Novel Approach For Cancer Therapy Research Articles

Critical roles and clinical perspectives of RNA methylation in cancer.

RNA modification, especially RNA methylation, is a critical posttranscriptional process influencing cellular functions and disease progression, accounting for over 60% of all RNA modifications. It plays a significant role in RNA metabolism, affecting RNA processing, stability, and translation, thereby modulating gene expression and cell functions essential for proliferation, survival, and metastasis. Increasing studies have revealed the disruption in RNA metabolism mediated by RNA methylation has been implicated in various aspects of cancer progression, particularly in metabolic reprogramming and immunity. This disruption of RNA methylation has profound implications for tumor growth, metastasis, and therapy response. Herein, we elucidate the fundamental characteristics of RNA methylation and their impact on RNA metabolism and gene expression. We highlight the intricate relationship between RNA methylation, cancer metabolic reprogramming, and immunity, using the well-characterized phenomenon of cancer metabolic reprogramming as a framework to discuss RNA methylation's specific roles and mechanisms in cancer progression. Furthermore, we explore the potential of targeting RNA methylation regulators as a novel approach for cancer therapy. By underscoring the complex mechanisms by which RNA methylation contributes to cancer progression, this review provides a foundation for developing new prognostic markers and therapeutic strategies aimed at modulating RNA methylation in cancer treatment.

Recent Developments in Combination Chemotherapy for Colorectal and Breast Cancers with Topoisomerase Inhibitors.

DNA topoisomerases are important enzymes that stabilize DNA supercoiling and resolve entanglements. There are two main types of topoisomerases in all cells: type I, which causes single-stranded DNA breaks, and type II, which cuts double-stranded DNA. Topoisomerase activity is particularly increased in rapidly dividing cells, such as cancer cells. Topoisomerase inhibitors have been an effective chemotherapeutic option for the treatment of several cancers. In addition, combination cancer therapy with topoisomerase inhibitors may increase therapeutic efficacy and decrease resistance or side effects. Topoisomerase inhibitors are currently being used worldwide, including in the United States, and clinical trials on the combination of topoisomerase inhibitors with other drugs are currently underway. The primary objective of this review was to comprehensively analyze the current clinical landscape concerning the combined application of irinotecan, an extensively investigated type I topoisomerase inhibitor for colorectal cancer, and doxorubicin, an extensively researched type II topoisomerase inhibitor for breast cancer, while presenting a novel approach for cancer therapy.

Abstract CT170: Initial safety and feasibility results from a first-in-human clinical trial evaluating a novel magnetic hyperthermia approach for the treatment of metastatic solid tumors

Abstract A novel approach for cancer therapy was developed, comprising of magnetic multicore iron oxide nanoparticles (SaNPs) and alternating magnetic field (AMF) application. SaNPs are administered IV to the patient and accumulate in tumors through the enhanced permeability and retention (EPR) effect. The patient then undergoes regional AMF application (300kHz) that is converted to thermal energy, inducing sub-ablative hyperthermic cancer cell death. Based on extensive pre-clinical testing, treatment was proven safe and biocompatible in animal models without any associated toxicities. Efficacy studies in a murine metastatic cancer model, demonstrated the ability to reduce the number and size of metastatic lesions. Methods: A First-in-Human open label dose escalation study was designed to evaluate the feasibility and safety of treatment in patients (n=18) with advanced metastatic solid tumors. A secondary objective was to evaluate initial efficacy signs. Eligibility criteria included patients with a life expectancy of at least 30 days with measurable disease according to RECIST 1.1. The patients underwent toxicity analysis and MRI scans without contrast media before (baseline), after treatment, and at the end of the follow-up period of 1 month. Vital signs were monitored before, during, and after treatment. Measurements included ECG, oral and body surface temperatures, blood pressure, heart rate, and oxygen saturation. Results: 3 patients were enrolled in the first cohort that received a single SaNP injection of 10% (first dose level) without AMF. No systemic toxicity was observed. 7 patients were then enrolled and SaNP was administered at the same dose followed by AMF irradiation (first dose level of 40%) of the torso area, conducted for two intervals of 5 min. each. SaNP administration procedures were successful in all cases whereas, 3 patients succeeded to complete the full treatment in accordance to the study protocol. During AMF exposure, the patients were covered with a cooling blanket and temperatures were monitored using fiber-optic sensors. There were no significant temperature deviations beside one patient, where a rise in oral temperature was noted due to the presence of dental implants which heated up. In all patients there were no significant differences in any of the vital signs post-injection nor before or after AMF except for one patient, for whom increased heart rate was observed during irradiation, returning to baseline thereafter. No treatment-related abnormal clinical pathology or urinalysis results were identified. Some fluctuations were observed, attributed to the disease stage. Although tumor response was not expected at the first dose levels, MRI and CT results for one patient showed a reduction in a breast tumor and in another patient, stable disease was reported. Conclusion: SaNP administration either alone or followed by AMF application was not associated with any significant adverse reactions, and no clinical or humoral toxicity was observed at initial doses of 10% SaNP and 40% AMF. Citation Format: Sarah Kraus, Cheri Tal, Boaz Shalev, Moshe Eltanani, Pazit Rukenstein, Shir Arbib, Michal Eck, Raz Khandadash, Shaul Atar, Arnoldo Cyjon, Ofer Shalev. Initial safety and feasibility results from a first-in-human clinical trial evaluating a novel magnetic hyperthermia approach for the treatment of metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT170.

GSH-specific fluorescent probe for sensing, bioimaging, rapid screening of natural inhibitor Celastrol and ccRCC theranostics.

High level of intracellular glutathione (GSH) has been identified as a major barrier for cancer therapy. Therefore, effective regulation of GSH can be regarded as a novel approach for cancer therapy. In this study, an off-on fluorescent probe (NBD-P) is developed for selective and sensitive sensing GSH. NBD-P has a good cell membrane permeability that can be applied in bioimaging endogenous GSH in living cells. Moreover, the NBD-P probe is used to visualize GSH in animal models. In addition, a rapid drug screening method is successfully established using the fluorescent probe NBD-P. A potent natural inhibitor of GSH is identified as Celastrol from Tripterygium wilfordii Hook F, which effectively triggers mitochondrial apoptosis in clear cell renal cell carcinoma (ccRCC). More importantly, NBD-P can selectively respond to GSH fluctuations to distinguish cancer tissues from normal tissues. Thus, the present study provides insights into fluorescence probes for the screening GSH inhibitors and cancer diagnosis, as well as in-depth exploration of the anti-cancer effects of Traditional Chinese Medicine (TCM).

Extrachromosomal Circular DNAs, Amplified Oncogenes, and CRISPR-Cas9 System.

Structurally rearranged extrachromosomal circular DNAs (eccDNAs) have been identified in tumor cells, many of which carry regions related to recurrent cancer driver oncogenes (e.g., CCND1, EGFR, and MYC). In a tumor cell, eccDNAs are carrying regions associated with oncogene amplification (>10-fold amplified-copy numbers in human tumors) and poor outcome across multiple cancers. Even though dual-delivery of pairs of CRISPR and CRISPR-associated protein 9 (Cas9) guiding RNAs into normal human cells was reported to induce circularization of genes and chromosomes, in bacteria, the CRISPR-Cas9 system primarily targets extrachromosomal rearranged elements. Likewise, in cancer cells, it is expected that a designed CRISPR-Cas9 system would be able to target extrachromosomal copy number amplifications and produce double strand breaks detrimental to cellular fitness by dictating gene-independent copy number loss-of-fitness effects and antiproliferative responses. A system designed against amplified amplicons may provide a novel approach for cancer therapy and propose a practical implication for CRISPR-Cas9 pairs as a pathway in therapeutic strategies of cancer. SIGNIFICANCE STATEMENT: Structurally rearranged extrachromosomal circular DNAs (eccDNAs) have been identified in tumor cells. Many eccDNAs are carrying regions related to recurrent cancer driver oncogenes (e.g. CCND1, EGFR and MYC). It is expected that a designed CRISPR-Cas9 system would able to target extrachromosomal recurrent oncogenes.

The F1Fo-ATPase inhibitor protein IF1 in pathophysiology.

The endogenous inhibitor of ATP synthase is a protein of about 10 kDa, known as IF1 which binds to the catalytic domain of the enzyme during ATP hydrolysis. The main role of IF1 consists of limiting ATP dissipation under condition of severe oxygen deprivation or in the presence of dysfunctions of mitochondrial respiratory complexes, causing a collapse in mitochondrial membrane potential and therefore ATP hydrolysis. New roles of IF1 are emerging in the fields of cancer and neurodegeneration. Its high expression levels in tumor tissues have been associated with different roles favouring tumor formation, progression and evasion. Since discordant mechanisms of action have been proposed for IF1 in tumors, it is of the utmost importance to clarify them in the prospective of defining novel approaches for cancer therapy. Other IF1 functions, including its involvement in mitophagy, may be protective for neurodegenerative and aging-related diseases. In the present review we aim to clarify and discuss the emerging mechanisms in which IF1 is involved, providing a critical view of the discordant findings in the literature.

Fasting Techniques – A Novel Approach for Cancer Therapy with Cyclophosphamide Loaded Nanoparticles on DAL-Mice

Fasting Techniques – A Novel Approach for Cancer Therapy with Cyclophosphamide Loaded Nanoparticles on DAL-Mice

A Drug‐Free Therapeutic System for Cancer Therapy by Diselenide‐Based Polymers Themselves

The application of nanotechnology-based drug delivery systems has resulted in great progresses in cancer therapy. However, current systems ultimately depend on the action of the drug itself and almost all nanocarriers only serve as excipients without any therapeutic efficacy. Herein, a drug-free therapeutic system is put forward, in which synthetic polymers themselves naturally exhibit effective anticancer activity without the loading of additional chemotherapy drugs. Aiming at this goal, amphiphilic poly(diselenide-carbonate) copolymers (PSeSeTMC), consisting of monomethyl ether poly(ethylene glycol) and diselenide-based polycarbonates, are designed and synthesized to build spherical nanoparticles, which show effective and broad-spectrum anticancer activities against multiple cancer cell lines and high selectivity toward cancer cells. Moreover, the anticancer activities can be well controlled by tuning the selenium contents in polymers. Mechanistic investigations indicate that PSeSeTMC can selectively induce cancer cells to express excessive reactive oxygen species, thereby leading to significant cellular apoptosis. In vivo antitumor studies further demonstrate high therapeutic efficacy and low side effects on normal tissue. Overall, this work provides a novel approach for cancer therapy by utilizing carriers themselves. Considering the fabrication process is pretty simple, this diselenide-based polymeric system has great potential in clinical translation.

Green Synthesis, Experimental and Theoretical Studies to Discover Novel Binders of Exosomal Tetraspanin CD81 Protein.

A new class of benzothiazole-appended quinoline derivatives (6–8) was synthesized via one-pot TPGS micellar-mediated acid-catalyzed nucleophilic addition, followed by aerobic oxidative cyclization of 3-formylquinoline-2-one (2), 3-formylquinoline-2-thione (3), and 2-azidoquinoline-3-carbaldehyde (4) individually with 2-amino thiophenol (5). The structures of the prepared compounds were confirmed using suitable spectroscopic methods complemented with single-crystal X-ray diffraction analysis. Time-dependent density functional theory-based optimization of molecular structures, bond lengths, bond angles, HOMO–LUMO energy gaps, and molecular electrostatic potential maps was theoretically computed at the B3LYP/6-311++g(d) level. The molecular docking studies recommended that 6–8 bound to the active site cavity of CD81 effectively with the binding energies of −6.9, −6.3, and −6.5 kcal mol–1, respectively. Further, MD simulation studies of compound 6 suggested that the binding resulted in the stabilization of the CD81 molecule. Thus, all theoretical predictions associated with the experimental verifications motivated to discover novel approaches for cancer therapy.

Review on Liposome as Novel Approach for Cancer Therapy

The main objective is to study the importance of liposome in drug targeting in cancer cells andgo through various research work going through on liposome. The importance of liposomes to study the flexibility to couple with the specific ligands toachieve active targeting. Cancer can be treated by surgery, radiation, chemotherapy, gene therapy, immunotherapy, hormone therapy. Cancer is the uncontrolled growth of abnormal cell anywhere in a body. The abnormal cells aretermed cancer cells, malignant cells, or tumor cells. There were 14.1 million new cancer cases, 8.2 million cancer deaths and 32.6 million people living with cancer (within 5 years of diagnosis) in 2018 worldwide. 57% (8 million) of new cancer cases, 65% (5.3 million) of the cancer deaths and 48% (15.6 million) of the 5-year prevalent cancer cases occurred in the less developed regions.
 

Inhibitory Effects of Tangeretin, A Citrus Peel-Derived Flavonoid, on Breast Cancer Stem Cell Formation through Suppression of Stat3 Signaling.

Breast cancer stem cells (BCSCs) are responsible for tumor chemoresistance and recurrence. Targeting CSCs using natural compounds is a novel approach for cancer therapy. A CSC-inhibiting compound was purified from citrus extracts using silica gel, gel filtration and high-pressure liquid chromatography. The purified compound was identified as tangeretin by using nuclear magnetic resonance (NMR). Tangeretin inhibited cell proliferation, CSC formation and tumor growth, and modestly induced apoptosis in CSCs. The frequency of a subpopulation with a CSC phenotype (CD44+/CD24−) was reduced by tangeretin. Tangeretin reduced the total level and phosphorylated nuclear level of signal transducer and activator of transcription 3 (Stat3). Our results in this study show that tangeretin inhibits the Stat3 signaling pathway and induces CSC death, indicating that tangeretin may be a potential natural compound that targets breast cancer cells and CSCs.

Understanding the Mechanisms of Resistance to CAR T-Cell Therapy in Malignancies.

Taking advantage of the immune system to exert an antitumor effect is currently a novel approach in cancer therapy. Adoptive transfer of T cells engineered to express chimeric antigen receptors (CARs) targeting a desired antigen has shown extraordinary antitumor activity, especially in refractory and relapsed B-cell malignancies. The most representative in this respect, as well as the most successful example, is CD19 CAR T-cell therapy in B-cell acute lymphoblastic leukemia (B-ALL). However, with the widespread use of CAR T-cell therapy, problems of resistance and relapse are starting to be considered. This review provides a comprehensive picture of the mechanisms of resistance to CAR T-cell therapy from three aspects, namely, CAR T-cell factors, tumor factors, and tumor microenvironment factors, offering insights for improving CAR T-cell therapy.

Eupalinolide J Suppresses the Growth of Triple-Negative Breast Cancer Cells via Targeting STAT3 Signaling Pathway.

Persistent activation of STAT3 plays an important role in the development of triple-negative breast cancer (TNBC), and suppression of STAT3 is considered as a novel approach for cancer therapy. In this project, we aimed to examine the anticancer activity and molecular mechanism of eupalinolide J (EJ) in TNBC cells. The presented results demonstrated that the growth of human TNBC cells (MDA-MB-231 and MDA-MB-468 cells) was obviously inhibited by EJ. The IC50 values were 3.74 ± 0.58 and 4.30 ± 0.39 μM, respectively. Further study demonstrated that EJ suppressed the proliferation of TNBC cells mainly through cell apoptosis induction, mitochondrial membrane potential (MMP) disruption, and cell cycle arrest. Meanwhile, the STAT3 and p-STAT3 in EJ-treated TNBC cells were remarkably suppressed. Importantly, silencing of STAT3 by STAT3-shRNA significantly blunted the anticancer activities of EJ in TNBC cells, suggesting that EJ suppressed cancer cell proliferation via targeting the STAT3 pathway. Notably, further study demonstrated that EJ significantly promoted the degradation of STAT3 in TNBC cells. Finally, EJ exhibited an effective antitumor activity against MDA-MB-231 cells in vivo. In conclusion, we identified that EJ suppressed the growth of TNBC cells via targeting the STAT3 signaling pathway. These results strongly support that EJ is a promising therapeutic agent for TNBC.

Abstract 2699: Targeting an ubiquitin-activating enzyme in small-cell lung cancer (SCLC)

Abstract Background: Despite valiant efforts to improve patient outcomes, small cell lung cancer (SCLC) (~15-17% of lung cancer) remains an aggressive lung cancer, with an overall five-year survival of 7%. Current first-line therapy (chemotherapy+/-radiation) has not changed in 30+ years. TAK-243, an inhibitor of the ubiquitin activating enzyme (UAE), E1 (encoded by UBA1), poses a novel approach for cancer therapy. TAK-243 limits the formation of ubiquitin conjugates that ultimately mediate many cellular processes, including DNA repair signalling and protein degradation. Consequently, TAK-243 may disrupt cancer-specific dependencies of UAE to induce malignant cell death, and potentiate radiation-induced DNA damage. The discovery publication revealed that TAK-243 is especially potent in 2 SCLC cell-lines compared to healthy breast and fibroblastic tissues. With these limited data, the potential benefit of this novel agent as monotherapy and in combination with chemotherapy for SCLC has yet to be elucidated. Methods: We assessed the anti-proliferative effect of TAK-243 monotherapy in a large panel (n = 10) of variant and classical SCLC cell-lines, including assorted MYC family member amplifications and different UBA1 mRNA expression levels. TAK-243 EC50 single agent doses were determined by treating cell-lines with incremental concentrations of TAK-243 (0-1μM). For combinatorial analysis, TAK-243 (0-1μM) was administered to cell-lines alongside cisplatin/etoposide (CE) at cell-line specific optimized doses yielding 30-35% kill by CE. Short-term efficacy was determined by a cell viability resazurin assay, 48 hours after treatment initiation. ΔEC50 was measured as the single agent EC50 subtracted by the EC50 of TAK-243+CE. Positive ΔEC50 values show potential synergy between TAK-243 and CE. Results: Single-agent therapy. SCLC cell-lines demonstrated a range of sensitives to TAK-243 monotherapy after 48 hours. The cell-lines tested are ranked from highest to lowest sensitivity: NCI-H82, NCI-H69, NCI-H1618, LX22 (ex-vivo cultured PDX), NCI-H1092, NCI-H446, SHP77 and NCI-H196; with EC50 values ranging from 18nM to 80nM. However, NCI-H526, NCI-H889, and SBC-5 were non-responsive to therapy at 1μM. Combination therapy. TAK-243 upon combination treatment with CE revealed ΔEC50 values ranging from 5.23-14.54nM. NCI-H82, NCI-H69, SHP77 and NCI-H1092 demonstrated potential chemosensitivity to combination treatment. Conclusions: These data begin to hint at synergy between TAK-243 and CE, where lower doses of TAK-243 may be required for certain SCLC cell-lines when used in combination. These preliminary results suggest that TAK-243 may have the potential to improve the current SCLC standard therapies in molecular defined subgroups. These results are being confirmed in additional cell-lines and through in vivo experiments using patient-derived xenograft models of SCLC. *S.M and M.K.A contributed equally to this work Citation Format: Safa Majeed, Mansi K. Aparnathi, Lifang Song, Aaron D. Schimmer, Ming S. Tsao, Geoffrey Liu, Benjamin H. Lok. Targeting an ubiquitin-activating enzyme in small-cell lung cancer (SCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2699.

Effect of Ultrasound Combined With Microbubble Therapy on Interstitial Fluid Pressure and VX2 Tumor Structure in Rabbit.

Interstitial fluid pressure (IFP) in tumor tissue is significantly higher than that in normal tissue, which reduces the effectiveness of therapeutic drugs. There are several methods to decrease the IFP, such as normalizing blood vessel, decreasing hyaluronic acid and collagen fiber content in the extracellular matrix (ECM), and recovering lymphatic function. Reducing tumor IFP might be developed as a novel approach in cancer therapy. In this study, we aimed to elucidate the relationship between ultrasound combined with microbubble therapy and IFP, and the associated mechanism. VX2 tumor in rabbit was treated with ultrasound combined with microbubbles at different intensities. The IFP was measured using the wick-in-needle (WIN) method. The collagen and reticular fibers were stained by Masson and Gordon–Sweets, respectively. The results showed that low-frequency non-focus ultrasound combined with microbubbles therapy influences the IFP in tumor tissues; low-frequency non-focus ultrasound with low pressure increased the IFP, whereas middle–high pressure decreased the IFP. The results showed that the structure and content of collagen and reticular fibers in tumor tissue were rarely influenced by the treatment. Our study provides a novel approach of reduced IFP antitumor therapy.

Methylation-mediated repression of MiR-424/503 cluster promotes proliferation and migration of ovarian cancer cells through targeting the hub gene KIF23

ABSTRACT Ovarian cancer is one type of gynecological malignancies with extremely high lethal rate. Abnormal proliferation and metastasis are regarded to play important roles in patients’ death, whereas we know little about the underlying molecular mechanisms. Under this circumstance, our current study aims to investigate the role of hub genes in ovarian cancer. Bioinformatics analysis of the data from GEO and analyses of ovarian cancer samples were performed. Then, the results showed that KIF23, a hub gene, was mainly related to cell cycle and positively associated with poor prognosis. Meanwhile, both miR-424-5p and miR-503-5p directly targeted to 3’UTR of KIF23 to suppress the expression of KIF23 and inhibit ovarian cancer cell proliferation and migration. Furthermore, we discovered that miR-424/503 was epigenetically repressed by hypermethylation in the promoter regions, which directly modulated the expression of KIF23 to improve the oncogenic performance of cancer cells in vitro. Together, our research certifies that miR-424/503 cluster is silenced by DNA hypermethylation, which promotes the expression of KIF23, thereby regulating the proliferation and migration of ovarian cancer cells. Interposing this process might be a novel approach in cancer therapy.

Anticancer potential of zinc oxide nanoparticles against cervical carcinoma cells synthesized via biogenic route using aqueous extract of Gracilaria edulis

Development of novel approach for cancer therapy, sparing healthy normal cells overcoming the limitation of available therapies is of prime importance for cervical cancer treatment. Recently metal oxide based chemotherapeutics has emanated as a promising approach for cancer therapy. Hence, the present study was carried out to assess the anticancer potential of zinc oxide nanoparticles (ZnONPs) synthesized using biogenic source, aqueous extract of Gracilaria edulis. The prepared ZnONPs were characterized using UV–Visible spectroscopy, FTIR, XRD, FESEM, EDX and HRTEM. The anticancer potential of ZnONPs against cervical cancer cell lines (SiHa cells) was evaluated using MTT and the mechanism of apoptosis was evaluated using various staining techniques. UV–Vis spectroscopy exhibited absorption band at 367 nm specific for ZnONPs and the average energy gap was calculated as 3.37 eV. Further characterization by XRD, TEM, and FESEM illustrated the formation of wurtzite structure (hexagonal phase) with size ranging between 20 and 50 nm. EDS of SEM analysis confirmed the presence of Zn and O, which was further substantiated by XPS analysis. PL emission studies showed UV emission peak at 387 nm and broad visible emission peak at 520 nm. Zeta potential value of −28.2 mV depicted the stability of ZnONPs in the dispersion medium. Results of anticancer potential illustrated that ZnONPs exhibited cytotoxic effect against SiHa cells in a dose dependent manner with IC50 value of 35 ± 0.03 μg/ml. AO/EtBr dual staining, JC-1 staining, Hoechst 33258 nuclear staining and comet assay illustrated the ZnONPs induced ROS mediated mitochondrial dependent apoptotic cell death in SiHa cells. Further, flow cytometric analysis using Annexin V/FITC dye demonstrated that ZnONPs induced both apoptotic and necrotic mediated death in SiHa cells. Over all the results conclude that ZnONPs synthesized using algal sources might act as a new medicinal approach for the treatment of cervical carcinoma in conjugation with the current therapy.

Effect of UBE2Q on BECN and CEA Protein in Colorectal Cancer Cells

Background: Expression of UBE2Q1, UBE2Q2, and members of the ubiquitinconjugating enzyme family (E2) are affected in colorectal cancer (CRC). The BECN gene plays a key role in CRC cells. In gastrointestinal carcinoma therapy, tumorassociated antigens such as CEA are typically used.To investigate the association between UBE2Q1 and Beclin1 autophagy marker and CEA protein expression in LS180 CRC cell line. Materials and Methods: In this study, changes in the expression of BECN marker in LS180 cell lines with the vector containing UBE2Q1 were investigated using real-time PCR. The expression of CEA protein was also evaluated by western blotting. Statistical analyses were performed with Graph Pad Prism software. Results: The results indicated reduced expression of BECN autophagy marker (P=0). Therefore, in the presence of UBE2Q1, cancer cells have less ability to induce autophagy. However, CEA protein levels in LS180 transfected cells with a UBE2Q1- ORF-containing plasmid decreased when compared to non-transfected cells. Conclusion: The use of pharmacologic inhibitors related to the autophagy mechanism can be a novel approach in cancer therapy.

Mesoporous bioactive glasses (MBGs) in cancer therapy: Full of hope and promise

Implementing novel approaches for cancer therapy are under continuous progress, and bioactive glasses (BGs) and glass-ceramics show excellent potential in this regard. Although these materials have been mostly used as magnetic substances in hyperthermia approach, some of their subsets, i.e., mesoporous bioactive glasses (MBGs), have been recently proposed not only as magnetic materials but also as drug delivery systems for advanced treatment of bone cancer. Different types of MBGs including granular particles and three-dimensional (3D) scaffolds can be applied for cancer therapy. Based on the results obtained from in vitro studies, MBGs seem to have a bright future in the therapeutic strategies to combat cancer; however, their application in this field is still in its beginning, and more research needs to reveal all pros and cons of this newly proposed approach.

Induction of intrinsic apoptotic signaling pathway in A549 lung cancer cells using silver nanoparticles from Gossypium hirsutum and evaluation of in vivo toxicity

In the past decade, the research communities raised wide concerns on using medicinal plants for synthesis of nanomaterials due to its effective biological activity, lower side effects and also eco-friendly manner. Our previous report concentrated on the biomedical efficacy of fine characterized silver nanoparticles (AgNPs) from Gossypium hirsutum (cotton) leaf extract. Further, the current examination is planned to reveal the molecular mechanisms involving for activation of mitochondria-mediated signaling pathway by AgNPs in human lung cancer cells (A549) using various biological endpoints such as apoptotic induction by HOECHST 33342, AO/EtBr and Rhodamine 123 staining, cell cycle analysis using flow cytometry, gene and protein expressions by RT-PCR and immunoblotting respectively. This study was further extended to identify the toxicity of AgNPs using an animal model. Interestingly, we observed that A549 cells treated with AgNPs resulted in G2/M arrest and ultimately leads to induction of apoptosis cell death. Moreover, gene analysis demonstrated that diminished expression of anti-apoptotic (Bcl-2) and enhanced expression of pro-apoptotic (Bax) mitochondrial genes. The alterations in the gene pattern may interrupt of mitochondrial membrane potential which facilitates the releasing of cytochrome c (cyt c) into cytosol. The cyt c act as a key molecule for activation of caspases (9 and 3) to initiate intrinsic apoptotic signaling cell death process. The histological analysis proven the application of AgNPs in nanomedicine is quietly harmless and would not cause any discernible stress like swelling and inflammation to the organs of mice. Taken together, this investigation may provide solid evidence for cotton crop mediated AgNPs induced apoptosis cell death pathway and offer a novel approach for cancer therapy.