Development Of Antitumor Drugs Research Articles

Curcumin: Epigenetic Modulation and Tumor Immunity in Antitumor Therapy.

Curcumin is the main ingredient of the Chinese herbal turmeric rhizome, used to treat tumors, diabetes, inflammation, neurodegenerative diseases, cardiovascular diseases, metabolic syndrome, and liver diseases. The antitumor effects of curcumin have received even more attention. One of the main mechanisms of antitumor effects includes inhibition of tumor invasion and migration, induction of tumor cell apoptosis, and inhibition of various cell signaling pathways. It has been found that the antitumor biological activity of curcumin in the body is associated with epigenetic mechanisms. That also implies that curcumin may act as a potential epigenetic modulator to influence the development of tumor diseases. The immune system plays an essential role in the development of tumorigenesis. Tumor immunotherapy is currently one of the most promising research directions in the field of tumor therapy. Curcumin has been found to have significant regulatory effects on tumor immunity and is expected to be a novel adjuvant for tumor immunity. This paper summarizes the antitumor effects of curcumin from four aspects: molecular and epigenetic mechanisms of curcumin against a tumor, mechanisms of curcumin modulation of tumor immunotherapy, reversal of chemotherapy resistance, and novel drug delivery system of curcumin, which provide new directions for the development of new antitumor drugs.

Research Progress on the Anticancer Activity of Plant Polysaccharides.

Tumor is a serious threat to human health, with extremely high morbidity and mortality rates. However, tumor treatment is challenging, and the development of antitumor drugs has always been a significant research focus. Plant polysaccharides are known to possess various biological activities. They have many pharmacological properties such as immunomodulation, antitumor, antiviral, antioxidative, antithrombotic, and antiradiation effects, reduction of blood pressure and blood sugar levels, and protection from liver injury. Among these effects, the antitumor effect of plant polysaccharides has been widely studied. Plant polysaccharides can inhibit tumor proliferation and growth by inhibiting tumor cell invasion and metastasis, inducing cell apoptosis, affecting the cell cycle, and regulating the tumor microenvironment. They also have the characteristics of safety, high efficiency, and low toxicity, which can alleviate, to a certain extent, the adverse reactions caused by traditional tumor treatment methods such as surgery, radiotherapy, and chemotherapy. Therefore, this paper systematically summarizes the direct antitumor effects of plant polysaccharides, their regulatory effects on the tumor microenvironment, and intervening many common high-incidence tumors in other ways. It also provides data support for the administration of plant polysaccharides in modern tumor drug therapy, enabling the identification of new targets and development of new drugs for tumor therapy.

Synthesis, Biological Evaluation, and Mechanistic Insights of Rubrolide Analogues as Antitumor Agents.

Marine natural products and their analogues have as of now been acknowledged as an important source of bioactive molecules for the treatment of cancer. Rubrolides, a unique group of γ-butenolides derived from marine microorganisms, have shown strong cytotoxic activity against various tumor cells. In this study, we synthesized and characterized 21 rubrolide analogues (including 16 new compounds) and investigated their antitumor activities in order to screen more active molecules and elucidate their mechanism of action. Primary MTT assay showed that compounds 1 and 4-9 all exhibited excellent antiproliferative activities. In particular, compound 7 showed broad-spectrum cytotoxic activity against six tumor cell lines, with IC50 values mostly ranging from 2.5 to 0.2 μM. Further mechanistic studies revealed that compound 7 could penetrate HCT116 and Hela cells, localize in the endoplasmic reticulum, and upregulate the PERK-eIF2α-CHOP pathway, inducing ER stress and increasing intracellular reactive oxygen species (ROS) levels to ultimately trigger apoptosis in tumor cells. Additionally, compound 7 was found to upregulate Cyclin B1 protein expression, causing cell cycle reticulum at the G2/M phase. In vivo studies further demonstrated that liposomal delivery of compound 7 exhibited a potent antitumor efficacy against Hela xenograft tumors. Based on these results, marine-derived rubrolide analogues show significant potential as novel lead compounds for antitumor drug development.

Discovery of New Immunomodulatory Anticancer Thalidomide Analogs: Design, Synthesis, Biological Evaluation and In Silico Studies.

New thalidomide analogs have been designed and synthesized by hybridizing the immunomodulatory gutarimide moiety with three antiproliferative nuclei: quinazolinedione, phthalazinedione, and quinoxalinone. The biological results revealed the strong impact of quinazoline derivatives 7a and 28, and phthalazine based 20a against HepG-2, MCF-7, PC3, and HCT-116 cell lines, compared to thalidomide. In particular, compound 20a was the most promising as it had far better biological activity than thalidomide with regard to inhibition of TNF-α, IL-6, caspase 3, COX-I/II, and VEGFR-2, as well as cell cycle arrest, and apoptosis rate enhancement in MCF-7 cells, the most sensitive cell line to the current new molecules. Compound 20a caused reduction in levels of TNF-α and IL-6 by 75.22% and 82.51%, respectively. It elevated the caspase-3 level by 7.21-fold. Furthermore, IC50 against COX-I, COX-II, and VEGFR-2 were 0.65 μM, 0.33 μM, and 232 nM, respectively. In addition, it raised the apoptosis rate from 65.65% to 99.89%. Moreover, 20a was further examined through a docking study and a 200 ns molecular dynamics simulation for its complex with VEGFR-2, along with computational ADME properties. This work suggests the high significance of compounds 20a, 7a and 28, as lead compounds for development of new effective immunomodulatory antitumor drugs.

Design, Synthesis, and Hypoxia-Inducible Factor-1α Inhibitory Activity Evaluation of Panaxadiol Derivatives Containing a Thiazole Moiety.

The hypoxia-inducible factor-1α (HIF-1α) pathway has been implicated in tumor angiogenesis, growth, and metastasis. Therefore, the inhibition of this pathway is an important therapeutic target for cancer. Thiazole derivatives have been reported to have diverse biological activities, especially in terms of anti-tumor. Consequently, we hypothesized that the introduction of a thiazole functional group in PD was likely to improve the biological potency. Here, three series of PD derivatives containing a thiazole moiety were synthesized, including (a) sulfonyl-containing thiazole derivatives (5 a-l), (b) urea-containing thiazole derivatives (7 a-i), and (c) thiourea-containing thiazole derivatives (9 a-i), and evaluated for HIF-1α inhibitory activity using a Hep3B cell-based luciferase reporter assay. The results showed that about 1/3 of the target compounds showed moderate or strong HIF-1α inhibitory activity, among which compounds 5 d and 7 b showed the strongest inhibitory activity with IC50 values of 17.37 and 6.42 μM, respectively, and did not show any significant cytotoxicity. Western blot assay results indicated that these two compounds exhibited more potent inhibition, compared with panaxadiol, of the expression of HIF-1α protein in Hep3B cells at a concentration of 50 μM. Molecular docking experiments were also performed to investigate the structure-activity relationship. Compounds 5 d and 7 b can be used as leads for further study and development of novel antitumor drugs.

Design, synthesis, and in vitro and in vivo biological evaluation of dihydroartemisinin derivatives as potent anti-cancer agents with ferroptosis-inducing and apoptosis-activating properties

Natural products play a pivotal role in drug development, including their direct use as pharmaceuticals and their structural modification, yielding molecules with enhanced therapeutic potential. The discovery of bioactive molecules, lead compounds, and novel drugs is intrinsically linked to the structural optimization of natural products. In this study, forty-one derivatives of dihydroartemisinin (DHA) were synthesized by incorporating fragments with anti-tumour activity via molecular hybridization, and assessed for their anti-proliferative activity against human cancer cell lines (A549, Bel-7402, HCT-116, and SW620) and normal human liver cells (LO2). Most derivatives exhibited superior anti-proliferative activity compared to DHA. Notably, compound A3, featuring a 4-Cl phenyl carbamate moiety, demonstrated significant anti-proliferative activity against HCT-116 cells with an IC50 of 0.31 μM, making it 16-fold more potent than DHA (IC50 = 5.10 μM). The anti-proliferative mechanism did not involve cytotoxicity (SI = 54.13), indicating its superior safety profile compared to DHA (SI = 1.65).Further mechanistic studies revealed that compound A3 inhibits HCT-116 cell proliferation by modulating the expression of PI3K/AKT/mTOR and STAT3 proteins. STAT3 downregulation represses the expression of the critical ferroptosis protein glutathione peroxidase 4 (GPX4), aggravating the accumulation of reactive oxygen species (ROS) and depletion of glutathione (GSH). This redox imbalance triggers and accelerates ferroptosis. Additionally, A3 also induces apoptosis by damaging mitochondria and influencing MAPK signaling. Compound A3 arrested cells in the G2/M phase by regulating p53 expression. In an HCT-116 xenograft mouse model, compound A3 exhibited significant anti-cancer efficacy, with a tumor growth inhibition rate of 58.7 %. Therefore, compound A3 thus has the potential to serve as a lead compound for the development of new anti-tumor drugs.

Design, synthesis and biological evaluation of 4,6-diarylquinoxaline-based KDM4D inhibitors

Histone lysine demethylase 4D (KDM4D) is a critical player in the regulation of tumorigenesis, emerging as a potential target for developing anti-tumor agents. In this study, a series of KDM4D inhibitors containing the 4,6-diarylquinoxaline scaffold were prepared based on the previously discovered hit compound QD-1. Among these inhibitors, 33a was the most potent compound, with an IC50 value of 0.62 μM. In an in vitro assay, 33a showed a superior ability to inhibit the viability of liver cancer Huh-7 cells with IC50 = 5.23 μM. 33a exhibits significant effects in inhibiting cell cycle progression and proliferation of liver cancer cells, as well as suppressing cell migration. This work provided a promising scaffold for developing KDM4D inhibitors, as well as a lead compound for the development of anti-tumor drugs targeting KDM4D.

Flavonoids as modulators of metabolic reprogramming in renal cell carcinoma (Review).

Renal cell carcinoma (RCC) is distinguished by its varied metabolic reprogramming driven by tumor suppressor gene dysregulation and oncogene activation. Tumors can adapt nutrient uptake and metabolism pathways to meet the altered biosynthetic, bioenergetic and redox demands of cancer cells, whereas conventional chemotherapeutics and molecular inhibitors predominantly target individual metabolic pathways without addressing this adaptability. Flavonoids, which are well‑known for their antioxidant and anti‑inflammatory properties, offer a unique approach by influencing multiple metabolic targets. The present comprehensive review reveals the intricate processes of RCC metabolic reprogramming, encompassing glycolysis, mitochondrial oxidative phosphorylation and fatty acid biosynthesis. The insights derived from the present review may contribute to the understanding of the specific anticancer mechanisms of flavonoids, potentially paving the way for the development of natural antitumor drugs focused on the metabolic reprogramming of RCC.

Synthesis, pharmacological evaluation, and modeling of novel quaternary ammonium salts derived from β-carboline containing an imidazole moiety as angiogenesis inhibitors

In this study, a series of novel β-carboline condensed imidazolium derivatives (7a-7y) were designed and synthesized by incorporating imidazolium salt structures into β-carboline. The cytotoxicity of compounds 7a-7y was evaluated in various cancer cell lines, including lung cancer (A549), gastric cancer (BGC-823), mouse colon cancer (CT-26), liver cancer (Bel-7402), and breast cancer (MCF-7), using the MTT assay. Most compounds exhibited significant activity against one or more of the cancer cell lines. Notably, compounds 7 g, 7o, 7r, 7 s, 7u, 7v, 7x, and 7w showed the highest cytotoxic activity (IC50 < 2 μM) in the tested tumor cell lines. Compound 7x demonstrated cytotoxic activities of 1.3 ± 0.3 μM (for BGC-823), 2.4 ± 0.4 μM (against A549), 7.8 ± 0.9 μM (for Bel-7402), and 9.8 ± 1.4 μM (against CT-26). The chick chorioallantoic membrane assay revealed significant anti-angiogenic potential of compound 7x. Molecular imprinting studies suggested the anti-angiogenic effect of compound 7x might be attributed to inhibition of VEGFR2 kinase. Molecular docking and molecular dynamics further indicate that its activity may be primarily associated with the potential inhibition of VEGFR2. Our research outcomes have provided valuable lead compounds for the development of novel antitumor drugs and have offered beneficial insights for subsequent drug design and optimization.

Application of Pharmacometrics in Advancing the Clinical Research of Antibody-Drug Conjugates: Principles and Modeling Strategies.

Antibody-drug conjugates (ADCs) have become a pivotal area in the research and development of antitumor drugs. They provide innovative possibilities for tumor therapy by integrating the tumor-targeting capabilities of monoclonal antibodies with the cytotoxic effect of small molecule drugs. Pharmacometrics, an important discipline, facilitates comprehensive understanding of the pharmacokinetic characteristics of ADCs by integrating clinical trial data through modeling and simulation. However, due to the complex structure of ADCs, their modeling approaches are still unclear. In this review, we analyzed published population pharmacokinetic models for ADCs and classified them into single-analyte, two-analyte, and three-analyte models. We also described the benefits, limitations, and recommendations for each model. Furthermore, we suggested that the development of population pharmacokinetic models for ADCs should be rigorously considered and established based on four key aspects: (1) research objectives; (2) available in vitro and animal data; (3) accessible clinical information; and (4) the capability of bioanalytical methods. This review offered insights to guide the application of pharmacometrics in the clinical research of ADCs, thereby contributing to more effective therapeutic development.

Targeting SERCA2 in Anti-Tumor Drug Discovery.

SERCA2, a P-type ATPase located on the endoplasmic reticulum of cells, plays an important role in maintaining calcium balance within cells by transporting calcium from the cytoplasm to the endoplasmic reticulum against its concentration gradient. A multitude of studies have demonstrated that the expression of SERCA2 is abnormal in a wide variety of tumor cells. Consequently, research exploring compounds that target SERCA2 may offer a promising avenue for the development of novel anti-tumor drugs. This review has summarized the anti-tumor compounds targeting SERCA2, including thapsigargin, dihydroartemisinin, curcumin, galangin, etc. These compounds interact with SERCA2 on the endoplasmic reticulum membrane, disrupting intracellular calcium ion homeostasis, leading to tumor cell apoptosis, autophagy and cell cycle arrest, ultimately producing anti-tumor effects. Additionally, several potential research directions for compounds targeting SERCA2 as clinical anti-cancer drugs have been proposed in the review. In summary, SERCA2 is a promising anti-tumor target for drug discovery and development.

Identification of lysine lactylation (kla)-related lncRNA signatures using XGBoost to predict prognosis and immune microenvironment in breast cancer patients

Breast cancer (BC) stands as a predominant global malignancy, significantly contributing to female mortality. Recently uncovered, histone lysine lactylation (kla) has assumed a crucial role in cancer progression. However, the correlation with lncRNAs remains ambiguous. Scrutinizing lncRNAs associated with Kla not only improves clinical breast cancer management but also establishes a groundwork for antitumor drug development. We procured breast tissue samples, encompassing both normal and cancerous specimens, from The Cancer Genome Atlas (TCGA) database. Utilizing Cox regression and XGBoost methods, we developed a prognostic model using identified kla-related lncRNAs. The model's predictive efficacy underwent validation across training, testing, and the overall cohort. Functional analysis concerning kla-related lncRNAs ensued. We identified and screened 8 kla-related lncRNAs to formulate the risk model. Pathway analysis disclosed the connection between immune-related pathways and the risk model of kla-related lncRNAs. Significantly, the risk scores exhibited a correlation with both immune cell infiltration and immune function, indicating a clear association. Noteworthy is the observation that patients with elevated risk scores demonstrated an increased tumor mutation burden (TMB) and decreased tumor immune dysfunction and exclusion (TIDE) scores, suggesting heightened responses to immune checkpoint blockade. Our study uncovers a potential link between Kla-related lncRNAs and BC, providing innovative therapeutic guidelines for BC management.

Curcumin/nido-carborane complexes incorporated with crown ether/sodium alginate encapsulated drug delivery strategies exhibit pH-responsive release and enhanced in vitro anti-tumor activity

Curcumin has excellent anti-tumor activity, but its instability at physiological pH, low bioavailability and poor targeting limit curcumin to further become an excellent anticancer drug. In this study, two curcumin/nido-carborane fluorescent polymers, curcumin-borane-crown ether coated by sodium alginate (SA-CBC) and curcumin-borane-crown ether (CBC), were prepared, and SA-CBC with better properties to be the most promising anti-tumor drugs. Crown ether/sodium alginate drug delivery strategies can improve the release property of curcumin. Nido-carborane enhances the targeting of curcumin and the inhibiting effect on tumor cells. After testing, the fluorescence lifetime of SA-CBC was 4.72 ns, indicating good fluorescence properties. In vitro drug release results showed that the constructed drug delivery system released curcumin at a controlled rate. The results of transmission electron microscopy and particle size showed that SA-CBC was well encapsulated, with a particle size of less than 200 nm, easy to be absorbed in vivo. Bioactivity studies showed that SA-CBC had a strong affinity and inhibiting effect on tumor cells, and the inhibition rate could reach 84.5 %. In conclusion, this study provides an innovative protocol for the design of curcumin anticancer drugs and lays the foundation for the development of more effective anti-tumor drugs with small side effects.

Chemical Constituents, Anti-Tumor Mechanisms, and Clinical Application: A Comprehensive Review on Scutellaria barbata.

With the increasing global incidence and mortality rates of cancer, the development of novel anti-tumor drugs has become particularly urgent. Scutellaria barbata D. Don, a perennial herb belonging to the genus Scutellaria in the family Lamiaceae, has aroused extensive attention for its medicinal value in recent years. This article presents an exhaustive review of the flavonoid, diterpene, and other chemical constituents harbored within Scutellaria barbata, delving into the intricate mechanisms by which these compounds orchestrate their anti-tumor effects via diverse biological pathways. Remarkably, these compounds distinguish themselves through their capability to regulate cellular signaling, inhibit cancer cell proliferation, trigger apoptosis, disrupt angiogenesis, and bolster immune responses. These anti-tumor effects are achieved through strategic modulation of pivotal signaling cascades, particularly the PI3K/Akt/mTOR, MAPK, and NFκB pathways. In addition, this article also summarizes the clinical applications of Scutellaria barbata in tumor treatment, especially its potential in alleviating the side effects of radiotherapy and chemotherapy and improving patients' quality of life. In conclusion, this review comprehensively summarizes and analyzes the chemical constituents, anti-tumor mechanisms, and clinical applications of Scutellaria barbata, with the aim of systematically reviewing the existing research results and exploring potential future research directions.

Multicellular 3D bioprinted human gallbladder carcinoma for in vitro mimicry of tumor microenvironment and intratumoral heterogeneity

Gallbladder carcinoma (GBC) is a malignant hepatobiliary cancer characterized by an intricate tumor microenvironments (TME) and heterogeneity. The traditional GBC 2D culture models cannot faithfully recapitulate the characteristics of the TME. Three-dimensional (3D) bioprinting enables the establishment of high-throughput and high-fidelity multicellular GBC models. In this study, we designed a concentric cylindrical tetra-culture model to reconstitute the spatial distribution of cells in tumor tissue, with the inner portion containing GBC cells, and the outer ring containing a mixture of endothelial cells, fibroblasts, and macrophages. We confirmed the survival, proliferation, biomarker expression and gene expression profiles of GBC 3D tetra-culture models. Hematoxylin-eosin (HE) and immunofluorescence staining verified the morphology and robust expression of GBC/endothelial/fibroblast/macrophage biomarkers in GBC 3D tetra-culture models. Single-cell RNA sequencing revealed two distinct subtypes of GBC cells within the model, glandular epithelial and squamous epithelial cells, suggesting the mimicry of intratumoral heterogeneity. Comparative transcriptome profile analysis among variousin vitromodels revealed that cellular interactions and the TME in 3D tetra-culture models reshaped the biological processes of tumor cells to a more aggressive phenotype. GBC 3D tetra-culture models restored the characteristics of the TME as well as intratumoral heterogeneity. Therefore, this model is expected to have future applications in tumor biology research and antitumor drug development.

Design, synthesis and antitumor activity of 3,4,5-Trisubstituted Isoxazoles

In this study, 56 isoxazole derivatives were synthesized and their antitumor activity against 9 cancer cells, such as BXPC-3, MiaPaCa-2, PANC-1, MCF-7, HCT-116, HepG2, NCI-H460, A549 and B16 was detected. The results of pharmacological experiments indicated that most compounds exhibit good cytotoxicity against nine cancer cells. Among them, compound 14–3 has an IC50 of 2.4 μM for colon cancer cells HCT-116, which shows the best effect and is better than the broad-spectrum drug 5-Fluorouracil (5-Fu) for the treatment of colon cancer. In addition, 14–3 induces apoptosis and leads to cell cycle arrest in the G2/M phase. Cytotoxicity tests on human normal hepatocytes LO2 also demonstrates that 14–3 is less toxic than 5-Fu with no obvious toxicity. These results suggest that 14–3 is a potential candidate for the development of anti-tumor drugs.

Discovery of Preclinical Candidate AD1058 as a Highly Potent, Selective, and Brain-Penetrant ATR Inhibitor for the Treatment of Advanced Malignancies.

The ataxia telangiectasia-mutated and Rad3-related protein (ATR) plays a crucial role in regulating the cellular DNA-damage response (DDR), making it a promising target for antitumor drug development through synthetic lethality. In this study, we present the discovery and detailed characterization of AD1058, a highly potent and selective ATR inhibitor, with good preclinical pharmacokinetic profiles. AD1058 exhibits superior efficacy in inhibiting cell proliferation, disrupting the cell cycle, and inducing apoptosis compared to AZD6738. AD1058 displays potent antitumor effects as a single agent or in combination with clinically approved tumor therapies such as PARP inhibitors, ionizing radiotherapy, or chemotherapy in vivo. Considering its enhanced ability to permeate the blood-brain barrier, AD1058 is a promising clinical candidate for the treatment of brain metastases and leptomeningeal metastases in solid tumors. Additionally, among reported ATR inhibitors, AD1058 features the shortest synthesis route and the highest efficiency to date.

Curcumol promotes ferroptosis of colon cancer by targeting the ubiquitination and degradation of GPX4

Background and aimColon cancer (CC) is one of the common malignant tumors in the digestive tract, the prognosis of CC patients has never been satisfying. A Ferrous-dependent form that regulates cell death, plays a key role in cancer development. As a core regulator of ferroptosis, GPX4 has become a potential molecular target for the development of antitumor drugs. Curcumol (Cur), a sesquiterpene natural product, it has significant anti-tumor effect. However, whether Cur mediates ferroptosis in colon cancer and its mechanism are still unclear. This study aimed to investigate the underlying mechanisms of Cur anti-tumor. Experimental procedureBy investigating the Cancer Genome Atlas (TCGA) database and tissue immunofluorescence staining was also used to detect the levels of GPX4 protein in CC and matching paracancerous tissues. The anti-CC and pro-ferroptosis effects of Cur were detected in the vivo and vitro experiment. The interaction between Cur and GPX4 was predicted. In addition, the potential mechanism of Cur anti-CC was further discussed. Co-immunoprecipitation was used to confirm Cur-mediated GPX4 ubiquitination. Results and conclusionGPX4 was upregulated in CC tissue and was correlated with poor survival of patients. Cur inhibited the proliferation of CC cells, accompanied by regulating Fe2+ overload, reactive oxygen species (ROS) formation, malondialdehyde (MDA) production and superoxide dismutase (SOD) consumption. Furthermore, GPX4 was predicted and verified as the direct target of Cur by molecular docking and structure-based virtual prediction. Meanwhile, Cur could promote the ubiquitination-mediated degradation of GPX4, induce ferroptosis in CC cells and regulate the expression of ferroptosis-related protein FTH1 and TfR1. In addition, when GPX4 was overexpressed (GPX4-OE), the inhibitory effect of Cur on the expression of GPX4 and ferroptosis-related protein FTH1 and the promotion of TfR1 expression were abolished. Cur could inhibit CC by increasing the ubiquitination degradation level of GPX4 to induce ferroptosis in CC cells.

Kuwanon C Inhibits Tumor Cell Proliferation and Induces Apoptosis by Targeting Mitochondria and Endoplasmic Reticulum.

Kuwanon C is a unique flavonoid found in the mulberry family, characterized by two isopentenyl groups. While previous research has focused on various properties of kuwanon C, such as antioxidant, hypoglycemic, antimicrobial, food preservation, skin whitening, and nematode lifespan extension, little attention has been given to its potential role in oncological diseases. In this study, we investigate the antitumor effect of kuwanon C in cervical cancer cells and elucidate its specific mechanism of action. We assessed the antitumor effects of kuwanon C using various experimental techniques, including cell proliferation assay, wound healing assays, EdU 488 proliferation assay, mitochondrial membrane potential assay, ROS level assay, cell cycle, apoptosis analysis, and studies on kuwanon C target sites and molecular docking. The results revealed that kuwanon C significantly impacted the cell cycle progression of HeLa cells, disrupted their mitochondrial membrane potential, and induced a substantial increase in intracellular ROS levels. Moreover, kuwanon C exhibited notable anti-proliferative and pro-apoptotic effects on HeLa cells, surpassing the performance of commonly used antitumor drugs such as paclitaxel and cisplatin. Notably, kuwanon C demonstrated superior efficacy while also being more easily accessible compared to paclitaxel. Our study demonstrates that kuwanon C exerts potent antitumor effects by its interaction with the mitochondrial and endoplasmic reticulum membranes, induces a significant production of ROS, disrupts their normal structure, inhibits cell cycle progression, and stimulates apoptotic signaling pathways, ultimately resulting in the death of HeLa tumor cells. As an isopentenyl compound derived from Morus alba, kuwanon C holds great promise as a potential candidate for the development of effective antitumor drugs.

ROS induced pyroptosis in inflammatory disease and cancer.

Pyroptosis, a form of caspase-1-dependent cell death, also known as inflammation-dependent death, plays a crucial role in diseases such as stroke, heart disease, or tumors. Since its elucidation, pyroptosis has attracted widespread attention from various sectors. Reactive oxygen species (ROS) can regulate numerous cellular signaling pathways. Through further research on ROS and pyroptosis, the level of ROS has been revealed to be pivotal for the occurrence of pyroptosis, establishing a close relationship between the two. This review primarily focuses on the molecular mechanisms of ROS and pyroptosis in tumors and inflammatory diseases, exploring key proteins that may serve as drug targets linking ROS and pyroptosis and emerging fields targeting pyroptosis. Additionally, the potential future development of compounds and proteins that influence ROS-regulated cell pyroptosis is anticipated, aiming to provide insights for the development of anti-tumor and anti-inflammatory drugs.