Apoptosis-inducing, anti-angiogenic and anti-migratory effects of a dinuclear Pd(II) complex on breast cancer: A promising novel compound.

Because of the high mortality and morbidity rate of breast cancer, successful management of the disease requires synthesis of novel compounds. To this end, ongoing attempts to create new candidates include synthesis of multinuclear metal complexes. The high DNA binding affinity and cytotoxic activity of these complexes makes them promising as breast cancer treatments. This study investigated anti-growth/cytotoxic effect of the dinuclear Pd(II) complex on breast cancer cell lines (MCF-7, MDA-MB-231) using various methods of staining, flow cytometry, and immunoblotting. The study conducted colony formation, invasion, and migration assays were to assess the effect of the complex on metastasis. Increased caspase-3/7 levels and positive annexin V staining were observed in both cell lines, proving apoptosis. Altered TNFR1 and TRADD expression with caspase-8 cleavage followed by BCL-2 inactivation with loss of mitochondrial membrane potential confirmed the presence of apoptosis in MCF-7 and MDA-MB-231, regardless of p53 expression status. The results implied anti-migration properties. Finally, the study used the CAM assay to assess antiangiogenic properties and showed that the complex inhibited angiogenesis. The study concluded the dinuclear Pd(II) complex warrants further in vivo experiments to show its potential in the treatment of breast cancer.

Highly Promising Antitumor Agent of a Novel Platinum(II) Complex Bearing a Tetradentate Chelating Ligand.

A new mononuclear cationic platinum(II) coordination compound with 6,6'-bis(NH-benzimidazol-2-yl)-2,2'-bipyridine (L) ligand having N4-tetradentate binding pocket [Pt(L)]Cl2·2H2O (Complex 1) was synthesized and characterized by FT-IR(ATR), UV-vis, 1H NMR, APCI and MALDI MS, and CHN analysis. The antigrowth effect of Complex 1 was tested in breast cancer (MDA-MB-231), lung cancer (A549), colorectal cancer (HCT-116), prostate cancer (PC-3) cell lines, and bronchial epithelial cell line (BEAS-2B) by the SRB and ATP cell viability assays. Apoptosis was detected with Annexin V, mitopotential, BCL-2 inactivation, and γH2AX assays by flow cytometry. Complex 1 was found to have cytotoxic activity of MDA-MB-231, A549, HCT-116, and PC-3 cancer cell lines in a dose-dependent manner for 48 h. Complex 1 has been found to cause cell death through different mechanisms depending on the type of cancer. The findings indicated that complex induced intrinsic apoptosis with the increased mitochondrial membrane depolarization level, Bcl-2 inactivation, and DNA damage in PC-3 and A549 cell lines.

Key actors in cancer therapy: epigenetic modifiers.

Epigenetic reprogramming plays a crucial role in the tumorigenicity and maintenance of tumor-specific gene expression that especially occurs through DNA methylation and/or histone modifications. It has well-defined mechanisms. It is known that alterations in the DNA methylation pattern and/or the loss of specific histone acetylation/methylation markers are related to several hallmarks of cancer, such as drug resistance, stemness, epithelial-mesenchymal transition, and metastasis. It has also recently been highlighted that epigenetic alterations are critical for the regulation of the stemlike properties of cancer cells (tumor-initiating cells; cancer stem cells). Cancer stem cells are thought to be responsible for the recurrence of cancer which makes the patient return to the clinic with metastatic tumor tissue. Hence, the dysregulation of epigenetic machinery represents potential new therapeutic targets. Therefore, compounds with epigenetic activities have become crucial for developing new therapy regimens (e.g., antimetastatic agents) in the fight against cancer. Here, we review the epigenetic modifiers that have already been used in the clinic and/or in clinical trials, related preclinical studies in cancer therapy, and the smart combination strategies that target cancer stem cells along with the other cancer cells. The emerging role of epitranscriptome (RNA epigenetic) in cancer therapy has also been included in this review as a new avenue and potential target for the better management of cancer-beneficial epigenetic machinery.