Types Of Cancer Cells Research Articles

Poly(Epsilon-Lysine) Dendrons Inhibit Proliferation in HER2-Overexpressing SKBR3 Breast Cancer Cells at Levels Higher than the Low-Expressing MDA-MB-231 Phenotype and Independently from the Presentation of HER2 Bioligands in Their Structure

Among the known breast cancers, the subtype with HER2 receptors-overexpressing cells is associated with a poor prognosis. The adopted monoclonal antibody Trastuzumab has improved clinical outcomes, but it is associated with drug resistance and relatively high costs. The present work adopted the peptide solid-phase synthesis method to synthesise branched poly(ε-lysine) peptide dendrons with 8 branching arms integrating, at their carboxy terminal molecular root, either an arginine or the HER2 receptor-binding sequence LSYCCK or the scramble sequence CSCLYK. These dendrons were synthesised in quantities higher than 100 mg/batch and with a purity exceeding 95%. When tested with two types of breast cancer cells, the dendrons led to levels of inhibition in the HER2 receptor-overexpressing breast cancer cells (SKBR3) comparable to Trastuzumab and higher than breast cancer cells with low receptor expression (MDA-MB-231) where inhibition was more moderate. Noticeably, the presence of the amino acid sequence LSYCCK at the dendron molecular root did not appear to produce any additional inhibitory effect. This was demonstrated also when the scramble sequence CSCLYK was integrated into the dendron and by the lack of any antiproliferative effect by the control linear target sequence. The specific inhibitory effect on proliferation was finally proven by the absence of cytotoxicity and normal expression of the cell migration marker N-Cadherin. Therefore, the present study shows the potential of poly(ε-lysine) dendrons as a cost-effective alternative to Trastuzumab in the treatment of HER2-positive breast cancer.

Glutathione transferase omega 1-1 (GSTO1-1) can effect the inter-cell transfer of cisplatin resistance through the exosomal route.

Glutathione transferase omega-1-1 (GSTO1-1) is a member of the glutathione transferase superfamily (GSTs) involved in the modulation of cell survival, proliferation and metabolism. Increased levels of GSTO1-1 have been associated with cancer progression and chemoresistance in different types of cancer cells, possibly supported by the post-traslational regulation of some major prosurvival pathways regulated by the enzyme. Our data demonstrate for the first time that GSTO1-1 can be released by cancer cells through the exosomal route and transferred to GSTO1-1 knock-out cells, this resulting in an increased resistance against cisplatin toxicity in recipient cells. The use of the exosomal route to transfer the regulatory competences of GSTO1-1 could be a further element supporting its role in neoplastic progression.

Terahertz cancer cell sensor based on plasmonic toroidal metasurface

This paper investigates a plasmonic toroidal metasurface cancer cell sensor capable of highly sensitive, cost-effective, and label-free detection. Utilizing titanium and gold split ring resonators, the metasurface unit are formed. Numerical findings indicate a significant resonance frequency shift of the metasurface upon changes in the measured substance, enabling accurate detection of various cancer cell types, such as blood cancer cell and cervical cancer cell in the 2.5 THz-4.5 THz band, with sensitivity reaching 1.075 THz/RIU. Moreover, the metasurface sensor demonstrates superior angular stability and high sensitivity in detecting cyanide and heavy metal-contaminated water. These research outcomes lay a theoretical foundation for the development and application of highly sensitive cancer cell sensors.

Metformin induces apoptosis in TRAIL-resistant colorectal cancer cells

Resistance to chemotherapy drugs, which commonly occurs during the treatment of colorectal cancer (CRC), can lead to tumor recurrence and metastasis, so combinational treatment strategies according to the cancer cell type are urgently needed to overcome drug resistance and increase therapeutic efficiency. To this end, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising anticancer strategy. Some CRC cell lines such as SW620 have low sensitivity to TRAIL, so additional sensitizers are required to make the strategy effective. Therefore, we focused on the apoptotic effect of combinational metformin and TRAIL treatment on TRAIL-resistant SW620 cells. Treatment with TRAIL alone did not induce apoptosis whereas combined treatment with metformin and TRAIL significantly increased it. TRAIL activated caspases through an extrinsic pathway but increased resistance to apoptosis through the protein kinase B or AKT (PKB/AKT)/mammalian target of rapamycin (mTOR) pathway. On the other hand, metformin reduced the inhibitory effect of X-linked inhibitor of apoptosis (XIAP) by blocking the AKT and nuclear factor kappa B (NF-κB) pathways and activated CCAAT-enhancer-binding protein homologous protein (CHOP) via endoplasmic reticulum (ER)-stress but without inducing apoptosis. In addition, metformin induced cell-cycle arrest, thereby blocking cell proliferation and growth. These results were also confirmed through an in vivo mouse xenograft CRC model, in which combined treatment with metformin and TRAIL induced tumor cell death, thus demonstrating the anticancer effect of their coadministration. Therefore, cotreatment of metformin and TRAIL could be an effective anticancer treatment strategy for TRAIL-resistant CRC.

Integrated single-cell transcriptomic analyses identify a novel lineage plasticity-related cancer cell type involved in prostate cancer progression

Cancer cell plasticity is the ability of neoplastic cells to alter their identity and acquire new biological properties under microenvironmental pressures. In prostate cancer (PCa), lineage plasticity often results in therapy resistance and trans-differentiation to neuroendocrine (NE) lineage. However, identifying the cancer cells harboring lineage plasticity-related status remains challenging. Based on 13 multi-center human PCa bulk transcriptomic cohorts (samples=3314) and 9 bulk transcriptomic datasets derived from PCa experimental models, we established an integrated lineage plasticity-related gene signature, termed LPSig. Leveraging this gene signature, AUCell enrichment analysis was applied to identify the cell population with high lineage plasticity from a comprehensive single-cell RNA-sequencing (scRNA-seq) meta-atlas assembled by us, which consisted of 10 public human PCa scRNA-seq datasets (samples=93, cells=222,529). Moreover, additional scRNA-seq dataset of human PCa, multiplex immunohistochemistry staining for human PCa tissues, invitro and invivo functional experiments, as well as qPCR and Western blot analyses were employed to validate our findings. We found that LPSig could finely capture the dynamics of tumor lineage plasticity throughout the progression of PCa, accurately estimating the status of lineage plasticity. Based on LPSig, we identified a previously undefined minority population of lineage plasticity-related PCa cells (LPCs) from the human PCa scRNA-seq meta-atlas assembled by this study. Furthermore, in-depth dissection revealed pivotal roles of LPCs in trans-differentiation, tumor recurrence, and poor patient survival during PCa progression. Furthermore, we identified HMMR as a representative cell surface marker for LPCs, which was validated using additional scRNA-seq datasets and multiplexed immunohistochemistry. Moreover, HMMR was transcriptionally inhibited by androgen receptor (AR), and was required for the aggressive adenocarcinoma features and NE phenotype. Our study uncovers a novel population of lineage plasticity-related cells with low AR activity, stemness-like traits, and elevated HMMR expression, that may facilitate poor prognosis in PCa. This work was supported by National Key R&D Program of China (2022YFA0807000), National Natural Science Foundation of China (82160584), Advanced Prostate Cancer Diagnosis and Treatment Technology Innovation Team of Kunming Medical University (CXTD202216), and Reserve Talents of Young and Middle-aged Academic Leaders in Yunnan Province (202105AC160013).

A Review of Anticancer Potential of Conferone, Diversin and Ferutinin; Which One is Stronger for Cancer Therapy?

One of the growing diseases in today's human societies is cancer, which has become a major challenge, especially in industrialized and developing countries. Cancer treatments are diverse, but they usually use surgery, chemotherapy, and radiotherapy to improve patients. Existing drugs are usually expensive and, in some cases, are not effective due to drug resistance and side effects. Finding compounds of natural origin can be somewhat effective and useful in helping doctors to treat this disease. Ferula plants, which are traditionally used as spices or for medicinal purposes, can be a good source for finding anti-cancer compounds due to their various compounds, such as monoterpenes, sulfide compounds, and polyphenols. Several studies have shown that compounds found in Ferula plants have significant anticancer effects on various types of cancer cells. This article was compiled with the aim of collecting evidence and articles related to the anti-cancer effects of three compounds obtained from these plants, namely Conferone, Diversin, and Ferutinin. This review article was prepared by searching the terms Conferone, Diversin, Ferutinin and cancer and related information was collected through searching electronic databases such as ISI Web of Knowledge, PubMed and Google Scholar until the March of 2024. The results of this review showed that relatively comprehensive studies have been conducted in this field and these studies have shown that these compounds can be used in the design of future anticancer drugs. Among the examined compounds, conferone showed that it has the best effect on cancer cells.

Estro-Androgenic Disrupting Effects of Halogenated Disinfection Byproducts: A Comprehensive Evaluation and Comparison.

Drinking water halogenated disinfection byproducts (DBPs) have become an increasing health concern. However, the endocrine-disrupting effects of DBPs have not been well evaluated, and the limited available data have inhibited a comprehensive understanding of their health risks. In this study, a total of 43 DBPs were evaluated for their estro-androgenic effects using two types of human breast cancer cells. Among the tested DBPs, 16 exhibited estrogenic/antiestrogenic/androgenic/antiandrogenic effects, and the effects could be observed even at concentrations typically detected in drinking water. Iodinated and polyhalogenated DBPs generally showed higher effects than other species. For a broader comparison, DBP endocrine-disrupting effect data from this study and previous studies were summarized. It was found that the endocrine disruption efficacy of DBPs followed the rank order of iodinated > brominated > chlorinated species, and halophenolic DBPs were potential endocrine-disrupting compounds. Moreover, molecular docking results demonstrated that the binding of DBPs to estro-androgenic receptors was dominated by hydrophobic bonding, hydrogen bonding, halogen bonding, and van der Waals forces. The force strength and molecular volume were related to the magnitude of the estro-androgenic effects. Iodinated DBPs and polyhalogenated DBPs tended to have larger binding forces than other analogues and thus exhibited stronger effects.

Angiotensin II as a linking factor in cardiovascular disease enhanced cancer growth

Abstract Introduction Several publications have demonstrated that cardiovascular diseases (CVD) promote tumor growth in mouse models of breast, lung, and colon cancer, suggesting a causal relationship between both diseases. Cancer and CVD share several risk factors and pathophysiological mechanisms, including inflammation, oxidative stress, neurohormonal activation, and immune system dysfunction that combined could explain why patients with CVD are prone to develop cancer. Recent reports also suggest a link between hypertension and lung cancer, and between cardiac hypertrophy and breast cancer. Angiotensin II (ANGII) is a hormone involved in blood pressure regulation, vascular hemostasis and hypertrophy development. Moreover, ANGII is cancerogenic by increasing proliferation of several cancer cell types. Hence, ANGII could be a link in CVD-induced enhancement of cancer growth. Here, we investigated whether ANGII treatment, and subsequent hypertension and cardiac hypertrophy, could promote cancer growth and metastasis. Methods ANGII (2000ng.kg-1.min-1, 4w) was administered to 10w old C57B6/J mice using subcutaneous osmotic minipumps. After 3w, 5*10^5 Lewis lung carcinoma (LLC) cells or 2*10^5 MC38 colon cancer cells were injected onto the right flank of the mice. Tumor growth was monitored over 21d using a digital caliper. Tumor volume was calculated using the following formula: Length × width² × 0.5 On day 22, mice were sacrificed for further post-mortem analysis. Cardiac echography was performed after 3w of ANGII treatment and before sacrifice to assess cardiac function (data not shown). To assess the formation of cardiac fibrosis trichrome staining’s were performed. In addition, the effect of ANGII on LLC metastasis was investigated. Mice were treated with ANGII as described above. LLC cells, 2*10^6, were injected intravenously (i.v.). Mice were sacrificed 21d after cell injection. Metastatic growth was visualized and quantified by organ weighing and H&E staining. Results LLC tumor growth was significantly increased by ANGII treatment. In addition, post-mortem tumor weight was increased (0.62 ± 0.05 g control vs. 1.17 ± 0.24 g ANGII). Furthermore, we found lung weight increased in the ANGII-treated group injected i.v. with LLC cells, indicating an increase in metastatic growth (0.41 ± 0.08 g control vs. 0.57 ± 0.04 g ANGII). Interestingly, MC38 tumor growth decreased in the ANGII treated group as portrayed by the tumor weight (0.42 ± 0.06 g control vs. 0.19 ± 0.05 g ANGII). Figure 1 shows the tumor growth over time and tumor volume, weight post-mortem. Conclusion Our data suggest a role for ANGII in CVD-enhanced cancer growth, but also that this effect is not universal, illustrated by a differential effect of ANGII on distinct cancer types. Although further investigation is required to unravel the role of ANGII, screening cancer patients with CVD comorbidities for ANGII involvement might be warranted.

Serum from Hypertensive Patients Induces Cancer-Supporting Phenotype of Vascular Endothelium In Vitro

Background/Objectives: Large-scale epidemiological studies have established a bidirectional association between hypertension and cancer. However, the underlying mechanisms explaining this connection remain unclear. In our study, we investigated whether serum from patients with hypertension (HT) could enhance the aggressiveness of cancer cells in vitro through alterations in endothelial cell phenotype. Methods: Experiments were performed using EAhy926 endothelial cells and ovarian (SKOV-3), colorectal (SW480), pancreatic (PSN-1), breast (MCF-7), and lung (A549) cancer cell lines. Results: This study showed that conditioned medium (CM) produced by EAhy926 cells, when exposed to serum from patients with untreated hypertension (HT-CM), promotes the proliferation, migration, and invasion of every cancer cell line tested. In addition, endothelial cells subjected to HT serum promote the adhesion of all cancer cell types except PSN-1. An intensified transendothelial invasion of cancer cells was accompanied by decreased expression of junctional proteins (connexin 43, E-cadherin, occluding, desmoglein) in HT serum-treated endothelial cells. Quantitative analysis of the secretome of endothelial cells subjected to HT serum showed that they secrete increased amounts of CCL2, CXCL1, CXCL8, bFGF, HGF, IL-6, PAI-1, and TGF-β1. Moreover, cancer cells exposed to HT-CM display increased mRNA expression for several pro-cancerogenic agents, including CXCL8, tPA, and VEGF. Conclusions: Our report shows that hypertension may potentiate cancer cell aggressiveness by modulating endothelial cell phenotype. Further tests with antihypertensive drugs are required to assess whether effective treatment of hypertension can mitigate its cancer-promoting potential.

Anti-cancer Activity Evaluation of Naphthalenonic and Chromanonic Spiroisoxazoline Derivatives as Selective COX-2 Inhibitors on HT29 Cell Lines

Background: Cyclooxygenase-2 (COX-2) is induced in response to proinflammatory conditions, and it is not only a key enzyme in the inflammatory process, but also seems to be highly expressed in various types of cancer cells. On the other hand, it is well documented that chemical compounds with spiro scaffolds in their structure could be effective chemical agents against cancer types. Objective: In this study, the cytotoxicity effects of spiroisoxazoline derivatives containing naphthalinone and chromanone spiro-bridge were investigated. Methods: The cytotoxicity effects of compounds 7a-7h were evaluated by performing the MTT assay on the HT-29 (colorectal cancer), MCF-7 (breast cancer), and HEK-293 (normal kidney) cell lines. After that, a compound with high yield and remarkable cytotoxic activity was selected to analyze the cell cycle and apoptosis mechanism. Results: The most effective cytotoxic activity was observed on HT-29 and MCF-7 cell lines of compounds 7b (IC50 value: 1.07±0.28 µM) and 7f (IC50 value: 11.92±1.07 µM). None of the compounds had a toxic effect on normal HEK-293 cells, except for compound 7g with an IC50 value of 21.30±16.14 µM, whose effect was much lower than that of cisplatin and doxorubicin, known as anti-cancer agents. Subsequently, compound 7e with significant yield and cytotoxic activity was investigated to evaluate cell cycle and apoptosis. The result showed that compound 7e induced significant G0/G1 cell cycle arrest and apoptosis in HT-29 cells Conclusion: The selective COX-2 inhibitor compounds with spiroisoxazoline core structure could be suitable scaffolds for cytotoxic effects.

Curcumin as a novel therapeutic candidate for cancer: can this natural compound revolutionize cancer treatment?

Cancer remains one of the leading causes of death worldwide. Despite advances in medical treatments, current therapeutic strategies, including radiotherapy, chemotherapy, targeted therapy, and surgical resection, have not significantly reduced the global incidence and mortality rates of cancer. Oncologists face considerable challenges in devising effective treatment plans due to the adverse side effects associated with standard therapies. Therefore, there is an urgent need for more effective and well-tolerated cancer treatments. Curcumin, a naturally occurring compound, has garnered significant attention for its diverse biological properties. Both preclinical studies and clinical trials have highlighted curcumin's potential in cancer treatment, demonstrating its ability to inhibit the proliferation of various cancer cell types through multiple cellular and molecular pathways. This paper examines the antineoplastic properties, and the therapeutic mechanisms including cell signalling pathways targeted by curcumin that are implicated in cancer development and explores the challenges in advancing curcumin as a viable anticancer therapy.

Novel Strategies for Synthesis and Assessment of Dextran Conjugated 9Z,11E Linoleic Acid on Cancer Cell Lines Viability via Wnt/Beta‐Catenin Signaling Pathway and Apoptosis

AbstractConjugated linoleic acid (CLA) is one of the positional and structural isomers of linoleic acid. Ninety percent of the CLA contained in natural foods is the cis‐9(9Z), trans‐11(11E) isomer. CLA also has anti‐carcinogenic, anti‐adipogenic, and anti‐inflammatory properties. Limited studies aim to elucidate the impact of 9Z,11E‐CLA on Wnt/beta‐catenin signaling.In this study, we have selected MDA‐MB‐231, T98G, and SAOS‐2 cell lines of various cancer origins and investigate the impact of dextran conjugated 9Z,11E CLA (Dex‐9Z,11E‐CLA) using cell proliferation assay and immunocytochemical methods. Cytotoxic effects of Dex conjugated 9Z,11E CLA are assessed with the MTT method. It analyzed Wnt/beta‐catenin signaling changes using target molecule beta‐catenin, Dickkopf‐1 (Dkk‐1) as a negative regulator, and active caspase3 (CC3) as an apoptotic marker.Dex‐9Z,11E‐CLA is shown to suppress cell viability in three different types of cancer cells, and the most effective concentration is 200 µm. 9Z,11E‐CLA and Dex‐9Z,11E‐CLA affect the Wnt/beta‐catenin signaling pathway negatively in all cell lines. Beta‐catenin expression is decreased, Dkk‐1 expression is increased, and CC3 positivity is increased significantly compared to the control group. In conclusion, the data suggest that Dex‐9Z,11E‐CLA suppresses cell viability and causes apoptosis in cells via the Wnt/beta‐catenin signaling pathway. Lastly, Dex‐9Z,11E‐CLA harbors novel anticancer potential and exhibits uncontrolled activation of Wnt/beta‐catenin signaling.

Patient-Derived Organoids: A Game-Changer in Personalized Cancer Medicine.

Research on cancer therapies has benefited from predictive tools capable of simulating treatment response and other disease characteristics in a personalized manner, in particular three-dimensional cell culture models. Such models include tumor-derived spheroids, multicellular spheroids including organotypic multicellular spheroids, and tumor-derived organoids. Additionally, organoids can be grown from various cancer cell types, such as pluripotent stem cells and induced pluripotent stem cells, progenitor cells, and adult stem cells. Although patient-derived xenografts and genetically engineered mouse models replicate human disease in vivo, organoids are less expensive, less labor intensive, and less time-consuming, all-important aspects in high-throughput settings. Like in vivo models, organoids mimic the three-dimensional structure, cellular heterogeneity, and functions of primary tissues, with the advantage of representing the normal oxygen conditions of patient organs. In this review, we summarize the use of organoids in disease modeling, drug discovery, toxicity testing, and precision oncology. We also summarize the current clinical trials using organoids.

Exploring the Antitumor Potential of New Indazole-indolizines Designed by Molecular Hybridization

Background: Cancer represents the major health problem faced by the population of the world, remaining one of the main causes of death. Hence, the development of new targeted antitumor drugs with high efficacy and lower toxicity is still needed. Objective: As a continuation of our work to discover new molecules with cytotoxic properties, two heterocyclic scaffolds, namely indolizine, and indazole, were combined in the same molecule, aiming to improve the bioactivity. This article focused on the synthesis, characterization, and biological evaluation of a series of new indazole-indolizine hybrid compounds. Methods: The biological potential of the synthesized compound was investigated in vitro against the human farnesyltransferase enzyme and NCI 60 tumor cell lines panel. While the farnesyltransferase inhibitory activity was modest, a very good antiproliferative action was observed for compound 4a, which, at a concentration of 10 μM, inhibited the growth of 20 types of cancer cells by more than 50% and showed cytotoxic action against the ovarian cancer cell line OVCAR-4. Results: A series of novel indazole-indolizine hybrids were synthesized via a [3+2] cycloaddition reaction, fully characterized and biologically evaluated for antitumor potential. Conclusion: Compound 4a could be a promising starting point in the development of new antitumoral agents. Further biological investigations will be performed to identify the biological target of the compounds. Moreover, different synthetic strategies to introduce new substituents on the indolizine core will be addressed.

Synthesis, Identification, and anti-cancer Evaluation of Some heterocyclic Chitosan-Thiosemicarbazones compounds and their nickle (II) complexes

Chitosan (CS) a chemical substance taken from the shells of sea creatures that has various uses in industry, farming, and medicine, for example in medical dressings. Its derivatives significantly inhibit two types of cancer cells: Madin Darby Canine Kidney MDCK and MCF-7. These derivatives include thiosemicarbazones, heterocyclic moieties, and their metal (II) complexes. In this study, CS from crab shells is mixed with thiosemicarbazide (TSC). Then, imidazole-2-carboxaldehyde, oxazole-2-carboxaldehyde, and thiazole-2-carboxaldehyde reacted to make three different compounds from CS-TSC: [2a], [2b], and [2c]. The chemicals were mixed with nickel chloride to create nickel (II) chitosan 2-acetyl heterocyclic-2-thiosemicarbazone complexes. SEM and X-ray tests were performed on the powder, which showed that the nickel (II) chitosan thiosemicarbazone complexes had square and flat shapes. The synthesized compounds were tested to check their effectiveness in preventing MDCK and MCF-7. The study found that chitosan derivatives significantly inhibited MDCK and MCF-7.

Timosaponin AIII Disrupts Cell-Extracellular Matrix Interactions through the Inhibition of Endocytic Pathways.

Timosaponin AIII (TAIII), a steroidal saponin isolated from the root of Anemarrhena asphodeloides Bunge, exhibits various pharmacological activities, including anti-cancer properties. TAIII inhibits the migration and invasion of various cancer cell types. However, the mechanism underlying how TAIII regulates the motility of cancer cells remains incompletely understood. In this study, we demonstrate that TAIII disrupted cell-extracellular matrix (ECM) interactions by inhibiting internalization of cell surface proteins, such as integrins. We found that TAIII inhibited cell adhesion on various ECMs. Structure-activity relationship analysis demonstrated that TAIII exhibited unique activity among the saponins from Anemarrhena asphodeloides Bunge and that the number and position of saccharide moieties were important for TAIII to exert its activity. Time lapse imaging revealed that TAIII also suppressed cell spreading on the ECM, membrane ruffling, and lamellipodia formation. Furthermore, we examined integrin β1 behaviors in response to TAIII treatment and found that TAIII blocked its internalization. These findings contribute to delineating the potential molecular mechanisms by which TAIII exerts anti-metastatic activity.

Innovations in cancer diagnosis and treatment: prospects and challenges

The research relevance of cancer diagnostics and treatment is determined by its widespread occurrence and the lack of adequate modern diagnostic methods. The study aims to characterise new diagnostic methods, namely screenings in detecting cancer at early stages of development. To achieve this goal, the bibliosemantic and bibliographic methods were used. Main results. Cancer is the leading cause of morbidity and mortality after cardiovascular diseases and injuries in many countries around the world. Various diagnostic and treatment methods are used to combat this problem, including computed tomography, magnetic resonance imaging and positron emission tomography. In addition, modern diagnostic methods such as polymerase chain reaction, mass spectrometry and genomic sequencing play an important role in determining the types of cancer cells and their sensitivity to treatment. These advanced methods can be used to diagnose cancer more accurately and efficiently and choose the most appropriate treatment strategies for each patient. The practical significance of this topic is to ensure appropriate care for patients with cancer: providing high-quality, efficient, fast and minimally invasive diagnostics using the latest methods, as well as implementing a screening system.

Responsive Supramolecular Nanomicelles Formed through Self-Assembly of Acyclic Cucurbit[n]uril for Targeted Drug Delivery to Cancer Cells.

The supramolecular drug delivery systems (SDDSs) based on host-guest recognition through noncovalent interactions, capable of responsive behavior and dynamic switching to external stimuli, have attracted considerable attention in cancer therapy. In this study, a targeted dual-functional drug delivery system was designed and synthesized. A hydrophilic macrocyclic host molecule (acyclic cucurbit[n]uril ACB) was modified with folic acid (FA) as a targeting ligand. The guest molecule consists of a disulfide bond attached to adamantane (DA) and cannabidiol (CBD) at both ends of the response element of glutathione. Recognition and self-assembly of host and guest molecules successfully functionalize supramolecular nanomicelles (SNMs), targeting cancer cells and releasing drugs in a high glutathione environment. The interactions between host and guest molecules were investigated by using nuclear magnetic resonance (NMR), fluorescence titration, Fourier-transform infrared spectroscopy (FT-IR), and thermal analysis (TGA). Transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed the nanostructure of the SNMs. Experimentation with 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) demonstrated the responsiveness of SNMs to glutathione (GSH). In vitro cytotoxicity assays demonstrated that SNMs had a greater targeting efficacy for four types of cancer cells (HeLa, HCT-116, A549, and HepG2) compared to normal 293T cells. Cellular uptake studies revealed that HeLa cells more readily absorbed SNMs, leading to their accumulation in the tumor cell cytoplasm. Fluorescence colocalization assays verified that SNMs efficiently accumulated in organelles related to energy metabolism and signaling, including mitochondria and the endoplasmic reticulum, affecting cellular metabolic death. Both flow cytometry and confocal nuclear staining assays confirmed that SNMs effectively induced apoptosis over time, ultimately resulting in the death of cancer cells. These findings demonstrate that SNMs exhibit excellent targeting ability, responsiveness, high bioavailability, and stability, suggesting significant potential in drug delivery applications.

Two new guaiane-type sesquiterpene glycosides from Atractylodes Japonica Koidz. ex Kitam

Two new guaiane-type sesquiterpene glycosides, atractylodes guaianoside I (1) and atractylodes guaianoside II (2), along with eleven known sesquiterpenes (3–13), were isolated from Atractylodes Japonica Koidz. ex Kitam. The structures of these two new compounds were elucidated by extensive spectroscopic analyses and mass spectrometric techniques. And their absolute configurations were confirmed by electronic circular dichroism (ECD) calculations. In addition, the isolated compounds were evaluated for their cytotoxic activities against three cancer cell lines HT-29, A-549, and MCF-7. Results showed that new compound 2 had inhibitory effects on three types of cancer cells, while new compound 1 only had inhibitory effects on HT-29 and MCF-7.

Oncogenic accumulation of cysteine promotes cancer cell proliferation by regulating the translation of D-type cyclins

Malignant cells exhibit a high demand for amino acids to sustain their abnormal proliferation. Particularly, the intracellular accumulation of cysteine is often observed in cancer cells. Previous studies have shown that deprivation of intracellular cysteine in cancer cells results in the accumulation of lipid peroxides in the plasma membrane and induction of ferroptotic cell death, indicating that cysteine plays a critical role in the suppression of ferroptosis. Herein, we found that the oncogenic accumulation of cysteine also contributes to cancer cell proliferation by promoting the cell cycle progression, which is independent of its suppressive effect on ferroptosis. The growth ability of four types of cancer cells, including murine hepatocarcinoma cells, but not of primary hepatocytes, were dependent on the exogenous supply of cysteine. Deprivation of intracellular cysteine in cancer cells induced cell cycle arrest at the G0/G1 phase, accompanied by a decrease in the expression of cyclin D1 and D2 proteins. The cysteine deprivation-induced decrease in D-type cyclin expression was associated with the upregulation of eukaryotic translation initiation factor 4E binding protein (4E-BP1), which represses the translation of cyclin D1 and D2 proteins by binding to eukaryotic translation initiation factor 4E (eIF4E). Similar results were observed in hepatocarcinoma cells treated with erastin, an xCT inhibitor. These findings reveal an unappreciated role of cysteine in regulating the growth of malignant cancer cells and deepen our understanding of the cytotoxic effect of xCT inhibitor to prevent cancer cell proliferation.