Preliminary evaluation of antiproliferative and apoptotic activities of novel indolin-2-one derivatives.

Indole-based agents are frequently used in targeted or supportive therapy of several cancers. In this study, we investigated the anticancer properties of originally synthesized novel indolin-2-one derivatives (6a-d) against Malignant Mesothelioma, Breast cancer, and Colon Cancer cells. Our results revealed that all derivatives were effectively delayed cell proliferation by inhibiting the ERK1/2, AKT, and STAT3 signaling pathways in a concentration-dependent manner.

A network-based drug prioritization and combination analysis for the MEK5/ERK5 pathway in breast cancer.

Background: Prioritizing candidate drugs based on genome-wide expression data is an emerging approach in systems pharmacology due to its holistic perspective for preclinical drug evaluation. In the current study, a network-based approach was proposed and applied to prioritize plant polyphenols and identify potential drug combinations in breast cancer. We focused on MEK5/ERK5 signalling pathway genes, a recently identified potential drug target in cancer with roles spanning major carcinogenesis processes.

A systems pharmacology approach based on oncogenic signalling pathways to determine the mechanisms of action of natural products in breast cancer from transcriptome data.

Background: Narrow spectrum of action through limited molecular targets and unforeseen drug-related toxicities have been the main reasons for drug failures at the phase I clinical trials in complex diseases. Most plant-derived compounds with medicinal values possess poly-pharmacologic properties with overall good tolerability, and, thus, are appropriate in the management of complex diseases, especially cancers. However, methodological limitations impede attempts to catalogue targeted processes and infer systemic mechanisms of action.

Anticarcinogenic effects of halofuginone on lung-derived cancer cells.

Malignant mesothelioma is a rare but aggressive form of malignancy, which is difficult to diagnose and is resistant to current chemotherapeutic treatment options. Molecular techniques have been used to investigate the mechanisms of action and the beneficial therapeutic effects of halofuginone (HF) in several cancers but not malignant mesotheliomas. In this study, the antiproliferative and apoptotic effects of HF were investigated through its ability to deregulate EGFR downstream signalling cascade proteins in the pathologically aggressive malignant mesothelioma and non-small-cell lung cancer cells.

Effects of human sperm cryopreservation on apoptotic markers in normozoospermic and non-normozoospermic patients.

SummaryThe negative effects of cryopreservation on sperm parameters are well documented but little information is known about molecular basis of the process. The aim of the present study was to investigate the possible effects of sperm cryopreservation on main apoptotic signs including DNA fragmentation and caspase-3 activation and to determine if these effects vary according to sperm parameters. Sperm samples of 72 patients were cryopreserved.

Eradicating Quiescent Tumor Cells by Targeting Mitochondrial Bioenergetics.

The presence of quiescent cell populations in solid tumors represents a major challenge for disease eradication. Such cells are generally present in poorly vascularized tumor areas, show limited sensitivity to traditional chemotherapeutical drugs, and tend to resume proliferation, resulting in tumor reseeding and growth. There is growing recognition of the importance of developing therapies that target these quiescent cell populations to achieve long-lasting remission.

EGFR-dependent signalling reduced and p38 dependent apoptosis required by Gallic acid in Malignant Mesothelioma cells.

The unrestrained EGFR signalling contributes to malignant phenotype in a number of cancers including Malignant Mesotheliomas. Present study was designed to evaluate EGFR-dependent anti-proliferative and apoptotic effects of Gallic acid in transformed Mesothelial (MeT-5A) and Malignant Mesothelioma (SPC212) cells. Gallic acid reduced the viability of Malignant Mesothelioma cells in a concentration and time-dependent manner.

Quercetin and Cisplatin combined treatment altered cell cycle and mitogen activated protein kinase expressions in malignant mesotelioma cells.

Background: Malignant mesothelioma is a locally aggressive and highly lethal neoplasm of pleural, peritoneal and pericardial mesothelial cells without successful therapy. Previously, we reported that Quercetin in combination with Cisplatin inhibits cell proliferation and activates caspase-9 and -3 enzymes in different malignant mesothelioma cell lines. Moreover, Quercetin + Cisplatin lead to accumulation of both SPC111 and SPC212 cell lines in S phase.