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Lonicerae Japonicae Flos (LJF, called Jinyinhua in China), comes from the dried flower buds or flowers to be opened of Lonicera japonica Thunb. in the Lonicera family. It has a long history of medicinal use and has a wide range of application prospects. As modern research advances, an increasing number of scientific experiments have demonstrated the anticancer potential of LJF. However, there is a notable absence of systematic reports detailing the anti-tumor effects of LJF. This review integrates the principles of Traditional Chinese Medicine (TCM) with contemporary pharmacological techniques, drawing upon literature from authoritative databases such as PubMed, CNKI, and WanFang to conduct a comprehensive study of LJF. Notably, a total of 507 compounds have been isolated and characterized from the plant to date, which include volatile oils, organic acids, flavonoids, iridoids, triterpenes and triterpenoid saponins. Pharmacological studies have demonstrated that LJF extract, along with components such as chlorogenic acid, luteolin, rutin, luteoloside, hyperoside and isochlorogenic acid, exhibits potential anticancer activities. Consequently, we have conducted a comprehensive review and summary of the mechanisms of action and clinical applications of these components. Furthermore, we have detailed the pharmacokinetics, quality control, and toxicity of LJF, while also discussing its prospective applications in the fields of biomedicine and preventive healthcare. It is hoped that these studies will provide valuable reference for the clinical research, development, and application of LJF. [ABSTRACT FROM AUTHOR]

The incidence of common gynecological malignancies remains high, with current treatments facing multiple limitations and adverse effects. Thus, continuing the search for safe and effective oncologic treatment strategies continues. Resveratrol (RES), a natural non-flavonoid polyphenolic compound, is widely found in various plants and fruits, such as grapes, Reynoutria japonica Houtt., peanuts, and berries. RES possesses diverse biological properties, including neuroprotective, antitumor, anti-inflammatory, and osteoporosis inhibition effects. Notably, RES is broadly applicable in antitumor therapy, particularly for treating gynecological tumors (cervical, endometrial, and ovarian carcinomas). RES exerts antitumor effects by promoting tumor cell apoptosis, inhibiting cell proliferation, invasion, and metastasis, regulating tumor cell autophagy, and enhancing the efficacy of antitumor drugs while minimizing their toxic side effects. However, comprehensive reviews on the role of RES in combating gynecological tumors and its mechanisms of action are lacking. This review aims to fill this gap by examining the RES antitumor mechanisms of action in gynecological tumors, providing valuable insights for clinical treatment. [ABSTRACT FROM AUTHOR]

Embelin, a natural para-benzoquinone product, is derived from plants of the Embelia genus, particularly Embelia ribes Burm.f. A staple in traditional medicinal formulations for centuries, Embelin's pharmacological actions are attributed to the hydroxyl benzoquinone present in its structure. Its therapeutic potential is bolstered by unique physical and chemical properties. Recently, Embelin, recognized as a non-peptidic, cell-permeable small inhibitor of the X-linked inhibitor of apoptosis protein (XIAP), has garnered significant attention for its anticancer activity. It demonstrates various anticancer mechanisms, such as apoptosis induction, cell cycle arrest, and autophagy, in different cancer types. Additionally, Embelin modulates several signal transduction pathways, including NF-κB, PI3Kinase/AKT, and STAT3, effectively inhibiting the proliferation of diverse cancer cell lines. This literature review illuminates the anticancer potential of Embelin, detailing its mechanisms of action and prospective clinical applications, based on relevant scientific literature from the past decade sourced from various electronic databases.

The Janus kinase/signal transducer and activator of the transcription 3 (JAK/STAT3) signaling pathway controls multiple biological processes, including cell survival, proliferation, and differentiation. Abnormally activated STAT3 signaling promotes tumor cell growth, proliferation, and survival, as well as tumor invasion, angiogenesis, and immunosuppression. Hence, JAK/STAT3 signaling has been considered a promising target for antitumor therapy. In this study, a number of ageladine A derivative compounds were synthesized. The most effective of these was found to be compound 25. Our results indicated that compound 25 had the greatest inhibitory effect on the STAT3 luciferase gene reporter. Molecular docking results showed that compound 25 could dock into the STAT3 SH2 structural domain. Western blot assays demonstrated that compound 25 selectively inhibited the phosphorylation of STAT3 on the Tyr705 residue, thereby reducing STAT3 downstream gene expression without affecting the expression of the upstream proteins, p-STAT1 and p-STAT5. Compound 25 also suppressed the proliferation and migration of A549 and DU145 cells. Finally, in vivo research revealed that 10 mg/kg of compound 25 effectively inhibited the growth of A549 xenograft tumors with persistent STAT3 activation without causing significant weight loss. These results clearly indicate that compound 25 could be a potential antitumor agent by inhibiting STAT3 activation. [ABSTRACT FROM AUTHOR]

Micelle Encapsulation Zinc‐doped copper oxide nanocomposites (MEnZn‐CuO NPs) is a novel doped metal nanomaterial prepared by our group based on Zinc doped copper oxide nanocomposites (Zn‐CuO NPs) using non‐micellar beam. Compared with Zn‐CuO NPs, MEnZn‐CuO NPs have uniform nanoproperties and high stability. In this study, we explored the anticancer effects of MEnZn‐CuO NPs on human ovarian cancer cells. In addition to affecting cell proliferation, migration, apoptosis and autophagy, MEnZn‐CuO NPs have a greater potential for clinical application by inducing HR repair defects in ovarian cancer cells in combination with poly (ADP‐ribose) polymerase inhibitors for lethal effects. [ABSTRACT FROM AUTHOR]

Abstract Micelle Encapsulation Zinc‐doped copper oxide nanocomposites (MEnZn‐CuO NPs) is a novel doped metal nanomaterial prepared by our group based on Zinc doped copper oxide nanocomposites (Zn‐CuO NPs) using non‐micellar beam. Compared with Zn‐CuO NPs, MEnZn‐CuO NPs have uniform nanoproperties and high stability. In this study, we explored the anticancer effects of MEnZn‐CuO NPs on human ovarian cancer cells. In addition to affecting cell proliferation, migration, apoptosis and autophagy, MEnZn‐CuO NPs have a greater potential for clinical application by inducing HR repair defects in ovarian cancer cells in combination with poly (ADP‐ribose) polymerase inhibitors for lethal effects.

Cancer is a fatal disease with a complex pathophysiology. Lack of specificity and cytotoxicity, as well as the multidrug resistance of traditional cancer chemotherapy, are the most common limitations that often cause treatment failure. Thus, in recent years, significant efforts have concentrated on the development of a modernistic field called nano-oncology, which provides the possibility of using nanoparticles (NPs) with the aim to detect, target, and treat cancer diseases. In comparison with conventional anticancer strategies, NPs provide a targeted approach, preventing undesirable side effects. What is more, nanoparticle-based drug delivery systems have shown good pharmacokinetics and precise targeting, as well as reduced multidrug resistance. It has been documented that, in cancer cells, NPs promote reactive oxygen species (ROS) production, induce cell cycle arrest and apoptosis, activate ER (endoplasmic reticulum) stress, modulate various signaling pathways, etc. Furthermore, their ability to inhibit tumor growth in vivo has also been documented. In this paper, we have reviewed the role of silver NPs (AgNPs) in cancer nanomedicine, discussing numerous mechanisms by which they render anticancer properties under both in vitro and in vivo conditions, as well as their potential in the diagnosis of cancer. [ABSTRACT FROM AUTHOR]

Embelin, a natural para-benzoquinone product, is derived from plants of the Embelia genus, particularly Embelia ribes Burm.f. A staple in traditional medicinal formulations for centuries, Embelin's pharmacological actions are attributed to the hydroxyl benzoquinone present in its structure. Its therapeutic potential is bolstered by unique physical and chemical properties. Recently, Embelin, recognized as a non-peptidic, cell-permeable small inhibitor of the X-linked inhibitor of apoptosis protein (XIAP), has garnered significant attention for its anticancer activity. It demonstrates various anticancer mechanisms, such as apoptosis induction, cell cycle arrest, and autophagy, in different cancer types. Additionally, Embelin modulates several signal transduction pathways, including NF-κB, PI3Kinase/AKT, and STAT3, effectively inhibiting the proliferation of diverse cancer cell lines. This literature review illuminates the anticancer potential of Embelin, detailing its mechanisms of action and prospective clinical applications, based on relevant scientific literature from the past decade sourced from various electronic databases. [ABSTRACT FROM AUTHOR]

Surgical resection was the main approach to cancer therapy, often supplemented by radiation and chemotherapy. The effectiveness of such complex treatment in many cases remains low. In this regard, there is an urgent need to search for new compounds that have selective cytotoxic activity against tumor cells and do not damage normal tissues of the organism. The review discusses mechanisms of antitumor action of cationic antimicrobial peptides (AMPs) of the cathelicidin family - human α-helical cathelicidin (LL-37), and a peptide with β-hairpin conformation – protegrin-1 (PG-1) on lung, breast, pancreas, prostate, squamous skin cancer cells, oral cancer, stomach, ovarian, colorectal cancer, melanoma, leukemia, lymphoma, glioma and neuroblastoma cells. An opportunity of antitumor and pro-oncogenic actions of the peptides and an interplay of these effects with mmunomodulatory action of AMPs on tumor-associated macrophages, natural killer cells and T-lymphocytes is discussed. Possible mechanisms of LL-37 and PG-1 selective action upon tumor cells are presented, including the interaction of LL-37 with G-protein-coupled receptors: the N formylpeptide-2 receptor (FPR2), CXC chemokine-2 (CXCR2), Mas-related gene X2 (MrgX2), purinergic (P2Y11), epidermal (EGFR/ErbB1, ERBb2), insulin-like (IGF1R) growth factors, ligand-gated ion channels (LGIC) and Tolllike (TLR) receptors, with expression varying significantly in different types of tumors, as compared to normal tissues. An increase in the level of LL-37 secretion and expression of its CAMP gene are associated with progression of lung adenocarcinoma, breast, pancreas, and prostate cancer, ovarian cancer, melanoma, and squamous cell carcinoma of the skin. In contrast, CAMP expression and LL-37 secretion are significantly reduced in gastric cancer cells, oral squamous cell cancer, colorectal cancer, leukemia, lymphomas, gliomas, and SH-SY5Y neuroblastoma. Therefore, therapeutic effects of LL-37 can only be used for specific types of tumors. The mechanisms of action of PG-1 on tumor cells are still poorly understood, although the available data indicate that protegrin exhibits a more unidirectional effect, i.e., it damages cell membranes. Protegrin-1 and LL-37 can synergistically enhance the antitumor effects of chemotherapy drugs and have a more pronounced effect on tumor cells, than upon normal cells. Natural AMPs appear to be promising candidates for the role of new antitumor agents, which are also active against malignant metastatic, recurrent multidrug-resistant tumors. On the other hand, peptides such as LL-37, in some cases, exhibit properties that can be considered pro-oncogenic, which indicates a need for further detailed studies on the molecular mechanisms of their action on tumor cells.

Background and Aim: To study the antitumor activity of 2-Methoxy-1,4-naphthoquinone (MNQ) against hepatocellular carcinoma (HCC) cells, in an attempt to fill the knowledge gap of anti-liver cancer with MNQ. Materials and Methods: Cell viability in the presence of MNQ was assessed by MTT and effect of MNQ on HepG2 cell cycle by flow cytometry. To analyze apoptosis and its molecular mechanisms, we used a combination of Hoechst 33342 staining, annexin V binding, Rhodamine 123 staining, Real-time quantitative PCR (qPCR), western blotting and confocal microscopy. On the other hand, in vivo tumor growth was measured by a xenograft tumor nude mice model. Finally, the hematoxylin and eosin staining were used to observe the pathological changes of tumor tissue. Results: The results indicate that MNQ induced apoptosis in HCC cell lines, as demonstrated by a significant increasing of mitochondrial membrane potential and G0/G1 cell cycle arrest in HepG2 cells. Furthermore, MNQ significantly up-regulated BAD and down-regulated the expression of anti-apoptotic factors NF-κB and Bcl-2 at protein and transcription levels. Finally, in vivo studies revealed that MNQ significantly inhibited tumor growth. Conclusion: MNQ suppress the proliferation and induces apoptosis of HCC cells through mitochondrial and Rel/NF-κB signal pathways. [ABSTRACT FROM AUTHOR]

Lonicerae Japonicae Flos (LJF, called Jinyinhua in China), comes from the dried flower buds or flowers to be opened of Lonicera japonica Thunb. in the Lonicera family. It has a long history of medicinal use and has a wide range of application prospects. As modern research advances, an increasing number of scientific experiments have demonstrated the anticancer potential of LJF. However, there is a notable absence of systematic reports detailing the anti-tumor effects of LJF. This review integrates the principles of Traditional Chinese Medicine (TCM) with contemporary pharmacological techniques, drawing upon literature from authoritative databases such as PubMed, CNKI, and WanFang to conduct a comprehensive study of LJF. Notably, a total of 507 compounds have been isolated and characterized from the plant to date, which include volatile oils, organic acids, flavonoids, iridoids, triterpenes and triterpenoid saponins. Pharmacological studies have demonstrated that LJF extract, along with components such as chlorogenic acid, luteolin, rutin, luteoloside, hyperoside and isochlorogenic acid, exhibits potential anticancer activities. Consequently, we have conducted a comprehensive review and summary of the mechanisms of action and clinical applications of these components. Furthermore, we have detailed the pharmacokinetics, quality control, and toxicity of LJF, while also discussing its prospective applications in the fields of biomedicine and preventive healthcare. It is hoped that these studies will provide valuable reference for the clinical research, development, and application of LJF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ma, Yuan, Jia, Zhou, Xu, Huang, Meng, Zhang and Nan.)

Cancer, the second leading cause of death worldwide following cardiovascular diseases, presents a formidable challenge in clinical settings due to the extensive toxic side effects associated with primary chemotherapy drugs employed for cancer treatment. Furthermore, the emergence of drug resistance against specific chemotherapeutic agents has further complicated the situation. Consequently, there exists an urgent imperative to investigate novel anticancer drugs. Steroidal saponins, a class of natural compounds, have demonstrated notable antitumor efficacy. Nonetheless, their translation into clinical applications has remained unrealized thus far. In light of this, we conducted a comprehensive systematic review elucidating the antitumor activity, underlying mechanisms, and inherent limitations of steroidal saponins. Additionally, we propose a series of strategic approaches and recommendations to augment the antitumor potential of steroidal saponin compounds, thereby offering prospective insights for their eventual clinical implementation. This review summarizes steroidal saponins' antitumor activity, mechanisms, and limitations. The data included in this review are sourced from authoritative databases such as PubMed, Web of Science, ScienceDirect, and others. A comprehensive summary of over 40 steroidal saponin compounds with proven antitumor activity, including their applicable tumor types and structural characteristics, has been compiled. These steroidal saponins can be primarily classified into five categories: spirostanol, isospirostanol, furostanol, steroidal alkaloids, and cholestanol. The isospirostanol and cholestanol saponins are found to have more potent antitumor activity. The primary antitumor mechanisms of these saponins include tumor cell apoptosis, autophagy induction, inhibition of tumor migration, overcoming drug resistance, and cell cycle arrest. However, steroidal saponins have limitations, such as higher cytotoxicity and lower bioavailability. Furthermore, strategies to address these drawbacks have been proposed. In summary, isospirostanol and cholestanol steroidal saponins demonstrate notable antitumor activity and different structural categories of steroidal saponins exhibit variations in their antitumor signaling pathways. However, the clinical application of steroidal saponins in cancer treatment still faces limitations, and further research and development are necessary to advance their potential in tumor therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Triptolide exhibits superior and broad-spectrum antitumor activity. However, the narrow safety window caused by the toxicity of triptolide limits its clinical applications. Although several characterized targets for triptolide are reported, the association between triptolide and its targets in cancer therapy is not fully understood. Here, we show that acute myeloid leukemia (AML) cell lines are sensitive to triptolide by constructing an in vitro cell and in vivo xenograft models. Meanwhile, the triptolide-induced hepatotoxicity increases with increasing dosages within the xenograft models. Additionally, the expression levels of WSTF-RPB1 are strongly associated with the sensitivity to triptolide in hematological cancer cells and can be downregulated in a dose and time-dependent manner. Finally, we show that optimizing dosing regimens can achieve the same pharmaceutical effect and reduce toxicity. In summary, this study aims to search for triptolide-sensitive cell lines as well as the underlying molecular mechanisms in order to broaden the safety window of triptolide; thus, increasing its clinical utility. [ABSTRACT FROM AUTHOR]

Triptolide exhibits superior and broad-spectrum antitumor activity. However, the narrow safety window caused by the toxicity of triptolide limits its clinical applications. Although several characterized targets for triptolide are reported, the association between triptolide and its targets in cancer therapy is not fully understood. Here, we show that acute myeloid leukemia (AML) cell lines are sensitive to triptolide by constructing an in vitro cell and in vivo xenograft models. Meanwhile, the triptolide-induced hepatotoxicity increases with increasing dosages within the xenograft models. Additionally, the expression levels of WSTF-RPB1 are strongly associated with the sensitivity to triptolide in hematological cancer cells and can be downregulated in a dose and time-dependent manner. Finally, we show that optimizing dosing regimens can achieve the same pharmaceutical effect and reduce toxicity. In summary, this study aims to search for triptolide-sensitive cell lines as well as the underlying molecular mechanisms in order to broaden the safety window of triptolide; thus, increasing its clinical utility.

Cancer is a fatal disease with a complex pathophysiology. Lack of specificity and cytotoxicity, as well as the multidrug resistance of traditional cancer chemotherapy, are the most common limitations that often cause treatment failure. Thus, in recent years, significant efforts have concentrated on the development of a modernistic field called nano-oncology, which provides the possibility of using nanoparticles (NPs) with the aim to detect, target, and treat cancer diseases. In comparison with conventional anticancer strategies, NPs provide a targeted approach, preventing undesirable side effects. What is more, nanoparticle-based drug delivery systems have shown good pharmacokinetics and precise targeting, as well as reduced multidrug resistance. It has been documented that, in cancer cells, NPs promote reactive oxygen species (ROS) production, induce cell cycle arrest and apoptosis, activate ER (endoplasmic reticulum) stress, modulate various signaling pathways, etc. Furthermore, their ability to inhibit tumor growth in vivo has also been documented. In this paper, we have reviewed the role of silver NPs (AgNPs) in cancer nanomedicine, discussing numerous mechanisms by which they render anticancer properties under both in vitro and in vivo conditions, as well as their potential in the diagnosis of cancer.

The incidence of common gynecological malignancies remains high, with current treatments facing multiple limitations and adverse effects. Thus, continuing the search for safe and effective oncologic treatment strategies continues. Resveratrol (RES), a natural non-flavonoid polyphenolic compound, is widely found in various plants and fruits, such as grapes, Reynoutria japonica Houtt., peanuts, and berries. RES possesses diverse biological properties, including neuroprotective, antitumor, anti-inflammatory, and osteoporosis inhibition effects. Notably, RES is broadly applicable in antitumor therapy, particularly for treating gynecological tumors (cervical, endometrial, and ovarian carcinomas). RES exerts antitumor effects by promoting tumor cell apoptosis, inhibiting cell proliferation, invasion, and metastasis, regulating tumor cell autophagy, and enhancing the efficacy of antitumor drugs while minimizing their toxic side effects. However, comprehensive reviews on the role of RES in combating gynecological tumors and its mechanisms of action are lacking. This review aims to fill this gap by examining the RES antitumor mechanisms of action in gynecological tumors, providing valuable insights for clinical treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Meng, Zhang and Wang.)

The burgeoning field of starch-based nanomaterials in biomedical applications has perceived notable progressions, with a particular emphasis on their pivotal role in precision drug delivery and the inhibition of tumor growth. The complicated challenges in current biomedical research require innovative approaches for improved therapeutic outcomes, prompting an exploration into the possible of starch-based nanomaterials. The conceptualization of this review emerged from recognizing the need for a comprehensive examination of the structural attributes, versatile properties, and mechanisms underlying the efficiency of starch-based nanomaterials in inhibiting tumor growth and enabling targeted drug delivery. This review delineates the substantial growth in utilizing starch-based nanomaterials, elucidating their small size, high surface-volume ratio, and biocompatibility, predominantly emphasizing their possible to actively recognize cancer cells, deliver anticancer drugs, and combat tumors efficiently. The investigation of these nanomaterials encompasses to improving biocompatibility and targeting specific tissues, thereby contributing to the evolving landscape of precision medicine. The review accomplishes by highlighting the auspicious strategies and modern developments in the field, envisioning a future where starch-based nanomaterials play a transformative role in molecular nanomaterials, evolving biomedical sciences. The translation of these advancements into clinical applications holds the potential to revolutionize targeted drug delivery and expand therapeutic outcomes in the realm of precision medicine. [ABSTRACT FROM AUTHOR]

Fish oil (FO) and selenium (Se) possess antiangiogenic potential in malignant tumors. This study aimed to determine whether combination of FO and Se enhanced treatment efficacy of low-dose antiangiogenic agent Avastin (bevacizumab) in a dose-dependent manner and targeted multiple signaling pathways in triple-negative breast cancer (TNBC)-bearing mice. Randomized into five groups, mice received treatment with either physiological saline (control), Avastin alone, or Avastin in combination with low, medium, and high doses of FO/Se. The target signaling molecules for anticancer were determined either by measuring protein or mRNA expression. Avastin-treated mice receiving FO/Se showed lower tumor growth and metastasis than did mice treated with Avastin alone. Combination-treated mice exhibited lower expressions in multiple proangiogenic (growth) factors and their membrane receptors, and altered cytoplasmic signaling molecules (PI3K-PTEN-AKT-TSC-mTOR-p70S6K-4EBP1, Ras-Raf-MEK-ERK, c-Src-JAK2-STAT3-TMEPAI-Smad, LKB1-AMPK, and GSK3β/β-catenin). Dose-dependent inhibition of down-stream targets including epithelial-to-mesenchymal transition transcription factors, nuclear cyclin and cyclin-dependent kinases, cancer stem cell markers, heat shock protein (HSP-90), hypoxia-inducible factors (HIF-1α/-2α), matrix metalloprotease (MMP-9), and increased apoptosis were observed. These results suggest that combination treatment with FO and Se increases the therapeutic efficacy of Avastin against TNBC in a dose-dependent manner through multiple signaling pathways in membrane, cytoplasmic, and nucleic targets.

Trained immunity refers to the innate immune system building memory-like features in response to subsequent infections and vaccinations. Compared with classical tumor vaccines, trained immunity-related vaccines (TIrV) are independent of tumor-specific antigens. Bacterial outer membrane vesicles (OMVs) contain an abundance of PAMPs and have the potential to act as TIrV-inducer, but face challenges in endotoxin tolerance, systemic delivery, long-term training, and trained tumor-associated macrophage (TAM)-mediated antitumor phagocytosis. Here, an OMV-based TIrV is developed, OMV nanohybrids (OMV-SIRPα@CaP/GM-CSF) for exerting vaccine-enhanced antitumor activity. In the bone marrow, GM-CSF-assisted OMVs train bone marrow progenitor cells and monocytes, which are inherited by TAMs. In tumor tissues, SIRPα-Fc-assisted OMVs trigger TAM-mediated phagocytosis. This TIrV can be identified by metabolic and epigenetic rewiring using transposase-accessible chromatin (ATAC) and transcriptome sequencing. Furthermore, it is found that the TIrV-mediated antitumor mechanism in the MC38 tumor model (TAM-hot and T cell-cold) is trained immunity and activated T cell response, whereas in the B16-F10 tumor model (T cell-hot and TAM-cold) is primarily mediated by trained immunity. This study not only develops and identifies OMV-based TIrV, but also investigates the trained immunity signatures and therapeutic mechanisms, providing a basis for further vaccination strategies., (© 2023 Wiley-VCH GmbH.)

With advances in cancer biology and an ever-deepening understanding of molecular virology, oncolytic virus (OV)-driven therapies have developed rapidly and become a promising alternative to traditional cancer therapies. In recent years, satisfactory results for oncolytic virus therapy (OVT) are achieved at both the cellular and organismal levels, and efforts are being increasingly directed toward clinical trials. Unfortunately, OVT remains ineffective in these trials, especially when performed using only a single OV reagent. In contrast, integrated approaches, such as using immunotherapy, chemotherapy, or radiotherapy, alongside OVT have demonstrated considerable efficacy. The challenges of OVT in clinical efficacy include the restricted scope of intratumoral injections and poor targeting of intravenous administration. Further optimization of OVT delivery is needed before OVs become a viable therapy for tumor treatment. In this review, the development process and antitumor mechanisms of OVs are introduced. The advances in OVT delivery routes to provide perspectives and directions for the improvement of OVT delivery are highlighted. This review also discusses the advantages and limitations of OVT monotherapy and combination therapy through the lens of recent clinical trials and aims to chart a course toward safer and more effective OVT strategies., (© 2023 Wiley-VCH GmbH.)

Fish oil (FO) and selenium (Se) possess antiangiogenic potential in malignant tumors. This study aimed to determine whether combination of FO and Se enhanced treatment efficacy of low-dose antiangiogenic agent Avastin (bevacizumab) in a dose-dependent manner and targeted multiple signaling pathways in triple-negative breast cancer (TNBC)-bearing mice. Randomized into five groups, mice received treatment with either physiological saline (control), Avastin alone, or Avastin in combination with low, medium, and high doses of FO/Se. The target signaling molecules for anticancer were determined either by measuring protein or mRNA expression. Avastin-treated mice receiving FO/Se showed lower tumor growth and metastasis than did mice treated with Avastin alone. Combination-treated mice exhibited lower expressions in multiple proangiogenic (growth) factors and their membrane receptors, and altered cytoplasmic signaling molecules (PI3K-PTEN-AKT-TSC-mTOR-p70S6K-4EBP1, Ras-Raf-MEK-ERK, c-Src-JAK2-STAT3-TMEPAI-Smad, LKB1-AMPK, and GSK3β/β-catenin). Dose-dependent inhibition of down-stream targets including epithelial-to-mesenchymal transition transcription factors, nuclear cyclin and cyclin-dependent kinases, cancer stem cell markers, heat shock protein (HSP-90), hypoxia-inducible factors (HIF-1α/-2α), matrix metalloprotease (MMP-9), and increased apoptosis were observed. These results suggest that combination treatment with FO and Se increases the therapeutic efficacy of Avastin against TNBC in a dose-dependent manner through multiple signaling pathways in membrane, cytoplasmic, and nucleic targets. [ABSTRACT FROM AUTHOR]

DNA nanostructure-based drug delivery system (DDS) has become an advanced therapeutic strategy for cancer because of its unsurpassed editability, intrinsic biodegradability, and tunable multifunctionality. An intelligent DNA nanosystem integrating targeting, immunostimulation, and chemotherapy was constructed based on unmethylated cytosine-phosphate-guanine oligonucleotides (CpG ODNs) DNA nanohydrogels (CpG-MUC1-hydrogel). By facile one-step self-assembly, the cross-shaped DNAs (C-DNAs) assembled from pH-responsive I-motif sequences and targeted MUC1 aptamer-immunoadjuvant CpG-fused sequences (CpG-MUC1) were integrated into DNA nanohydrogels with controllable size by the hybridization of DNA linkers. Subsequently, DOX was successively intercalated into the base pairs of CpG-MUC1-hydrogel, resulting in CpG-MUC1-hydrogel/Dox that would disassemble and release DOX and CpGs at acidic conditions. After MUC1-mediated internalization, CpG-MUC1-hydrogel/Dox dissociated in the endo/lysosomes and induced favorable apoptosis of tumor cells. Afterward, liberated CpGs triggered vast cytokine secretion from immune cells which elicited potent immune response against malignancy. Notably, CpG-MUC1-hydrogel induced an apoptosis effect on MCF-7 cells via significantly increasing the Bax/Bcl 2 ratios and a higher level of tumor necrosis factor (TNF-α) on RAW264.7 cells than naked CpGs. Our results demonstrated that self-assembled CpG-MUC1-hydrogel represented an attractive DDS for precise delivery, potent immunostimulating activity, and considerable combination efficiency with few adverse effects, which is expected to make breakthroughs in clinical translation.

At present, the polysaccharide antitumor research is focused on how to further improve the antitumor activity of polysaccharides. The structural modification of polysaccharides can enhance their antitumor activity to a certain extent. The antitumor mechanisms of polysaccharide derivatives mainly contain the inducing apoptosis of tumor cells, effecting on the cycle of tumor cells, enhancing the antioxidant activity of organism, activating the body's immune response and inhibiting the tumor angiogenesis. Herein, the common methods of polysaccharide modification, such as sulfation, carboxymethylation, phosphorylation and acetylation, were summarized. At the same time, the effects of chemical modification of polysaccharides on their antitumor mechanisms and activity were analyzed and discussed.

Zinc-doped copper oxide nanocomposites (nZn-CuO NPs) are novel nanparticles synthesized by our group. In the present study, the antitumor effects and the underlying molecular mechanisms of the nZn-CuO NPs were investigated. The cytotoxicity of nZn-CuO NPs against several types of cancer cell lines was studied using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS)/phenazinemethosulfate (PMS) assay. Results showed that nZn-CuO NPs exerted obvious antiproliferation effects on cancer cells and relatively weak antiproliferation effects on normal cells. The antitumor mechanisms of nZn-CuO NPs were further investigated using human liver cancer HepG2 cells and human pancreatic cancer Panc28 cells. Hoechst 33342 staining and FITC-Annexin V/PI staining showed that nZn-CuO NPs could induce cell apoptosis in a dose dependent manner. Cell-cycle analysis using flow cytometry revealed that nZn-CuO NPs were able to arrest the cell cycle in the G2/M phase. Also, nZn-CuO NPs were found to induce reactive oxygen species (ROS) generation. Further studies confirmed that nZn-CuO NPs could increase p-IKKα/β and nucleus p-NF-κB p65 expressions and decrease IKKα, IKKβ, IκBα, and nucleus NF-κB p65 expressions in both cell lines. Overall, our data demonstrated that nZn-CuO NPs could selectively inhibit the growth of cancer cells via ROS-mediated NF-κB activation. The current study provides primary evidence that nZn-CuO NPs possess the potential to be developed as a novel anticancer agent.