Vol 24, No 14 (2024)

Oncology

A Systematic Review and Meta-analysis of the Relationship between Statin Intake and Esophageal Cancer

Khaghani A., Kasiri K., Heidari-Soureshjani S., Sherwin C., Mardani-Nafchi H.

Abstract

Background:Esophageal cancer is a malignant tumor with a low survival rate. Statins, commonly prescribed for their lipid-lowering effects, have been suggested to possess potential chemopreventive properties against various cancers, including esophageal cancer.

Objectives:This systematic review studied the association between statin intake and esophageal cancer.

Methods:To conduct this systematic review and meta-analysis, we reviewed studies published between 1980 and June 2023 in Web of Science (WOS), Embase, MEDLINE/PubMed, Scopus, and Cochrane Library databases according to the PRISMA guidelines. Data extraction, quality assessment, and statistical analyses were performed using predefined protocols. We used various statistical tests conducted by Stata statistical software. Statistical significance was considered significant at p < 0.05.

Results:Twenty-one studies were collected and analyzed. The meta-analysis demonstrated that the odds ratio (OR) of esophageal cancer in patients treated with statins was 0.65 (95% CI: 0.57-0.75, p < 0.001) compared to the non-receiving group. The ORs for case-control and cohort studies were 0.67 (95% CI:0.54-0.83, p < 0.001) and 0.62 (95% CI:0.55-0.71, p < 0.001), respectively. The investigation into the relationship between the statins intake and the incidence of esophageal cancer did not reveal any indication of publication bias according to both Begg's test (p = 0.966) and Egger's test (p = 0.113).

Conclusion:The results revealed that the odds of esophageal cancer in patients treated with statins decreased by 35% compared to patients not treated with statins. However, further well-designed prospective studies are needed to validate these findings and understand the underlying mechanisms of statins in preventing esophageal cancer.

Anti-Cancer Agents in Medicinal Chemistry. 2024;24(14):1029-1037
pages 1029-1037 views

Antidepressant Sertraline Hydrochloride Inhibits the Growth of HER2+ AU565 Breast Cancer Cell Line through Induction of Apoptosis and Cell Cycle Arrest

Fayyaz S., Atia-Tul-Wahab ., Irshad R., Siddiqui R., Choudhary M.

Abstract

Background:Drug repurposing in oncology promises benefits to many patients through its ability to provide novel, and fast-tracked treatments. Previous studies have demonstrated that depression may influence tumor progression. Anti-proliferative activity of certain antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), are reported in the literature.

Objective:This study was conducted to repurpose selective serotonin reuptake inhibitors (SSRIs) for the treatment of breast cancers, and it merits further validation and research.

Experimental:Changes in cell morphology were studied using DAPI staining, while the Annexin V/PI method was employed for apoptotic analysis. The expression of specific genes involved in cancer progression was also analyzed via RT-PCR. Caspase-3 activation was measured through fluorometric assay.

Results:We have identified that sertraline hydrochloride significantly inhibited the growth of breast cancer cell in vitro. Preliminary mechanistic studies demonstrated that the cytotoxicity of sertraline hydrochloride was possibly through the induction of apoptosis, as inferred from enhanced nuclear fragmentation, flow cytometric data, and caspase-3/7 activation. Gene expression analysis also showed an increased expression of pro-apoptotic Bax, and a slight decrease in oncogene c-myc in the presence of sertraline hydrochloride.

Conclusion:In conclusion, our study suggest that sertraline hydrochloride, an antidepressant drug, can potentially be used for the treatment of breast cancer.

Anti-Cancer Agents in Medicinal Chemistry. 2024;24(14):1038-1046
pages 1038-1046 views

Evaluation of Novel Benzo-annelated 1,4-dihydropyridines as MDR Modulators in Cancer Cells

Werner P., Szemerédi N., Spengler G., Hilgeroth A.

Abstract

Background:Multidrug resistance (MDR) is the main problem in anticancer therapy today. Causative transmembrane efflux pumps in cancer cells have been reconsidered as promising anticancer target structures to restore anticancer drug sensitivity by various strategies, including MDR modulators. MDR modulators interfere with the efflux pumps and improve the cellular efficiency of chemotherapeutics. So far, only a few candidates have gone through clinical trials with disappointing results because of low specificity and toxic properties.

Aim:This study aimed to find Novel MDR modulators to effectively combat multidrug resistance in cancer cells.

Objective:We synthesized various novel benzo-annelated 1,4-dihydropyridines to evaluate them as MDR modulators towards ABCB1 in cancer cells.

Methods:Synthesized compounds were purified by column chromatography. The MDR modulation of ABCB1 was determined in cellular efflux assays using the flow cytometry technique and cellular fluorescent measurements by the use of each fluorescent substrate.

Results:Compounds were yielded in a two-step reaction with structurally varied components. Further, substituent- dependent effects on the determined MDR inhibiting properties towards ABCB1 were discussed. Cellular studies prove that there is no toxicity and restoration of cancer cell sensitivity towards the used anticancer drug.

Conclusion:Novel MDR modulators could be identified with favorable methoxy and ester group functions. Their use in both ABCB1 non-expressing and overexpressing cells proves a selective toxicity-increasing effect of the applied anticancer agent in the ABCB1 overexpressing cells, whereas the toxicity effect of the anticancer drug was almost unchanged in the non-expressing cells. These results qualify our novel compounds as perspective anticancer drugs compared to MDR modulators with nonselective toxicity properties.

Anti-Cancer Agents in Medicinal Chemistry. 2024;24(14):1047-1055
pages 1047-1055 views

Cerium Oxide Nanoparticles Synthesis using Alhagi Maurorum Leaf Extract and Evaluation of Their Cytotoxic Effect on Breast Cancer Cell Lines and Antibacterial Effects

Hosseini S., Khatami M., Asadollahi A., Yaghoobi H.

Abstract

Introduction:Green synthesis offers a fast, simple, and economical method for producing metallic nanoparticles.The basis of this method is to obtain nanoparticles using natural materials, such as plants, fungi, and bacteria, instead of harmful and expensive chemical-reducing agents. In this study, CeO2NPs were produced using Alhagi maurorum extract, and their anticancer and antibacterial activities were evaluated.

Methods:Alhagi maurorum extract was prepared according to a previously described protocol, and CeO2NPs were synthesized from the salt of this extract. The resulting nanoparticles were characterized using Transmission electron microscopy (TEM), scanning electron microscope (SEM), and X-ray diffraction (XRD) techniques. The antibacterial and cytotoxic effects of the nanoparticles were measured by MIC, MBC, and MTT assays, respectively. The results were analyzed using one-way analysis of variance (ANOVA) using Prism software.

Results:The MTT assay on breast cancer cell lines showed that the cytotoxic effect of CeO2NPs on cell lines was concentration-dependent. In addition, this nanoparticle was more effective against Gram-positive bacteria.

Conclusion:These nanoparticles can be used as cancer drug delivery systems with specific targeting at low concentrations in addition to anticancer treatments. It can also have biological and medicinal applications, such as natural food preservation and wound dressing.

Anti-Cancer Agents in Medicinal Chemistry. 2024;24(14):1056-1062
pages 1056-1062 views

Novel Piperazine Derivatives as Potent Antihistamine, Anti-Inflammatory, and Anticancer Agents, their Synthesis and Characterization

Rasheed A., Shetty K., Roy L., Kumar J.

Abstract

Introduction:In this study, a series of novel piperazine derivatives were synthesised with high-to-good yields, and their structural analogies were confirmed using FTIR, 1H-NMR, and LC-MS techniques.

Methods:The synthesised compounds were evaluated for antioxidant and antimicrobial activities. Among the four synthesised piperazine derivatives, compound PD-2 exhibited relatively good antioxidant activity, with an IC50 value of 2.396 µg/mL, while the other three derivatives showed moderate to low antioxidant activity. Furthermore, compound PD-2 displayed antimicrobial activity against Pseudomonas aeruginosa, a gram-negative bacterium, and Candida albicans, a fungus. However, all four compounds showed strong resistance against grampositive bacteria, Staphylococcus aureus.

Results:Additionally, compound PD-1 exhibited significant antihistamine activity, eliciting an 18.22% reduction in histamine levels. Both PD-1 and PD-2 demonstrated noteworthy anti-inflammatory activity in a dosedependent manner (5-10 µM), leading to the inhibition of nitrite production up to 39.42% and 33.7% at higher concentrations (10 µM) and inhibition of tumour necrosis factor-alpha (TNF-α) generation up to 56.97% and 44.73% at 10 µM, respectively. Additionally, both novel molecules PD-1 and PD-2 effectively restrained the growth of HepG2 cells in a manner that is dependent on the dosage up to 55.44% and 90.45% at the highest concentrations (100 µg/mL), respectively.

Conclusion:These findings substantiate the rationale for further investigation into the novel series of persuasive piperazine analogues as potential agents with anti-inflammatory, antihistamine and anticancer properties.

Anti-Cancer Agents in Medicinal Chemistry. 2024;24(14):1063-1073
pages 1063-1073 views

Moscatilin Reverses EMT Progression and its Resulting Enhanced Invasion and Migration by Affecting the TGF-β Signaling Pathway in Bladder Cancer

Li Z., Yang J., Chen L., Chen P., Liu C., Long X., Chen B., Long J.

Abstract

Background:Bladder cancer metastasis is an essential process in the progression of muscle-invasive bladder cancer. EMT plays a crucial role in facilitating the spread of cancer cells. Identifying compounds that can inhibit these abilities of cancer cells is a significant international endeavor.

Objective:To explore the migration and invasion effect of Moscatilin on the bladder and clarify the mechanism of action

Methods:The anti-bladder cancer effect of Moscatilin was observed by a cell proliferation experiment. The migration and invasion of bladder cancer cells inhibited by Moscatilin were detected by Transwell and Wound healing. The effects of Moscatilin on EMT-related proteins E-cadherin, N-cadherin, Snail1, Vimentin, and TGF-β signaling pathways were detected by Western blot, and nucleic acid levels were verified by qPCR.

Results:Our study revealed that Moscatilin reduced the viability of bladder cancer cells in vitro and impeded their migration and invasion in experimental settings. Furthermore, we observed that Moscatilin decreased the activation levels of active proteins, specifically Smad3, Samd2, and MMP2. Additionally, we found that moscatilin significantly reduced the expression level of TGF-β and was also capable of reversing the overexpression effect of TGF-β. Treatment with Moscatilin also led to significant inhibition of interstitial cell markers Ncadherin and Snail1, which are associated with EMT.

Conclusion:These findings indicate that Moscatilin impedes the migration and invasion of bladder cancer cells by influencing cell survival, modulating TGF-β/Smad signaling, and inhibiting EMT.

Anti-Cancer Agents in Medicinal Chemistry. 2024;24(14):1074-1084
pages 1074-1084 views

Preparation of a Novel Multifunctional Cationic Liposome Drug-carrying System and its Functional Study on Lung Cancer

Kong Y., Xu L., Cao J.

Abstract

Background:Low-dose chemotherapy is a promising treatment strategy that may be improved by controlled delivery.

Objective:This study aimed to design polyethylene glycol-stabilized bilayer-decorated magnetic Cationic Liposomes (CLs) as a drug delivery system for integrated functional studies of lung cancer cell therapy and imaging.

Methos:A novel multifunctional folic acid targeting magnetic CLs docetaxel drug-loading system (FA-CLs-Fe- DOC) was prepared and tested for its physical properties, encapsulation rate and drug release performance. The feasibility of FA-CLs-Fe-DOC ability to inhibit tumor cells and act as an MRI contrast agent was investigated in vitro, and the target recognition and therapeutic ability of FA-CLs-Fe-DOC was studied in vivo.

Results:FA-CLs-Fe-DOC had a particle size of 221.54 ± 6.42 nm and a potential of 28.64 ± 3.56 mv, with superparamagnetic properties and better stability. The encapsulation rate was 95.36 ± 1.63%, and the drug loading capacity was 9.52 ± 0.22%, which possessed the drug slow-release performance and low cytotoxicity and could effectively inhibit the proliferation of lung cancer cells, promoting apoptosis of lung cancer cells. MRI showed that it had the function of tracking and localization of lung cancer cells. In vivo experiments confirmed the targeted recognition property and therapeutic function of lung cancer cells.

Conclusion:In this study, we successfully prepared an FA-CLs-Fe-DOC capable of specifically targeting lung cancer cells with integrated functions of efficient lung cancer cell killing and imaging localization. This targeted drug packaging technology may provide a new strategy for the design of integrated carriers for targeted cancer therapy and imaging.

Anti-Cancer Agents in Medicinal Chemistry. 2024;24(14):1085-1095
pages 1085-1095 views