Том 24, № 12 (2024)

Oncology

A Number of the N-terminal RASSF Family: RASSF7

Xu Y., Du W., Xiao Y., Gao K., Li J., Li S.

Аннотация

The Ras association domain family 7 (RASSF7, also named HRC1), a potential tumor-related gene, located on human chromosome 11p15, has been identified as an important member of the N-terminal RASSF family. Whereas, the molecular biological mechanisms of RASSF7 in tumorigenesis remain to be further established. We perform a systematic review of the literature and assessment from PUBMED and MEDLINE databases in this article. RASSF7 plays a significant role in mitosis, microtubule growth, apoptosis, proliferation and differentiation. Many research literature shows that the RASSF7 could promote the occurrence and advance of human tumors by regulating Aurora B, MKK4, MKK7, JNK, YAP, MEK, and ERK, whereas, it might inhibit c-Myc and thus lead to the suppression of tumorigenesis. The pregulation of RASSF7 often occurs in various malignancies such as lung cancer, neuroblastoma, thyroid neoplasm, hepatocellular cancer, breast cancer and gastric cancer. The expression stage of RASSF7 is positively correlated with the tumor TNM stage. In this review, we primarily elaborate on the acknowledged structure and progress in the various biomechanisms and research advances of RASSF7, especially the potential relevant signaling pathways. We hope that RASSF7 , a prospective therapeutic target for human malignancies, could play an available role in future anti-cancer treatment.

Anti-Cancer Agents in Medicinal Chemistry. 2024;24(12):889-895
pages 889-895 views

Liposomal Nano-Based Drug Delivery Systems for Breast Cancer Therapy: Recent Advances and Progresses

Yazdan M., Naghib S., Mozafari M.

Аннотация

Breast cancer is a highly prevalent disease on a global scale, with a 30% incidence rate among women and a 14% mortality rate. Developing countries bear a disproportionate share of the disease burden, while countries with greater technological advancements exhibit a higher incidence. A mere 7% of women under the age of 40 are diagnosed with breast cancer, and the prevalence of this ailment is significantly diminished among those aged 35 and younger. Chemotherapy, radiation therapy, and surgical intervention comprise the treatment protocol. However, the ongoing quest for a definitive cure for breast cancer continues. The propensity for cancer stem cells to metastasize and resistance to treatment constitute their Achilles' heel. The advancement of drug delivery techniques that target cancer cells specifically holds significant promise in terms of facilitating timely detection and effective intervention. Novel approaches to pharmaceutical delivery, including nanostructures and liposomes, may bring about substantial changes in the way breast cancer is managed. These systems offer a multitude of advantages, such as heightened bioavailability, enhanced solubility, targeted tumor destruction, and diminished adverse effects. The application of nano-drug delivery systems to administer anti-breast cancer medications is a significant subject of research. This article delves into the domain of breast cancer, conventional treatment methods, the incorporation of nanotechnology into managerial tactics, and strategic approaches aimed at tackling the disease at its core.

Anti-Cancer Agents in Medicinal Chemistry. 2024;24(12):896-915
pages 896-915 views

Wortmannin Inhibits Cell Growth and Induces Apoptosis in Colorectal Cancer Cells by Suppressing the PI3K/AKT Pathway

Bani N., Rahmani F., Shakour N., Amerizadeh F., Khalili-Tanha G., Khazaei M., Hassanian S., Kerachian M., Abbaszadegan M., Mojarad M., Hadizadeh F., Ferns G., Avan A.

Аннотация

Background:Colorectal cancer (CRC) remains a significant contributor to mortality, often exacerbated by metastasis and chemoresistance. Novel therapeutic strategies are imperative to enhance current treatments. The dysregulation of the PI3K/Akt signaling pathway is implicated in CRC progression. This study investigates the therapeutic potential of Wortmannin, combined with 5‐fluorouracil (5-FU), to target the PI3K/Akt pathway in CRC.

Methods:Anti-migratory and antiproliferative effects were assessed through wound healing and MTT assays. Apoptosis and cell cycle alterations were evaluated using Annexin V/Propidium Iodide Apoptosis Assay. Wortmannin's impact on the oxidant/antioxidant equilibrium was examined via ROS, SOD, CAT, MDA, and T-SH levels. Downstream target genes of the PI3K/AKT pathway were analyzed at mRNA and protein levels using RTPCR and western blot, respectively.

Results:Wortmannin demonstrated a significant inhibitory effect on cell proliferation, modulating survivin, cyclinD1, PI3K, and p-Akt. The PI3K inhibitor attenuated migratory activity, inducing E-cadherin expression. Combined Wortmannin with 5-FU induced apoptosis, increasing cells in sub-G1 via elevated ROS levels.

Conclusion:This study underscores Wortmannin's potential in inhibiting CRC cell growth and migration through PI3K/Akt pathway modulation. It also highlights its candidacy for further investigation as a promising therapeutic option in colorectal cancer treatment.

Anti-Cancer Agents in Medicinal Chemistry. 2024;24(12):916-927
pages 916-927 views

Ginsenoside Rb1 Inhibits the Proliferation of Lung Cancer Cells by Inducing the Mitochondrial-mediated Apoptosis Pathway

Feng L., Liu X., Sun K., Sun Y., Wu W., Chen C., Jin X., Wan X.

Аннотация

Background:Lung cancer is one of the more common malignant tumors posing a great threat to human life, and it is very urgent to find safe and effective therapeutic drugs. The antitumor effect of ginsenosides has been reported to be a treatment with a strong effect and a high safety profile.

Objective:This paper aimed to investigate the inhibitory effect of ginsenoside Rb1 on 95D and NCI-H460 lung cancer cells and its pathway to promote apoptosis.

Methods:We performed the CCK-8 assay, fluorescence staining assay, flow cytometry, scratch healing assay, and Transwell assay to detect the effects of different concentrations of ginsenoside Rb1 on the antitumor activity of 95D and NCI-H460 cells and Western Blot detected the mechanism of antitumor effect.

Results:Ginsenoside Rb1 treatment significantly increased the inhibition and apoptosis rates of 95D and NCIH460 cells and inhibited the cell cycle transition from S phase to G2/M. Rb1 induces apoptosis by altering the levels of P53, Bax, Cyto-c, Caspase-8, Caspase-3, Cleaved Caspase-3, Bcl-2, MMP-2, and MMP-9 proteins and activating the external apoptotic pathway.

Conclusion:Ginsenoside Rb1 inhibits proliferation and migration and induces apoptosis of 95D and NCI-H460 lung cancer cells by regulating the mitochondrial apoptotic pathway to achieve antitumor activity.

Anti-Cancer Agents in Medicinal Chemistry. 2024;24(12):928-941
pages 928-941 views

The Development of Organotin(IV) N-Ethyl-N-Benzyldithiocarbamate Complexes: A Study on Their Synthesis, Characterization, and Cytocidal Effects on A549 Cell Line

Abd Aziz N., Awang N., Kamaludin N., Mohamad Anuar N., Hamid A., Chan K., Arshad S.

Аннотация

Background:Organotin(IV) complexes of dithiocarbamate are vital in medicinal chemistry, exhibiting potential in targeting cancer cells due to their unique properties that enhance targeted delivery. This study aimed to synthesize and characterize organotin(IV) N-ethyl-N-benzyldithiocarbamate complexes (ONBDCs) and evaluate their cytotoxicity against A549 cells, which are commonly used as a model for human lung cancer research.

Method:The two ONBDC derivatives – ONBDC 1 (dimethyltin(IV) N-ethyl-N-benzyldithiocarbamate) and ONBDC 2 (triphenyltin(IV) N-ethyl-N-benzyldithiocarbamate) – were synthesized via the reaction of tin(IV) chloride with N-ethylbenzylamine in the presence of carbon disulfide. A range of analytical techniques, including elemental analysis, IR spectroscopy, NMR spectroscopy, UV-Vis spectrometry, TGA/DTA analysis, and X-ray crystallography, was conducted to characterize these compounds comprehensively. The cytotoxic effects of ONBDCs against A549 cells were evaluated using MTT assay.

Results:Both compounds were synthesized and characterized successfully via elemental and spectroscopies analysis. MTT assay revealed that ONBDC 2 demonstrated remarkable cytotoxicity towards A549 cells, with an IC50 value of 0.52 µM. Additionally, ONBDC 2 displayed significantly higher cytotoxic activity against the A549 cell line when compared to the commercially available chemotherapeutic agent cisplatin (IC50: 32 µM).

Conclusion:Thus, it was shown that ONBDC 2 could have important anticancer properties and should be further explored as a top contender for creating improved and specialized cancer treatments.

Anti-Cancer Agents in Medicinal Chemistry. 2024;24(12):942-953
pages 942-953 views

Primary Pulmonary Lymphoepithelioma-like Carcinoma: A Case Report Utilizing Camrelizumab and Anlotinib for Prolonged Survival

Lei S., Tian S., Lu S., Qing Z., Long J., Li L., Yang D.

Аннотация

Background:Primary Pulmonary Lymphoepithelioma-like Carcinoma (PPLELC) is a rare form of cancer for which no standard treatment has been established to date. Patients with advanced-stage PPLELC generally have a poor prognosis with overall survival of 22.7 months.

Case Presentation:Here, we report a case of advanced primary pulmonary lymphoepithelioma-like carcinoma. Initially, the patient underwent a first-line (GP) and a second-line (DP) of chemotherapy, which provided temporary relief but resulted in varying degrees of myelosuppression. When the disease progressed again, we administered a third-line treatment consisting of camrelizumab combined with anlotinib.

Result:This resulted in a progression-free survival of over 26 months without significant toxic side effects.

Conclusion:Our findings suggest that combining camrelizumab and anlotinib could lead to a long progressionfree survival in patients with advanced PPLELC.

Anti-Cancer Agents in Medicinal Chemistry. 2024;24(12):954-960
pages 954-960 views