- Home
- A-Z Publications
- Current Cancer Drug Targets
- Previous Issues
- Volume 22, Issue 5, 2022
Current Cancer Drug Targets - Volume 22, Issue 5, 2022
Volume 22, Issue 5, 2022
-
-
The Interactions among Hypertension, Cancer, and COVID-19: Perspective with Regard to Ca2+/cAMP Signalling
More LessBackground: The hypothesis that hypertension is clinically associated with an enhanced risk of developing cancer has been highlighted. However, the working principles involved in this link are still under intensive discussion. A correlation among inflammation, hypertension, and cancer could accurately describe the clinical link between these diseases. In addition, dyshomeostasis of Ca2+ has been considered to be involved in both cancer and hypertension, and inflammation. There is a strong link between Ca2+ signalling, e.g. enhanced Ca2+ signals, and inflammatory outcomes. cAMP also modulates pro- and anti-inflammatory outcomes; pharmaceuticals, which increase intracellular cAMP levels, can decrease the production of proinflammatory mediators and enhance the production of antiinflammatory outcomes. Objective: This article highlights the participation of Ca2+/cAMP signalling in the clinical association among inflammation, hypertension, and an enhanced risk for the development of cancer. In addition, considering that research on coronavirus disease 2019 (COVID-19) is a rapidly evolving field, this article also reviews recent reports related to the role of Ca2+ channel blockers in restoring Ca2+ signalling disruption due to COVID-19, including the relationship among COVID-19, cancer, and hypertension. Conclusion: An understanding of the association among these diseases could expand current pharmacotherapy, involving Ca2+ channel blockers and pharmaceuticals that facilitate a rise in cAMP levels.
-
-
-
Nanocarrier System for Increasing the Therapeutic Efficacy of Oxaliplatin
Authors: Negin Alavi, Majid Rezaei, Parvaneh Maghami, Azar Fanipakdel and Amir AvanThe application of Oxaliplatin (OxPt) in different malignancies is reported to be accompanied by several side effects, including neuropathy, nausea, vomiting, diarrhea, mouth sores, low blood counts, loss of appetite, etc. The passive or active targeting of different tumors can improve OxPt delivery. Considering the demand for novel systems meant to improve the OxPt efficacy and define the shortcomings, we provided an overview of different approaches regarding the delivery of OxPt. There is an extending body of data that exhibits the value of liposomes and polymer- based drug delivery systems as the most successful systems among the OxPt drug delivery procedures. Several clinical trials have been carried out to investigate the side effects and dose-limiting toxicity of liposomal oxaliplatin, such as the assessment on Safety Study of MBP-426 (Liposomal Oxaliplatin Suspension for Injection) to Treat Advanced or Metastatic Solid Tumors. In addition, several studies indicated the biocompatibility and biodegradability of this product, as well as its option for being fictionalized to derive specialized smart nanosystems for the treatment of cancer. The better delivery of OxPt with weaker side effects could be generated by the exertion of Oxaliplatin, which involves the aggregation of new particles and multifaceted nanocarriers to compose a nanocomposite with both inorganic and organic nanoparticles.
-
-
-
Modifications of Ribonucleases in Order to Enhance Cytotoxicity in Anticancer Therapy
Authors: Mohammadreza Nassiri, Vinod Gopalan and Masoume Vakili-AzghandiRibonucleases (RNases) are a superfamily of enzymes that have been extensively studied since the 1960s. For a long time, this group of secretory enzymes was studied as an important model for protein chemistry such as folding, stability, and enzymatic catalysis. Since it was discovered that RNases displayed cytotoxic activity against several types of malignant cells, recent investigation has focused mainly on the biological functions and medical applications of engineered RNases. In this review, we describe the structures, functions, and mechanisms of antitumor activity of RNases. They operate at the crossroads of transcription and translation, preferentially degrading tRNA. As a result, this inhibits protein synthesis, induces apoptosis, and causes the death of cancer cells. This effect can be enhanced thousands of times when RNases are conjugated with monoclonal antibodies. Such combinations, called immunoRNases, have demonstrated selective antitumor activity against cancer cells both in vitro and in animal models. This review summarizes the current status of engineered RNases and immunoRNases as promising novel therapeutic agents for different types of cancer. Also, we describe our experimental results from published or previously unpublished research and compare them with other scientific information.
-
-
-
The Potential of Natural Products in the Treatment of Triple-negative Breast Cancer
Authors: Danny Y. J. Ke, Sara El-Sahli and Lisheng WangTriple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks receptors for targeted therapy. Consequently, chemotherapy is currently the mainstay of systemic treatment options. However, the enrichment of cancer stem cells (CSC, a subpopulation with stem-cell characteristics and tumor-initiating propensity) promotes chemo-resistance and tumorigenesis, resulting in cancer recurrence and relapse. Furthermore, toxic side effects of chemotherapeutics reduce patient wellbeing. Natural products specifically compounds derived from plants, have the potential to treat TNBC and target CSCs by inhibiting CSC signaling pathways. Literature evidence from six promising compounds was reviewed, including sulforaphane, curcumin, genistein, resveratrol, lycopene, and epigallocatechin-3-gallate. These compounds have been shown to promote cell cycle arrest and apoptosis in TNBC cells. They also could inhibit the epithelial-mesenchymal transition (EMT) that plays an important role in metastasis. In addition, those natural compounds have been found to inhibit pathways important for CSCs, such as NF-ΚB, PI3K/Akt/mTOR, Notch 1, Wnt/β- catenin, and YAP. Clinical trials conducted on these compounds have shown varying degrees of effectiveness. Epidemiological case-control studies for the compounds commonly consumed in certain human populations have also been summarized. While in vivo and in vitro data are promising, further basic and clinical investigations are required. Likely, natural products in combination with other drugs may hold great potential to improve TNBC treatment efficacy and patient outcomes.
-
-
-
Novel Compound, ND-17, Regulates the JAK/STAT, PI3K/AKT, and MAPK Pathways and Restrains Human T-lymphoid Leukemia Development
Authors: Weina Ma, Yanhong Liu, Panpan Lei, Man Zhu and Xiaoyan PanBackground: T cell acute lymphoblastic leukemia (T-ALL) is an invasive hematological malignant disorder of T cell progenitors. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway plays an important role in the development of T-ALL and in the inhibition of the key molecule, JAK2, and could suppress T-ALL cell proliferation. Objective: The objective of this study was to investigate the in vitro anti-tumor effects of a novel nilotinib derivative, ND-17, on cancer cell lines via its interactions with JAK2. Methods: The effects of ND-17 on cell proliferation and on cell cycle and apoptosis were evaluated using the tetrazolium assay and flow cytometry, respectively. In addition, the ND-17/JAK2 binding interactions were evaluated using surface plasmon resonance and western blot analyses. Results: ND-17 exerted the greatest inhibitory effects on T-ALL cells amongst all hematological cancer cell lines tested. Flow cytometric analysis indicated that ND-17 blocked the cell cycle at the S phase in T-ALL cells. Nilotinib did not significantly inhibit T-ALL cell growth or regulate the cell cycle. Preliminary investigations revealed that the regulation of cyclin-dependent kinases/cyclins was attributed to ND-17-induced cell cycle arrest. Furthermore, ND-17 could bind to JAK2 with strong affinity, and more importantly, ND-17 bound to the ATP pocket of JAK2 in a manner similar to the potent inhibitor. Thus, ND-17 treatment exhibited a prominent effect in inhibiting the phosphorylation of JAK2 in T-ALL cells. An increase in the phosphorylation of JAK2 was observed in interleukin-6- stimulated Jurkat cells, which was reversed by ND-17 treatment. Meanwhile, the combination of TG- 101348 and ND-17 led to further improvement in inhibiting the phosphorylation of JAK2. Moreover, the transfection and knockdown of JAK2 altered the inhibitory effect of ND-17 on Jurkat cell viability. In addition, ND-17 treatment suppressed the JAK/STAT, phosphatidylinositol-3-kinase/protein kinase B/mechanistic target of rapamycin, and mitogen-activated protein kinase/extracellular signal-regulated protein kinases 1 and 2 signaling pathways. Conclusion: These findings suggest that ND-17 could be a promising JAK2 inhibitor for the treatment of T-ALL.
-
-
-
Increase in Cisplatin Resistance by MeCP2 in Human Gastric Cancer through the Activation of the AKT Pathway by Facilitating PDK-1 Transcription
Authors: Bo Guo, Shuang Cai, Wen Li, Chen Guo, Yijie Liu, Xiaoping Ma, Hailin Ma and Lingyu ZhaoBackground: Increasing evidence indicates that an imbalance in oncogenes is implicated in cancer chemotherapy resistance. Methyl-CpG binding protein 2 (MeCP2), which acts as a major epigenetic regulator of the expression of various genes, is involved in the carcinogenesis and progression of gastric cancer. However, is it not known whether the role of MeCP2 is vital in acquired cisplatin resistance in gastric cancer. Objective: This study aimed to determine whether inhibition of MeCP2 expression could sensitize DDP-resistant GC cells to DDP and elucidate the underlying molecular mechanism. Methods: qRT-PCR and western blotting were used to evaluate MeCP2 expression in DDP-resistant GC cells. Subsequently, cell viability, colony formation, cell cycle, apoptosis, and tumorigenicity assays were performed to explore the in vitro and in vivo roles of MeCP2. Chromatin immunoprecipitation- qPCR and luciferase reporter assays were used to identify whether 3-phosphoinositide-dependent protein kinase 1 (PDK-1) was a direct target gene of MeCP2. Results: MeCP2 was upregulated in malignant DDP-resistant cells compared to non-DDP-resistant GC cells or normal gastric epithelial cells. MeCP2 knockdown increased the sensitivity of DDP-resistant GC cells to DDP, resulting in reduced cell growth, G0/G1 phase arrest, and increased apoptosis, whereas MeCP2 overexpression attenuated DDP sensitivity of DDP-resistant GC cells. In addition, MeCP2 knockdown enhanced DDP sensitivity in vivo. MeCP2 elevated PDK-1 expression by binding to CpG sites in promoter regions, and inhibition of PDK-1 reversed the inductive effect of MeCP2 overexpression on DDP resistance in GC cells. Conclusion: These findings indicate that silencing of MeCP2 may potentiate DDP-induced cell death, thereby providing a promising therapeutic strategy for GC.
-
-
-
Polyphyllin VII is a Potential Drug Targeting CD44 Positive Colon Cancer Cells
More LessBackground: Current therapies for colon cancer are hindered by treatment failure and recurrence, mainly due to colon cancer stem cells (CSCs). Thus, treatment using drugs targeting CSCs should be effective in eliminating colon cancer cells and impeding cancer recurrence. Objective: This study aimed to test if PPVII can be a potent drug candidate for the treatment of colon cancer by targeting CD44 positive colon cancer cells. Methods: In this study, we first demonstrated that CD44 is highly expressed in colon cancer tissues by TCGA/GTEX database analysis and immunohistochemical staining. Results: In this study, we first demonstrated that CD44 is highly expressed in colon cancer tissues by TCGA/GTEX database analysis. CD44 had high accuracy as a diagnostic and predictive index for colorectal cancer through receiver operating characteristic curve (ROC) analysis. At the same time, survival curve analysis also showed that the high expression of CD44 was associated with poor prognosis in patients with colon cancer. CD44’s higher expression in colon cancer tissues was further confirmed by immunohistochemical staining; the positive rate of CD44 expression was 87.95%. Then, one of the constituents that derives from the root of Paris polyphylla, Polyphyllin VII (PPVII), has been confirmed to inhibit the migration of colon cancer cells. Our results also demonstrated that PPVII could inhibit the sphere-forming ability of colon cancer cells. Further experiment results showed that PPVII could downregulate the expression of CD44 in colon cancer cells. In addition, PPVII was proved to have inhibitory effects against CD44 positive colon cancer cells. Conclusion: Therefore, PPVII might be a potent candidate reagent for the treatment of colon cancer by targeting CD44 positive colon cancer cells.
-
Volumes & issues
-
Volume 24 (2024)
-
Volume 23 (2023)
-
Volume 22 (2022)
-
Volume 21 (2021)
-
Volume 20 (2020)
-
Volume 19 (2019)
-
Volume 18 (2018)
-
Volume 17 (2017)
-
Volume 16 (2016)
-
Volume 15 (2015)
-
Volume 14 (2014)
-
Volume 13 (2013)
-
Volume 12 (2012)
-
Volume 11 (2011)
-
Volume 10 (2010)
-
Volume 9 (2009)
-
Volume 8 (2008)
-
Volume 7 (2007)
-
Volume 6 (2006)
-
Volume 5 (2005)
-
Volume 4 (2004)
-
Volume 3 (2003)
-
Volume 2 (2002)
-
Volume 1 (2001)