anti-prostate cancer effects of docetaxel in combination with kaempferol, we conducted experiments at the cellular and whole-animal level. Plate cloning assays showed that the combination of docetaxel and kaempferol had a synergistic effect in inhibiting the proliferation of prostate cancer cells. The combination of these two compounds was found to induce autophagy in prostate cancer cells via transmission electron microscopy, and changes in the expression of autophagy-related proteins via Western blot assays also confirmed the occurrence of autophagy at the molecular level. We also confirmed the anti-prostate cancer effect of docetaxel in combination with kaempferol in vivo by establishing a mouse xenograft prostate cancer model. Autophagy-related proteins were also examined in mouse tumor tissues and verified the presence of autophagy in mouse tumor tissues. The above cellular and animal data suggest that docetaxel in combination with kaempferol has significant anti-prostate cancer effects and that it works by inducing autophagy in cells.

Chronic exposure to low-dose deltamethrin can lead to colon tissue injury through PRDX1 inactivation-induced mitochondrial oxidative stress injury and gut microbial dysbiosis.

OBJECTIVE: To date, it is unclear whether deltamethrin (DLM) intake causes damage to colon tissue. Hence, in this study, we aimed to clarify the effect of long-term exposure to low-dose DLM on colon tissues, and its potential mechanisms. METHODS: Mice were treated with DLM (0.2 mg/kg/day) or DLM combined with N-acetyl-l-cysteine (NAC) (50 mg/kg/day) for 8 weeks. Human colon cancer cells (HCT-116) were treated with DLM (0, 25, 50, or 100 µM), NAC (2 mM), or overexpression plasmids targeting peroxiredoxin 1 (PRDX1) for 48 h. DLM was detected using a DLM rapid detection card. Colon injury was evaluated using haematoxylin and eosin staining and transmission electron microscopy. Apoptosis was determined using immunofluorescence staining (IF), western blotting (WB) and flow cytometry (FC) assays. MitoTracker, JC-1, and glutathione (GSH) detection were used to detect mitochondrial oxidative stress. Intestinal flora were identified by 16 S rDNA sequencing. RESULTS: DLM accumulation was detected in the colon tissue and faeces of mice following long-term intragastric administration. Interestingly, our results showed that, even at a low dose, long-term intake of DLM resulted in severe weight loss and decreased the disease activity index scores and colon length. The results of IF, WB, and FC showed that DLM induced apoptosis in the colon tissue and cells. MitoTracker, JC-1, and GSH assays showed that DLM increased mitochondrial stress in colonic epithelial cells. Mechanistic studies have shown that increased mitochondrial stress and apoptosis are mediated by PRDX1 inhibition. Further experiments showed that PRDX1 overexpression significantly reduced DLM-induced oxidative stress injury and apoptosis. In addition, we observed that chronic exposure to DLM altered the composition of the intestinal flora in mice, including an increase in Odoribacter and Bacteroides and a decrease in Lactobacillus. The gut microbial richness decreased after DLM exposure in mice. Supplementation with NAC both in vivo and in vitro alleviated DLM-induced oxidative stress injury, colonic epithelial cell apoptosis, and gut microbial dysbiosis. CONCLUSION: Chronic exposure to DLM, even at small doses, can cause damage to the colon tissue, which cannot be ignored. The production and use of pesticides such as DLM should be strictly regulated during agricultural production.

Targeting androgen receptor in glioblastoma.

Glioblastomas are primary brain tumors that originate from glial stem cells or progenitor cells. There is a large difference in the incidence of glioblastoma between males and females. Studies revealed that the gender differences in the tumor may be attributable to the androgen receptor signaling axis. The incidence rate of glioblastoma in men is higher than that in women. Aberrant activation of the androgen receptor signaling pathway, or interactions between the androgen receptor signaling axis and other signaling axes promote the development of glioblastoma. Therefore, targeting the androgen receptor holds promise as a therapeutic approach for glioblastoma. This review investigates the dynamics of drug research into the treatment of glioblastoma by targeting the androgen receptor. The first finding in line with expectations is that androgen receptor antagonists, represented by enzalutamide, have been studied and shown to have anti-glioblastoma effects. In addition, it was found that the combination of 5-alpha reductase inhibitors and androgen receptor antagonists resulted in better therapeutic outcomes than each of them alone. Similar results were obtained with the combination of an epidermal growth factor receptor inhibitor and an androgen receptor antagonist. In addition, four small molecule compounds have been shown to exert significant anti-glioblastoma effects by directly or indirectly targeting the androgen receptor. Expectantly, one of these small molecules, seviteronel, progressed to the phase II clinical trial stage. These findings suggest that targeting the androgen receptor for glioblastoma may be a promising therapeutic option.

Dankasterone A induces prostate cancer cell death by inducing oxidative stress.

Oxidative stress plays a dual role in tumor survival, either promoting tumor development or killing tumor cells under different conditions. Dankasterone A is a secondary metabolite derived from the fungus Talaromyces purpurogenu. It showed good potential in a screen for anti-prostate cancer compounds. In this study, MTT results showed dankasterone A was cytotoxic to prostate cancer cells, with an IC50 of 5.10 µM for PC-3 cells and 3.41 µM for 22Rv1 cells. Further studies, plate cloning assays and real-time cell analysis monitoring showed that dankasterone A significantly inhibited clonal colony formation and cell migration in 22Rv1 and PC-3 cells. In addition, flow cytometry results showed that dankasterone A induced apoptosis in prostate cancer cells while having no impact on cell cycle distribution. At the molecular level, Protein microarray experiments and western blot assays revealed that dankasterone A specifically and dramatically upregulated HO-1 protein expression; and the results of cell fluorescence staining showed that dankasterone A induced overexpression of reactive oxygen species in 22Rv1 and PC-3 cells. Taken together, dankasterone A induced prostate cancer cells to undergo intense oxidative stress, which resulted in the production of large amounts of HO-1 and the release of large amounts of reactive oxygen species, leading to apoptosis of prostate cancer cells, ultimately resulting in the inhibition of both cell proliferation and migration. We also validated the anti-prostate cancer effects of dankasterone A in vivo in a zebrafish xenograft tumor model. In conclusion, dankasterone A has the potential to be developed as an anti-prostate cancer drug.

Bioactive Molecules against Rheumatoid Arthritis by Suppressing Pyroptosis.

Rheumatoid arthritis is an inflammatory disease, and pyroptosis is a form of death associated with an inflammatory response. Pyroptosis, which occurs in synovial and osteoblastic cells, can exacerbate the development of rheumatoid arthritis. The inhibition of pyroptosis of these cells can, therefore, clearly be used as a therapeutic strategy against rheumatoid arthritis. Here, we have summarized the current status of progress in the treatment of rheumatoid arthritis by targeting cellular pyroptosis. We have identified seven compounds, including a cyclic RNA, a microRNA, a peptide, and a cytokine (protein), that may influence the progression of rheumatoid arthritis by regulating the initiation of pyroptosis. All of these compounds have been shown to have anti-rheumatoid effects in vitro and/or in vivo and have the potential to be developed as anti-rheumatoid agents. These findings may help to accelerate the development of anti-rheumatoid arthritis drugs.

Bioactive secondary metabolites isolated from the soft coral derived Penicillium sp. SCSIO 41038.

Chemical investigation of the Penicillium sp. SCSIO 41038 led to the isolation and characterization of one new cyclopiazonic acid-type alkaloid, speradine I (1), and one new phloroglucinol derivative, speradine J (8), along with 13 known compounds. Their structures were determined on the basis of extensive spectroscopic analysis, and by a comparison with data from the literature. All the compounds were evaluated for their antitumor (22Rv1 and PC-3) and enzyme inhibitory activity against acetylcholinesterase (AChE) in vitro.

MAX transcriptionally enhances PD-L1 to inhibit CD8+ T cell-mediated killing of lung adenocarcinoma cells.

Immune checkpoint blockade (ICB) therapies, such as monoclonal antibodies against the PD-1/PD-L1 immune checkpoint pathway, have been a major breakthrough in the treatment of lung cancer especially lung adenocarcinoma (LUAD), but their effectiveness is limited. High expression of PD-L1 in tumor cells is one of the key reasons evading immune surveillance, yet the mechanisms that regulate PD-L1 expression are not fully understood. By analyzing the chromatin immunoprecipitation sequencing data of MYC-associated X-factor (MAX) based on lung cancer cell lines, we found that the transcriptional regulator MAX is able to bind to the promoter region of the PD-L1 gene. Further, we performed several molecular biology experiments to determine that MAX promotes PD-L1 transcription in LUAD cells, which in turn assists LUAD cells to evade killing by CD8+ T cells, an effect that can be reversed by anti-PD-L1 antibody. In LUAD, the expression of MAX is positively correlated with PD-L1 and the infiltration of CD8+ T cells. Importantly, we further identified that high expression of the MAX/PD-L1 axis is associated with poor overall survival and fist progression of patients with LUAD. Thus, this study sheds light on the mechanism by which MAX inhibits CD8+ T cell-mediated killing of LUAD cells by activating PD-L1 transcription, and MAX may serve as a potential combinatorial target for ICB therapies that block the PD-1/PD-L1 pathway in LUAD.

Structurally various p-terphenyls with neuraminidase inhibitory from a sponge derived fungus Aspergillus sp. SCSIO41315.

Guided by Global Natural Products Social molecular networking, 14 new p-terphenyl derivatives, asperterphenyls A-N (1-14), together with 20 known p-terphenyl derivatives (15-34), were obtained from a sponge derived fungus Aspergillus sp. SCSIO41315. Among them, new compounds 2-8 and 15-17 were ten pairs of enantiomers. Comprehensive methods such as chiral-phase HPLC analysis, ECD calculations and X-ray diffraction analysis were applied to determine the absolute configurations. Asperterphenyls B (2) and C (3) represented the first reported natural p-terphenyl derivatives possessing a dicarboxylic acid system. Asperterphenyl A (1) displayed neuraminidase inhibitory activity with an IC50 value of 1.77 ± 0.53 µM and could efficiently inhibit infection of multiple strains of H1N1 with IC50 values from 0.67 ± 0.28 to 1.48 ± 0.60 µM through decreasing viral plaque formation in a dose-dependent manner, which suggested that asperterphenyl A (1) might be exploited as a potential antiviral compound in the pharmaceutical fields.

Green finance: how can it help Chinese power enterprises transition towards carbon neutrality.

China's power sector must cut its carbon emissions by 90% by 2060 to become carbon neutral. Green finance, as a crucial link in sustainable development, is garnering attention for its role as a mechanism for the green transformation of power enterprises. The process of green transformation development is highly challenging and requires a lot of financial support. This paper discusses the design of schemes for fiscal and financial support mechanisms for the green transformation of power enterprises, financing mechanisms to strengthen green finance, and financial support mechanisms to promote carbon trading. The utilization of green finance by power enterprises is assessed after defining the impact routes of green finance on clean energy power firms and highly polluting power firms. Using the SBM-GML model with variable returns to scale, the dynamic change of the use efficiency of green finance in power enterprises is calculated. At the same time, the enterprises are classified by power generation methods, and the changes in the power generation structure of power enterprises are analyzed. Compared with 2014, the total power generation in 2021 increased by 59.14%, wind power generation increased by 170.78%, and photovoltaic power generation increased by 974.31%. Hydropower, by contrast, grew by 94.14% and thermal power by only 45.09%. The results show that the evolution of total factor productivity and green total factor productivity of the 24 listed electric power enterprises is "M" shaped, that the main cause of the fluctuation is the serious phenomenon of "Triple Abandonments" of wind, light, and water in China's power industry, and that the main means to improve total factor productivity and green total factor productivity of the power industry is to improve green power production technology. Classified by power generation mode, it is found that hybrid power generation enterprises have the highest average efficiency value, followed by wind power generation. China's power enterprises are still dominated by thermal power generation; before the "Double Carbon" target, green power generation enterprises have not significantly improved the efficiency of green finance. The series of green finance mechanisms of action described in this study have a beneficial impact on the green transition of energy, according to a predictive analysis that combines existing policy objectives and practical mechanisms. Even without green financial support, the composition of China's major clean energy sources will account for 86.85% of total electricity generation by 2060, while with green financial support, coal generation will fall to 0% around 2056, with hydroelectric, wind, and photovoltaic generation accounting for 11.81%, 50.00%, and 38.19% of electricity sources, respectively, and green finance will drive important technological changes, and the "Triple Abandonments" phenomenon will be fundamentally corrected. Finally, countermeasures and suggestions for the healthy development of green finance in power enterprises are proposed based on the findings of the study.

Phytochemicals Targeting Ferroptosis: Therapeutic Opportunities and Prospects for Treating Breast Cancer.

Ferroptosis, a recently discovered iron-dependent regulated cell death, has been implicated in the therapeutic responses of various cancers including breast cancer, making it a promising therapeutic target to manage this malignancy. Phytochemicals are conventional sources for medication development. Some phytochemicals have been utilized therapeutically to treat cancers as pharmaceutic agents or dietary supplements. Intriguingly, a considerable number of antitumor drugs derived from phytochemicals have been proven to be targeting ferroptosis, thus producing anticancer effects. In this review, we provide a short overview of the interaction between core ferroptosis modulators and breast cancer, illustrating how ferroptosis affects the destiny of breast cancer cells. We also systematically summarize the regulatory effects of phytochemicals on ferroptosis and emphasize their clinical applications in breast cancer suppression, which may accelerate the development of their therapeutic use in breast cancer.

Huaier suppresses pancreatic cancer progression via activating cell autophagy induced ferroptosis.

Purpose: The anti-tumour effect of Huaier has been demonstrated in a variety of tumours. Ferroptosis is a newly identified type of programmed cell death accompanied by the accumulation of reactive oxygen species (ROS) and iron in cells and plays a key role in the therapeutic process against malignant tumours. We aimed to explore the potential therapeutic role of Huaier in pancreatic cancer and uncover the relationship between Huaier and ferroptosis. Methods: CCK8 and colony formation assays were used to determine the proliferation of pancreatic cancer cells (PCs). The levels of cellular ROS were analysed by a fluorescence probe, and the accumulation of cellular iron was showed by Prussian blue staining. The autophagosomes and mitochondrial morphology were characterised by transmission electron microscopy (TEM). The levels of intracellular glutathione (GSH) and lipid peroxidation were measured by the corresponding kits. Results: The growth inhibitory effect of Huaier on PCs was concentration- and time-dependent, but this effect was significantly attenuated by ferroptosis inhibitors. In addition, Huaier effectively inhibited the GSH-GPX4 antioxidation system and resulted in the massive accumulation of ROS in PCs As shown by TEM, Huaier-treated PCs exhibited a decrease in mitochondrial cristae and a smaller mitochondrion, accompanied by an increase in autophagosomes. Indeed, we found that autophagy can induce ferroptosis in PCs and that Huaier-induced ferroptosis can be suppressed by the autophagosome inhibitor, Wortmannin. Conclusion: Huaier can activate ferroptosis by inducing autophagy in PCs.