Linalool is a naturally occurring volatile monoterpene that exhibits significant anticancer potency across several malignancies via multitargeted molecular mechanisms. However, the translational research requires a clear anticancer potency with molecular targets and bioavailability data with respect to cancer type as identified via adequate cell and animal models, which lead to clinical trials. Nevertheless, the translation of linalool for clinical use is restricted by the lack of clinical trials and its limited in vivo bioavailability as reported in pre-clinical studies, high volatility and poor aqueous solubility. Therefore, this review examines the reported anticancer potency, probable molecular mechanisms, bioavailability research findings, and current nanoformulation of linalool for future application as an effective medicine. Inadequate in vivo validation and limited intravenous delivery data further highlight the need for advanced nanoformulation techniques and thorough translational studies. The literature for this review was methodically collected from research findings published between 2000 and 2025, capturing foundational and current breakthroughs on linalool’s anticancer potency. A higher anticancer potency as indicated by low IC50 values in leukaemia, cervical, oral, and prostate cancer cells and a relatively lower anticancer potency in more resistant models like lung and colorectal malignancies were observed from the research reports. Linalool exerted this anticancer potency in both in vitro and in vivo studies through modulation of many molecular activities and signalling pathways as evidenced by both in vitro and in vivo studies, which is supported by the binding affinity of Linalool towards the signalling proteins observed in the in silico molecular docking studies. The cytotoxicity studies have reported insignificant level of toxicity toward non-cancerous cells, but this evidence is limited to specific experimental models. Advances in nanoformulation, including lipid- and gold-based nanoparticles, have improved linalool’s in vivo stability, bioavailability, targeted distribution, and thus anticancer activity, with a reduction in toxicity in the pre-clinical models. Linalool thus shows consistent multi-pathway targeted anticancer activity in vitro and in vivo, and nanocarrier formulations offer a promising strategy to address its physicochemical limitations; however, given the scarcity of pharmacokinetic, toxicity, and clinical efficacy data in humans, substantial translational and clinical research is needed before its therapeutic potential can be established.
Although oxaliplatin (OXA) is widely used in the treatment of colon cancer, there is a need for more effective and safer treatment approaches due to the development of treatment-related resistance, limited therapeutic efficacy, and significant side effects. In recent years, combination therapy strategies have shown promise in cancer research due to their potential to improve chemotherapy outcomes. In this study, we aimed to evaluate the effects of OXA-based electrochemotherapy (ECT) and its supplementation with 1α,25-dihydroxyvitamin D3 on cell viability, apoptotic response, intracellular survival signaling, and energy dynamics in human colon cancer cell lines. The effects of single and combined treatment applications on cell viability were evaluated using the MTT test. Apoptotic response was analyzed by caspase-3 activity measurement and Annexin V/PI flow cytometry. Intracellular survival signaling pathways Phosphatidylinositol 3-kinase (PI3K), Protein kinase C (PKC), and Nuclear factor kappa (NF-κB) protein levels were measured using ELISA, while cellular energy status was determined by luminescence-based ATP analysis. OXA treatment alone reduced cell viability in a dose-dependent manner. 25 µM OXA treatment increased caspase-3 activity while causing a decrease in PI3K, PKC, and NF-κB protein levels. In ECT treatment, the decrease in cell viability occurred at lower OXA doses. Accordingly, the decrease in PI3K, PKC, and NF-κB protein levels was significantly lower compared to the control group. In ECT treatment with 1α,25-dihydroxyvitamin D3, the decrease in viability became more pronounced, and the IC50 value decreased from 138.66 µM for OXA alone to 26.30 µM with the combined treatment. On the other hand, survival markers PI3K, PKC, and NF-κB protein levels showed a dramatic decrease, while total ATP levels increased. In conclusion, ECT therapy supplemented with 1α,25-dihydroxyvitamin D3 significantly enhanced the cytotoxic effect compared to OXA therapy alone, by inducing caspase-3 activation and suppressing the PI3K/PKC/NF-κB signaling pathways. Furthermore, the increase in ATP levels suggests that the combined therapy may reprogram cellular energy metabolism. However, it should be noted that further molecular and in vivo studies are needed to understand the therapeutic mechanisms and sustainability of these effects.
Bladder urothelial carcinoma (BUC) is associated with poor prognosis and chemoresistance. The RNA-binding protein IGF2BP3 has been implicated in the progression and drug resistance of various cancers, but its role in UC remains underexplored. This study aimed to investigate the role of IGF2BP3 in regulating CENPA mRNA stability and its contribution to UC malignancy and paclitaxel (PTX) resistance. We analyzed human BUC cell lines (UMUC3, T24) and their paclitaxel-resistant counterpart (T24/R). The interaction between IGF2BP3 and CENPA mRNA was assessed using RNA immunoprecipitation (RIP), MeRIP-qPCR, and dual-luciferase reporter assays. RNA stability was measured with actinomycin D treatment. Cell migration, invasion, and clonogenic assays were performed to evaluate the impact of IGF2BP3 and CENPA modulation on tumor behavior. In vivo tumorigenicity and paclitaxel response were evaluated using xenograft mouse models. IGF2BP3 directly binds to m6A-modified CENPA mRNA and enhances its stability, thereby sustaining its expression in BUC. IGF2BP3 knockdown markedly decreased CENPA mRNA and protein levels and increased paclitaxel sensitivity. CENPA overexpression restored the migratory, invasive, and clonogenic capacities of IGF2BP3-silenced cells under paclitaxel treatment, whereas mutation of the m6A site abolished this rescue effect, indicating m6A dependency. In vivo, IGF2BP3 silencing suppressed tumor growth and enhanced paclitaxel sensitivity in T24/R-derived xenografts, which was partially reversed by CENPA overexpression. IGF2BP3 promotes malignant phenotype and paclitaxel resistance in BUC by stabilizing CENPA mRNA. Targeting the IGF2BP3-CENPA axis may provide a novel therapeutic strategy to overcome chemoresistance in BUC.
Ginger (Zingiber officinale) is a common spice with therapeutic potential due to its bioactive compounds and was used for the green synthesis of ginger-derived silver nanoparticles (G-AgNPs). The cytotoxic, antioxidant, and pro-apoptotic effects of the synthesized G-AgNPs were evaluated against HepG-2, MCF-7, and WI-38 cell lines. Gas chromatography–mass spectrometry (GC–MS) analysis identified 36 phytochemicals, with major components including α-zingiberene (37.88
Head and neck squamous cell carcinoma (HNSCC) remains a challenge due to recurrence, metastasis, and resistance to conventional therapies, particularly in human papillomavirus (HPV)-negative tumors. Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has demonstrated antitumor activity in several cancer models; however, its effects in chemoresistant HNSCC are not well established. This study evaluates the antitumor effects of CBD and cellular mechanisms in a cisplatin -resistant, HPV-negative HNSCC model. Cytotoxic effects of CBD were assessed in HN13 cells and compared with fibroblasts and keratinocytes using MTT and selectivity index analysis. Migration, invasion, metalloproteinase activity, clonogenic survival, and cytotoxicity on 3D spheroids were evaluated. Cell death-related mechanisms were investigated using acridine orange/propidium iodide staining and Western blot analysis of apoptosis, autophagy, and cell-cycle regulation. Antitumor activity and vascular safety were further assessed using the chorioallantoic membrane model and HET-CAM assay. The combined effect of CBD and CIS was evaluated using the combination index analysis. CBD exhibited selective cytotoxicity toward HN13 cells and reduced migration, invasion, matrix metalloproteinase-2/9 activity, clonogenic survival, and 3D spheroid growth. CBD altered proteins associated with apoptosis, autophagy, and cell-cycle regulation. Pharmacological inhibition with 3-MA enhanced CBD-associated apoptotic signaling, increasing PARP and caspase-3 cleavage. In the CAM, CBD reduced tumor growth and vascular area without inducing vascular irritation. Furthermore, CBD and CIS demonstrated synergistic cytotoxic effects in HN13 cells. CBD exerted selective antitumor effects on CIS-resistant HN13 HNSCC cells, affecting tumor-associated behaviors and modulating apoptosis and autophagy-related signaling, while acting synergistically with cisplatin. These findings support further preclinical investigation of CBD as a potential adjunct approach in HNSCC, particularly in chemoresistant settings.
