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BACKGROUND: Active components from natural fungal products have shown promising potential as anti‐tumor therapeutic agents. In the search for anti‐tumor agents, research to overcome the drawbacks of high molecular weight and low bioavailability of pure polysaccharides, polysaccharide‐conjugated selenium nanoparticles (SeNPs) has attracted much attention. RESULTS: A novel polysaccharide‐selenium nanoparticle complex was produced, in which SeNPs were decorated with polysaccharide obtained from fermented mycelia broth of Lactarius deliciosus (FLDP). Transmission electron microscope, dynamic light scattering, and X‐ray photoelectron spectroscopy were utilized to characterize the FLDP‐SeNPs; and human hepatocarcinoma cell line (HepG2) was used to assess growth inhibition efficacy. The FLDP‐SeNPs that were prepared had a spherical shape with the smallest mean diameter of 32 nm. The FLDP‐SeNPs showed satisfactory dispersibility and stability after combination, demonstrating that a reliable consolidated structure had formed. The results revealed that FLDP‐SeNPs had notable growth inhibition effects on HepG2 cells. They reduced the membrane potential of mitochondria significantly, increased the generation of reactive oxygen species, enhanced levels of both Caspase‐3 and Caspase‐9, and led to the nucleus in a wrinkled form. CONCLUSION: The FLDP‐SeNPs could exert a synergetic toxicity reduction and inhibition enhancement effect on HepG2 cells by inducing early apoptosis, through mitochondria‐mediated cytochrome C‐Caspases and reactive oxygen species‐induced DNA damage pathways. These results indicate that FLDP‐SeNP treatment of HepG2 cells induced early apoptosis with synergetic efficacy, showing that FLDP‐SeNPs can be useful as natural anti‐tumor agents. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Cisplatin is a widely used antineoplastic drug for treating various types of cancers. However, it can cause severe side effects, such as bilateral and irreversible hearing loss, which significantly impacts quality of life. Ferroptosis, an iron-dependent form of programmed cell death, has been implicated in the pathogenesis of cisplatin-induced ototoxicity. Here, we investigated the effects of nuciferine, a natural active ingredient isolated from lotus species, on the ferroptosis of cochlear hair cells. Firstly, our results demonstrated that nuciferine can protect hair cells against RSL3-induced and cisplatin-induced damage. Secondly, nuciferine treatment reduced ferrous iron (Fe2+) overload in cochlear hair cells via inhibiting NCOA4-mediated ferritinophagy. Inhibition of ferritinophagy by knocking down Ncoa4 alleviated cisplatin-induced ototoxicity. Importantly, nuciferine treatment mitigated cochlear hair cell loss and damage to ribbon synapse, and improved mouse hearing function in an acute cisplatin-induced hearing loss model. Our findings highlight the role of NCOA4-mediated ferritinophagy in the pathogenesis of cisplatin-induced ototoxicity and provide evidence for nuciferine as a promising protective agent for treating cisplatin-induced hearing loss. [ABSTRACT FROM AUTHOR]

π‐π interactions, serving as a pivotal driving force, hold enduring significance in the realm of drug delivery system development, primarily due to the prevalence of aromatic moieties in a substantial number of clinically relevant pharmaceutical compounds. Herein, we constructed a novel carbon nitride compound called PTCNx, featuring a large π‐conjugated skeleton, and employed it as a carrier for delivering aromatic clinical drugs for the first time. We conducted sequence characterization of their chemical structure, optical properties, and morphology, along with extensive research to analyze their significant enhancement in drug loading capacity. Of particular note was the exceptional loading efficiency of Doxorubicin (DOX) under alkaline conditions, achieving an unexpected 99 % efficacy, significantly surpassing the capabilities of traditional carbon nitrides with limited π‐conjugated systems. Cell tests illustrated that PTCN550 carrier exhibited favorable biocompatibility and low toxicity for normal and tumor cells, showing its potential as a drug carrier. However, PTCN550‐DOX complex effectively inhibited both A549 and CNE‐2Z tumor cells. And it demonstrated more effective anti‐tumor activity for CNE‐2Z than for A549 cells. This study marks a significant milestone, representing the inaugural endeavor to elucidate the improvement in loading capacity through the strategic extension of the π‐conjugated system design paradigm. [ABSTRACT FROM AUTHOR]

Graphite carbon nitride (g-C3N 4) polymer with two-dimensional planar structure is a new star in nanodrug delivery systems in recent years because it shows characteristics of low cost, nontoxicity, biocompatibility and easy functionalization. However, conventional g-C3N4 shows bulk, macro size, small specific surface area and poor water solubility. To improve this, most works are always confined to physical ultrasound, oxidative peeling or template-strategy, which have the disadvantages of redundant steps, environment-unfriendliness and high cost. In this paper, a modified supramolecular self-assembled strategy was carried out to construct a novel graphitic carbon nitride nanoplatform (named by CA-MA X) using melamine and cyanuric as precursors. The chemical structure characterization, drug loading experiment and cell tests in vitro of the CA-MA X nanoplatform were carried out and discussed in detail. Results indicated that the obtained samples show enhanced specific surface area, more exposed groups and good biocompatibility. Compared to the traditional carbon nitride (named by MA-CN), the newly prepared CA-MA X carrier shows improved drug loading efficiency and good pH-responsive loading, as well as releasing. Cell uptake experiment demonstrates that CA-MA2-DOX can be swallowed by cancer cells and during treatment of the cancer cell process, the CA-MA2-DOX complex experiences phagocytizing by the cancer cell, controlled-release DOX and kills the cancer cell after DOX was passively diffused into the nucleus. CA-MA2-DOX exhibited significant in vitro antitumor activity. To our knowledge, this is the first time the supramolecular self-assembled method was used in carbon nitride nanocarrier construction for cancer treatment. g-C3N4 nano-platform was prepared via supramolecular self-assembly strategy, which is used as drug delivery for the first time to deliver small molecule drugs for cancer therapy. The obtained samples show higher specific surface area (78.9 m2/g), more exposed groups and good biocompatibility, making it more suitable to be used as drugs carrier. Compared to the traditional g-C3N4, it shows improved encapsulation efficiency, good pH response and a significant in vitro antitumor activity. [ABSTRACT FROM AUTHOR]

Perioperative or postoperative adjuvant chemotherapy based on 5-fluorouracil (5-FU) is a common first-line adjuvant therapy for gastric cancer (GC). However, drug resistance and the side effects of 5-FU have reduced its efficacy. Among these side effects, gastrointestinal (GI) toxicity is one of the most common. Xianglian Pill (XLP) is a Chinese patent medicine that is commonly used for the treatment of diarrhoea. It can reduce inflammation and has a protective effect on the intestinal mucosa. Recent studies have shown that many components of XLP can inhibite tumor cell growth. However, the therapeutic effect of XLP in combination with 5-FU on GC is unclear. To investigate whether the combination of XLP and 5-FU can enhance anti-GC activity while reducing GI toxicity. XLP was administered orally during intraperitoneal injection of 5-FU in GC mice model. Mice were continuously monitored for diarrhea and xenograft tumor growth. After 2 weeks, the mice were sacrificed and serum was collected to determine interleukin-6 levels. Pathological changes, the expression of pro-inflammatory factors and p38 mitogen-activated protein kinase (MAPK) in GI tissue were determined by Western blot analysis. Pathological changes, apoptosis levels and p38 MAPK expression levels in xenograft tissues were also determined. The results showed that XLP could alleviate GI mucosal injury caused by 5-FU, alleviated diarrhea, and inhibited the expression of nuclear factor (NF)-κB and myeloid differentiation primary response-88. Besides, XLP could promote the 5-FU-induced apoptosis of GC cells and enhance the inhibitory effect of 5-FU on tumor xenografts. Further study showed that XLP administration could regulate the expression of p38 MAPK. XLP in combination with 5-FU could alleviate its GI side effects and enhance its inhibitory effect on xenograft tumor. Moreover, these effects were found to be related to the regulation of the p38 MAPK/NF-κB pathway. [Display omitted] • XLP combined with 5-FU could alleviate the diarrhea and reduce the inflammation of gastrointestinal mucosa in GC mice model. • XLP combined with 5-FU could inhibit the growth of xenogaft and promote tumor cell apoptosis in GC mice model. • Those effects were related to the regulation of p38MAPK/NF-κB signaling pathway by XLP. [ABSTRACT FROM AUTHOR]

Chemotherapy, the most common class of anticancer drugs, is considerably limited owing to its adverse side effects. In this study, we aimed to evaluate the protective effect and mechanism of action of large-leaf yellow tea polysaccharides (ULYTP-1, 1.29 × 104 Da) against chemotherapeutic 5-fluorouracil (5-Fu). Structural characterisation revealed that ULYTP-1 was a β-galactopyranouronic acid. Furthermore, ULYTP-1 promoted autolysosome formation, activating autophagy and reducing the oxidative stress and inflammation caused by 5-Fu. Our in vivo study of 4 T1 tumour-bearing mice revealed that ULYTP-1 also attenuated 5-Fu toxicity through modulation of the gut microbiota. Moreover, ULYTP-1 effectively protected immune organs and the liver from 5-Fu toxicity, while promoting its tumour-inhibitory properties. The current findings provide a new strategy for optimising chemotherapy regimens in the clinic. [Display omitted] • Polysaccharide ULYTP-1 was extracted from large-leaf yellow tea. • ULYTP-1 is a β-galactopyranouronic acid with a spongy steric configuration. • ULYTP-1 activates autophagy to alleviate 5-fluorouracil-induced liver injury. • ULYTP-1 alleviated gut dysbiosis in 4 T1 tumour-bearing mice. [ABSTRACT FROM AUTHOR]

OSMAC strategy is a useful tool for discovering series of metabolites from microorganism. Five new sambutoxin derivatives (1 – 2 , 4 , 8 – 9), together with seven known compounds (3 , 5 – 7 , 10 – 12), were isolated from Talaromyces sp. CY-3 under OSMAC strategy and guidance of molecular networking. Their planar structures and absolute configurations were determined by NMR, HRESIMS, ECD spectra and common biosynthetic pathway. In bioassay, compounds 1 – 12 showed cytotoxicity to tumor cell lines with IC 50 values in the range of 1.76–49.13 μM. The antitumor molecular mechanism of 10 was also explored. In vitro compound 10 significantly inhibited the growth and proliferation of two lung cancer cell lines (A549 and H1703). Furthermore, colony formation, EdU analysis, flow cytometry and Western blot analysis showed that 10 could induce cell cycle arrest in G0/G1 phase by promoting the expression of p53 and p21. The molecular mechanism of its antitumor effects in vitro is that 10 arrests the cell cycle by activating the p21/CyclinD1/Rb signaling pathway and the p53 pathway. Our results identified a lead small molecule compound with efficient antitumor growth and proliferation activity. [Display omitted] • Five new 2-hydroxy-4-pyridone derivatives were isolated from Talaromyces sp. CY-3. • Compound 1 represents of the first sambutoxin with 7 R and 11 S configurations. • SARs of sambutoxins on cytotoxicity to tumor cell lines were discussed. • 10 arrests the cell cycle by activating the p21/CycinD1/Rb signaling pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel pyroptosis inducers with anti-tumor activity were discovered. • Efficient synthesis of 1H-benzo[ e ]indole-2(3H)-one spirocyclic compounds by a green, "one-pot" method using water as solvent. • A promising anti-tumor candidate compound A9. Pyroptosis induction is anticipated to be a new approach to developing anti-tumor medications. A novel class of spirocyclic compounds was designed by hybridization of 1H-Benzo[ e ]indole-2(3H)-one with 1,4-dihydroquinoline and synthesized through a new green "one-pot" synthesis method using 10 wt% SDS/H 2 O as a solvent to screen novel tumor cell pyroptosis inducers. The anti-tumor activity of all compounds in vitro was determined by the MTT method, and a fraction of the compounds showed good cell growth inhibitory activity. The quantitative structure–activity relationship models of the compounds were established by artificial intelligence random forest algorithm (R2 = 0.9656 and 0.9747). The ideal compound A9 could, in a concentration-dependent manner, prevent ovarian cancer cells from forming colonies, migrating, and invading. Furthermore, A9 could significantly induce pyroptosis and upregulate the expression of pyroptosis-related proteins GSDME-N, in addition to inducing apoptosis and mediating the expression of apoptosis-related proteins in ovarian cancer cells. A9 (5 mg/kg) significantly reduced tumor volume and weight of ovarian cancer in vivo , decreased caspase-3 expression in tumor tissue, and induced the production of GSDME-N. This study provides a green and efficient atom-economic synthesis method for 1H-Benzo[ e ]indole-2(3H)-one spirocyclic derivatives and a promising pyroptosis inducer with anti-tumor activity. [ABSTRACT FROM AUTHOR]