Search Results (17,636)

Bufalin is a naturally occurring bufadienolide with broad-spectrum anticancer activity. Unlike conventional cytotoxic agents, bufalin exerts pleiotropic antitumour effects by directly modulating oncogenic proteins and promoting their degradation. It also disrupts metabolic plasticity, induces multiple forms of regulated cell death, counteracts therapeutic resistance, and remodels the immunosuppressive tumour microenvironment. However, the further application of bufalin is hindered by poor aqueous solubility, rapid systemic clearance, a narrow therapeutic window, and dose-limiting toxicity. Nanodrug delivery systems (NDDSs) offer a promising strategy for translating these interconnected pharmacological effects into spatially and temporally controlled therapeutic responses. This review summarises the distinctive anticancer mechanisms of bufalin and systematically evaluates the organic, inorganic, biomimetic, and hybrid nanocarriers developed for its delivery. Particular attention is given to tumour-responsive drug release, the targeting of cancer stem cells, the induction of ferroptosis and pyroptosis, metabolic modulation, sensitisation to phototherapy, and the activation of antitumour immunity. Finally, the major translational challenges are critically examined to inform the further rational development of bufalin-based nanomedicines. Full article

Cirsium japonicum is a medicinal plant traditionally used in East Asian medicine and contains multiple bioactive constituents with potential anticancer properties. This review critically evaluates the anticancer effects of C. japonicum and its associated constituents within the Hallmarks of Cancer framework. Evidence was classified as direct plant-specific evidence, constituent-based evidence, or contextual mechanistic evidence to distinguish findings obtained using botanical preparations from those generated using purified compounds derived from other sources. Direct studies of C. japonicum extracts, flavonoid fractions, phenylpropanoid glycosides, and C. japonicum var. maackii-mediated gold nanoparticles demonstrate antitumor, cytotoxic, antiangiogenic, immunomodulatory, and ferroptosis-associated activities, although target-level validation remains limited. Among its associated constituents, pectolinarigenin has the most developed mechanistic evidence, involving RRM2–CDK1, TOP2A, STAT3, and PI3K/AKT/mTOR signaling. Apigenin, luteolin, acacetin, linarin, cirsimaritin, and pectolinarin additionally influence regulated cell death, proliferative signaling, angiogenesis, metastasis, immune regulation, metabolic vulnerability, senescence, and therapy response. However, much of this evidence relies on pathway-associated changes rather than direct target engagement or genetic validation. Furthermore, the pharmacokinetics, systemic exposure, botanical standardization, tumor selectivity, and clinical relevance of these compounds remain insufficiently characterized. Future studies should prioritize standardized preparations, quantitative exposure analysis, functional target validation, clinically relevant models, and carefully designed combination strategies. Collectively, C. japonicum provides a promising multi-hallmark framework for anticancer investigation, but substantial translational evidence is still required before its therapeutic potential can be established. Full article

Ovarian cancer remains a major cause of gynecological cancer-related mortality, highlighting the need for novel therapeutic strategies capable of enhancing antitumor activity while targeting multiple mechanisms involved in tumor progression. Everolimus, an inhibitor of the mammalian target of rapamycin pathway, and carboplatin are established antineoplastic agents with distinct mechanisms of action, whereas astaxanthin is a bioactive carotenoid with antioxidant, anti-inflammatory, and potential anticancer properties. This study compared the individual and pairwise combination effects of carboplatin, everolimus, and astaxanthin on cell viability, migratory capacity, and inflammatory and tumor-associated biomarkers in SKOV3 ovarian cancer cells. Human SKOV3 ovarian cancer cells were cultured under standard conditions and exposed to different concentrations of carboplatin, everolimus, and astaxanthin, either individually or as pairwise two-drug combinations, for 24–72 h. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. Cell migration was evaluated using a scratch wound-healing assay. Based on the experimental treatment protocol, 100 nM everolimus, 100 μM carboplatin, and 100 μM astaxanthin, alone and in combination, were further evaluated for their effects on β-defensin 1, β-defensin 2, α-defensin 1, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) levels. Biomarker concentrations were determined by ELISA. Experiments were independently performed in triplicate. Everolimus, carboplatin, and astaxanthin produced concentration- and time-dependent alterations in SKOV3 cell viability, with more pronounced cytotoxic effects generally observed following prolonged exposure. The pairwise combination treatments also substantially affected cell viability, particularly at later experimental time points. Assessment of migratory capacity demonstrated significant differences in wound closure among treatment groups at 24, 48, and 72 h (p = 0.0224, p = 0.0155, and p = 0.0028, respectively), indicating a time-dependent inhibitory effect on SKOV3 cell migration. Treatment with carboplatin, everolimus, and astaxanthin, individually or in pairwise combinations, also significantly modulated β-defensin 1, β-defensin 2, α-defensin 1, TNF-α, and IL-1β levels compared with control cells, with the magnitude and direction of these changes varying according to treatment regimen and exposure duration. Everolimus, carboplatin, and astaxanthin exerted significant time- and treatment-dependent effects on the viability and migratory behavior of SKOV3 ovarian cancer cells and markedly modulated defensin and pro-inflammatory cytokine responses. The findings demonstrate distinct treatment- and time-dependent responses to the individual agents and their pairwise combinations in SKOV3 ovarian cancer cells. These observations represent preliminary comparative in vitro effects rather than evidence of pharmacological synergy or therapeutic benefit. Further mechanistic studies using additional ovarian cancer cell lines, formal drug interaction analyses, and in vivo models are required to establish the biological and potential therapeutic relevance of these treatment combinations. Full article

Lavandula multifida L., commonly known as Egyptian lavender or fern leaf lavender, is widely recognized and used as a medicinal plant throughout Mediterranean countries. While L. multifida has been extensively studied, research has largely centered on its essential oil, with limited data available on the composition and bioactivities of its organic extracts. This study characterized the phytochemical profiles of L. multifida extracts and evaluated their antioxidant capacity, effects on cancer cell viability, and antimicrobial activity using multiple in vitro assays. Phytochemical characterization included the quantification of total phenolic and flavonoid contents and HPLC/ESI-QTOF-MS profiling of methanolic (LM), aqueous (LAQ), and ethyl acetate (LEA) extracts. Antioxidant activity was assessed using four complementary in vitro assays (DPPH, ABTS, FRAP, and TAC). The effects of the extracts on cell viability were assessed using the MTT assay in human triple-negative breast cancer (MDA-MB-231) and colon adenocarcinoma (HCT116) cell lines, while antimicrobial activity was determined using the agar well diffusion and broth microdilution methods. Phytochemical profiling of L. multifida extracts revealed diverse metabolites dominated by fatty acids (mainly oxylipins), together with phenolic acids, flavonoids, terpenes, and other minor constituents. The methanolic extract showed the strongest DPPH scavenging effect (IC₅₀ = 14.19 µg/mL), LAQ showed the highest FRAP value (246.62 µg TE/mg), and LEA demonstrated the greatest ABTS (IC₅₀ = 28.07 µg/mL) and TAC (367.16 µg AAE/mg) activities. LEA also produced the greatest reductions in cell viability, reaching approximately 97% in HCT116 cells and 83% in MDA-MB-231 cells, with corresponding IC₅₀ values of 27.85 ± 2.48 and 63.71 ± 3.05 µg/mL, respectively. LM and LAQ showed the largest bacterial inhibition zones, while LEA, despite weaker diffusion activity, exhibited the greatest potency (MIC = 0.5–2 mg/mL; MBC = 0.5–5 mg/mL) and a unique antifungal effect (MIC = 2 mg/mL; MFC = 4 mg/mL). These findings underscore the potential of L. multifida extracts as a natural reservoir of bioactive compounds with notable antioxidant, anticancer, and antimicrobial activities, suggesting their relevance for future pharmaceutical development. Full article

The aryl hydrocarbon receptor (AHR) and the vitamin D receptor (VDR) were long regarded as independent transcription factors governing distinct physiology—xenobiotic sensing and calcium–vitamin D homeostasis, respectively. AHR, a basic helix–loop–helix/PAS protein, heterodimerizes with ARNT and binds xenobiotic response elements (XREs) to drive cytochrome P450 genes such as CYP1A1; VDR, a nuclear receptor activated by 1,25-dihydroxyvitamin D₃, heterodimerizes with RXR and binds vitamin D response elements (VDREs). Although their genes reside on separate chromosomes (AHR, Chr 7; VDR, Chr 12), an integrated view recognizes the two pathways as extensively cross-regulatory. This review synthesizes the molecular, immunological, and tissue-level evidence for VDR–AHR interplay. At the molecular level, the receptors cooperate at composite promoter architectures—most notably an everted-repeat VDRE positioned adjacent to an XRE in the CYP1A1 promoter—while AHR ligands reciprocally enhance CYP24A1-mediated catabolism of active vitamin D. Tryptophan metabolism provides a bidirectional hub: kynurenine and the UVB photoproduct FICZ serve as endogenous AHR ligands whose balance, modulated by VDR, shapes signaling output. The tumor suppressor p53 functions as a shared upstream regulator coupling genotoxic stress to both receptors, with convergence on the CDKN1A (p21) checkpoint. Functionally, AHR and VDR converge on the regulatory T cell (Treg)/Th17 axis to influence immune tolerance: sustained AHR activation by TCDD favors Foxp3⁺ Treg differentiation, transient FICZ-driven activation promotes Th17 responses, and VDR reinforces the tolerogenic arm while independently repressing IL-17. The receptors further cooperate in maintaining intestinal epithelial barrier integrity and NF-κB restraint, with parallel impairment in inflammatory bowel disease, and are co-activated in skin by solar UVB, which simultaneously generates vitamin D₃ and the AHR ligand FICZ within keratinocytes. In cancer, VDR acts as a tumor suppressor, AHR exhibits context-dependent pro- and anti-tumor roles, and a three-way AHR–VDR–p53 interaction—inverted by mutant p53—forms a critical regulatory node. Throughout, the direction and magnitude of cross-talk prove highly dependent on cell type, ligand identity and kinetics, and species—distinctions often underappreciated in the literature. Clarifying these context-specific determinants is essential for translating AHR–VDR cross-regulation into rational therapies in autoimmunity, mucosal inflammation, dermatology, and oncology. Full article

Bufadienolides are toad-derived cardiotonic steroids with anti-cancer activity; however, their Na⁺,K⁺-ATPase-mediated anti-cancer mechanisms remain incompletely understood. Here, we compared the anti-proliferative effects of six bufadienolides, bufalin (3β-bufalin), resibufogenin, cinobufagin, telocinobufagin, cinobufotalin, and desacetylcinobufagin, on human colorectal cancer HT-29 cells. Among them, only 3β-bufalin significantly suppressed cell proliferation in a concentration-dependent manner, with an IC₅₀ of 1.8 nM, whereas its hepatic metabolite, 3α-bufalin, showed markedly weaker activity, with an IC₅₀ of 488 nM. 3β-Bufalin inhibited Na⁺,K⁺-ATPase activity with an IC₅₀ of approximately 37 nM, indicating that it suppressed growth at concentrations lower than those required for pump inhibition. The Na⁺,K⁺-ATPase α1-isoform can function as a receptor-type (non-pumping) signaling platform linked to volume-regulated anion channel (VRAC) activation in membrane microdomains of cancer cells. 3β-Bufalin activated the VRAC with an EC₅₀ of 4.6 nM, whereas 3α-bufalin and the other bufadienolides showed no detectable activation. The pharmacological inhibition of the VRAC and the disruption of cholesterol-rich membrane microdomains significantly attenuated the anti-proliferative effect of 3β-bufalin. Furthermore, 3β-bufalin induced G2/M cell cycle arrest, which was attenuated by VRAC inhibition. These findings indicate that 3β-bufalin selectively suppresses cancer cell proliferation by coupling with receptor-type Na⁺,K⁺-ATPase to activate the VRAC in membrane microdomains rather than inhibiting Na⁺,K⁺-ATPase pump activity. Full article

Cytoplasmic stress granules (SGs) form in response to diverse insults; they are dismantled when the stress subsides. SG clearance is facilitated by molecular chaperones, nuclear transport factors, and other components. The anti-parasitic drug ivermectin inhibits nuclear trafficking and has potential anti-cancer activities. However, the molecular pathways that promote ivermectin’s therapeutic actions are poorly understood. Our study defined the effects of ivermectin on stress recovery in human neuroblastoma and cervical carcinoma cells. We demonstrate that ivermectin interferes with SG disassembly in neuroblastoma cells. The delay of SG dissolution is accompanied by significant changes in the proteostasis network. Notably, ivermectin diminishes de novo protein synthesis in unstressed and stressed cells. During recovery, ivermectin reduces the abundance of hsp70 in neuroblastoma, but not in cervical carcinoma cells. Surprisingly, ivermectin has no effect on Hsf1 abundance and localization. Moreover, ivermectin does not diminish the levels of transcripts encoding hsp70. Bioorthogonal Non-Canonical Amino Acid Tagging revealed that ivermectin markedly reduces the stress-induced de novo synthesis of hsp70 in neuroblastoma cells. Taken together, ivermectin can derail stress responses by a unique mechanism that alters the translation of hsp70 mRNA and is determined by the cellular context. This information is directly relevant to ivermectin-based anti-cancer therapies. Full article

Aptamer-functionalized liposomes are a promising strategy to improve the selectivity of anticancer therapies. AT11-L2 is a G-quadruplex (G4)-forming aptamer with high affinity for nucleolin (NCL), which is overexpressed at the surface of non-small cell lung cancer (NSCLC) cells. Here, we developed AT11-L2-functionalized liposomes loaded with doxorubicin (DOX) or BRACO-19 for targeted delivery to NSCLC cells. The effects of both compounds on AT11-L2 stability and the ability of the aptamer to retain G4 folding after liposome conjugation were evaluated. Liposomes were characterized for size, polydispersity, surface charge, stability, encapsulation efficiency, and release profile. Biological activity was assessed in A549 and MRC-5 cells. Liposomes had an average size of approximately 110 nm, with a slight size increase and reduced surface charge after AT11-L2 functionalization. The aptamer retained G4 folding in 100 mM KCl after conjugation. Encapsulation efficiency was approximately 90%. DOX showed substantial release within 72 h, whereas BRACO-19 exhibited a more sustained profile. AT11-L2-DOX liposomes showed preferential effects in A549 cells, while BRACO-19 formulations displayed lower selectivity and cytotoxicity. Additionally, the NCL-dependent internalization of AT11-L2-functionalized liposomes was supported by a protein-blocking assay using an anti-NCL antibody. These results support AT11-L2-functionalized liposomes as a versatile NCL-targeted delivery system for NSCLC. Full article

Psychoactive nitrogen-containing compounds represent a structurally diverse group of natural and synthetic molecules whose interactions with metal ions influence their physicochemical properties, biological activity, and analytical behavior. Although numerous studies have reported the synthesis of metal complexes, solution interactions, and metal-assisted analytical methods, the available knowledge remains scattered across compound classes and has not been comprehensively evaluated. This review summarizes advances in the coordination chemistry of psychoactive nitrogen-containing compounds from ScienceDirect, Google Scholar, and the Cambridge Structural Database (CSD), emphasizing donor atoms, coordination modes, structural diversity, crystallographic characterization, spectroscopic and computational investigations, and the biological properties of the resulting metal complexes. The current literature demonstrates that metal complexation can alter molecular geometry, electronic structure, redox behavior, biomolecular recognition, and pharmacological activity, while also offering opportunities to develop compounds with enhanced antimicrobial, anticancer, antioxidant, and DNA-binding properties. By integrating coordination behavior, structural, and biological aspects within a single framework, this review highlights the central role of metal interactions in psychoactive compounds and identifies emerging opportunities to develop advanced analytical methodologies and functional metal-based systems. Full article

Resveratrol (RSV) is a naturally occurring polyphenol with well-documented antioxidant, anti-inflammatory, antimicrobial, photoprotective, wound-healing, depigmenting, and anticancer properties, making it an attractive candidate for dermocosmetic and dermatological applications. However, its clinical translation into effective topical products remains limited by poor aqueous solubility, chemical instability, photoisomerization, rapid cutaneous metabolism, and restricted skin penetration, all of which compromise local bioavailability and therapeutic efficacy. This narrative review critically examines the molecular mechanisms underlying the cutaneous effects of RSV and discusses how its physicochemical and pharmacokinetic characteristics influence topical performance. Particular emphasis is placed on advanced delivery strategies developed to overcome these limitations, including lipid-based nanocarriers, polymeric nanoparticles (NPs), nanofibers, inorganic nanocarriers, microneedles, hydrogels, and other emerging delivery platforms. The mechanisms by which these systems improve RSV solubility, stability, controlled release, skin retention, and dermal penetration are critically evaluated together with their reported therapeutic outcomes. Although advanced delivery systems have consistently improved the topical performance of RSV in preclinical studies, clinical evidence remains limited. To date, only one published placebo-controlled clinical trial has specifically evaluated topical RSV as the active ingredient, and none of the advanced RSV-nanocarrier platforms discussed in this review has undergone clinical evaluation. Bridging this substantial translational gap will require not only further optimization of formulation design but also scalable manufacturing, rigorous clinical validation, and regulatory pathways capable of supporting the development of safe, effective and evidence-based next-generation dermocosmetic and dermatological products. Full article

Matrix metalloproteinases (MMPs) have long been recognized as key mediators of tumor invasion and metastasis due to their capacity to degrade extracellular matrix components. However, clinical failure of broad-spectrum MMP inhibitors has revealed a more complex and context-dependent role for these proteases in cancer. Among them, macrophage metalloelastase, MMP-12, has emerged as a particularly intriguing enzyme with both tumor-promoting and tumor-suppressive functions. Predominantly expressed by tumor-associated macrophages, MMP-12 occupies a unique position at the interface of proteolysis, inflammation, and immune regulation within the tumor microenvironment. Accumulating evidence from experimental models and clinical studies demonstrates that MMP-12 can exert potent anti-tumorigenic effects, primarily through inhibition of angiogenesis. Mechanistically, MMP-12 generates angiostatin and other anti-angiogenic fragments, suppresses vascular endothelial growth factor signaling, and reduces tumor vascularization, thereby limiting tumor growth and metastatic expansion. In several cancer types, including lung, colorectal, and hepatocellular carcinoma, elevated MMP-12 expression has been associated with reduced tumor progression and improved patient outcomes. Conversely, MMP-12 can also promote tumor progression through extracellular matrix remodeling, facilitation of invasion, and modulation of inflammatory pathways, particularly in environments characterized by chronic inflammation or immunosuppressive macrophage phenotypes. These seemingly contradictory roles are governed by multiple context-dependent factors, including macrophage polarization, tumor type, disease stage, and microenvironmental cues such as hypoxia and cytokine signaling. In this review, we comprehensively examine the molecular regulation, functional mechanisms, and clinical relevance of MMP-12 in cancer. We highlight the dualistic nature of MMP-12 activity and discuss its implications for therapeutic strategies, emphasizing the need for selective and context-aware targeting approaches rather than broad inhibition of MMP activity. Full article

Cancer remains a leading cause of global mortality, entailing the exploration of novel therapeutic agents from natural sources. This study evaluated the in vitro anti-cancer potential of essential oils (EOs) extracted from the needles of Pinus sylvestris L. (Scots pine) and Picea abies (L.) H. Karst. (Norway spruce). GC–MS analysis revealed that both EOs are rich in monoterpenes; the primary constituents were α-pinene (35.27%) for Pinus sylvestris sylvestris EO (Pinus EO) and β-pinene (31.40%) for Picea abies EO (Picea EO). Cell viability assay (Alamar Blue) demonstrated that both EOs exert a dose-dependent cytotoxic effect across all tested malignant lines: melanoma (A375), colorectal adenocarcinoma (HT-29), and pancreatic adenocarcinoma (PANC-1). Notably, Pinus EO consistently displayed higher potency toward cancer cells when compared with normal keratinocytes (HaCaT), with the highest selectivity noticed in HT-29 cells. Immunofluorescence analysis revealed morphological changes consistent with apoptosis, such as nuclear condensation, DNA fragmentation, and the disruption of the β-actin cytoskeleton. High-resolution respirometry indicated that the EOs increase LEAK respiration, while also significantly reducing the oxidative phosphorylation (OXPHOS) efficiency. Furthermore, network pharmacology and molecular docking predicted EP300 as a common hub target for both EOs, with β-caryophyllene showing the most favourable predicted binding affinity among the investigated constituents. Overall, these preliminary in vitro and in silico findings support the further investigation of Pinus EO and Picea EO as potential candidates for the development of future adjuvant strategies in cancer therapy. Full article

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor clinical outcomes and limited responsiveness to conventional treatments. Beyond delayed diagnosis, its high mortality is linked to limited treatment choices and resistance to chemotherapy. Neoplastic cells characterized by stem-like features and epithelial–mesenchymal transition (EMT) activation are crucial drivers of drug resistance and metastatic progression. Consequently, targeting these cellular programs could represent a promising therapeutic strategy for PDAC. N-acetyl-L-aspartic acid (NAA) is an endogenous metabolite, mainly localized in the central nervous system, where it facilitates acetate storage for lipid metabolism. Previous studies established its antineoplastic effect in neuroblastoma, promoting a more differentiated phenotype of cancer cells. Here we investigated the effects of NAA on BxPC-3 pancreatic cancer cells using both 2D and 3D models. NAA treatment induced a dose-dependent reduction in cell proliferation and led to a significant downregulation of stemness-associated surface markers, with concomitant upregulation of E-cadherin. Furthermore, NAA significantly enhanced cellular radiosensitization with a reduction in caveolin-1 and increased efficacy of gemcitabine in PDAC cells. Collectively, these results confirmed the anticancer activity of NAA and provide a rationale for further investigation of its synergistic effects with radiotherapy to yield better PDAC treatments. Full article

Cancer is still one of the major causes of death globally. While there are many cancer therapies, they often come with significant adverse effects and limitations. A lot of studies have shown that using natural products can improve the efficacy of conventional therapies and decrease their toxicity. Natural products and their derivatives encompassing unmodified molecules, semi-synthetic analogs, and synthetic structures featuring natural pharmacophores, represent a major foundation for approved anticancer agents. Phenolic compounds are a large family of naturally occurring compounds found in plants and have attracted a lot of attention for their potential anticancer properties. Preclinical studies have shown that phenolic compounds have anticancer activity through different mechanisms, mainly by modulating inflammation, which plays a critical role in cancer development. Inflammatory processes in cancer involve complex molecular mechanisms regulated by both oncogenic and tumor-suppressing transcription factors. This review focuses on how phenolic compounds regulate transcription factors, such as nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), and signal transducer and activator of transcription 3 (STAT3), which are critical in cancer-related gene expression, ultimately leading to the inhibition of cancer cell proliferation, invasion, and metastasis. Furthermore, phenolic compounds have been shown to synergize with conventional anticancer drugs, enhancing their efficacy and reducing side effects. This review investigates the role of phenolic compounds in regulating transcription factors in cancer animal models, highlighting both the therapeutic potential and limitations of these compounds in cancer prevention and treatment. Full article

Background/Objectives: Oxidative stress, chronic inflammation, disrupted apoptosis, and altered autophagy are biological processes implicated in colorectal tumor development. Morin is a plant-derived flavonoid with antioxidant and anti-inflammatory properties, but its limited solubility and bioavailability may limit its biological activity. This study evaluated the effects of free morin and morin-loaded liposomes (MOR-Lips) on 1,2-dimethylhydrazine (DMH)-associated colonic biochemical, molecular, and histopathological alterations in rats. Methods: Rats were randomly assigned to six groups—vehicle control, MOR, MOR-Lips, DMH, DMH + MOR, and DMH + MOR-Lips—and treated for 10 weeks. Serum and colonic tissues were evaluated for cancer-associated biomarkers (CEA, CA19-9, CA125, HMG-CoA reductase), oxidative stress and antioxidant indices, nitrosative and oxidative DNA-damage markers (MDA, NO, 8-OHdG), inflammatory mediators (TLR4/NF-κB/COX-2, cytokines, MPO), proliferative indices (Ki-67, PCNA), apoptotic and autophagy-related regulators (Bax, caspase-3, p53, cytochrome c, BCL-2, p-AKT, LC3-II, Beclin-1, p62), and histopathological and immunohistochemical changes. Results: DMH exposure was associated with increased CEA, CA19-9, CA125, HMG-CoA reductase, MDA, NO, 8-OHdG, TLR4/NF-κB/COX-2, cytokines, MPO, Ki-67, and PCNA. DMH also reduced NRF2/HO-1 signaling and antioxidant defenses, shifted apoptosis-related markers toward a pro-survival profile, altered autophagy-related markers, and produced marked colonic histopathological abnormalities. Both free MOR and MOR-Lips attenuated several of these DMH-associated alterations, with MOR-Lips generally producing greater effects than free MOR. MOR-LIP treatment was associated with restoration of antioxidant marker profiles, reduced levels of inflammatory and proliferative markers, a shift toward a pro-apoptotic marker profile, partial normalization of autophagy-related markers, and improved colonic histopathological appearance. Conclusions: In DMH-exposed rats, MOR-Lips were associated with more favorable redox, inflammatory, proliferative, apoptosis-related, autophagy-related, and histopathological profiles than free MOR. These findings support further investigation of MOR-Lips as a formulation strategy for improving the biological activity of morin. Because quantitative preneoplastic and neoplastic endpoints were not measured, the results do not establish inhibition of colorectal carcinogenesis or chemopreventive efficacy. Full article