The nucleoside antagonist cordycepin causes DNA double strand breaks in breast cancer cells.

The fungal drug cordycepin (3-deoxyadenosine) is known to exert anti-tumor activities, preferentially by interfering with RNA synthesis. We have investigated the effect of cordycepin on human breast epithelial cell lines, ranging from non-malignant MCF10A cells to highly de-differentiated MDA-MB-435 cancer cells. Treatment of human breast cancer cells with cordycepin caused either apoptosis or persistent cell cycle arrest that was associated with reduced clonal growth of cordycepin-treated breast cancer cells.

The HIV reverse transcriptase inhibitor tenofovir induces cell cycle arrest in human cancer cells.

Selected HIV drugs, either of the protease inhibitor type or the nucleoside antagonist type, have been shown to exert tumoricidal effects. Here, we show that the HIV reverse transcriptase inhibitor Truvada, a combination drug of the cytidine analogue emtricitabine and the adenosine analogue tenofovir, induces DNA damage and cell cycle arrest in human cancer cells. Phosphorylation of the DNA repair enzyme H2AX by emtricitabine/tenofovir indicated that it interfered with the integrity of the DNA and replication machinery in human cancer cells.

Nelfinavir induces mitochondria protection by ERK1/2-mediated mcl-1 stabilization that can be overcome by sorafenib.

The HIV protease inhibitor nelfinavir is an investigational drug for cancer treatment. We have previously demonstrated induction of apoptosis by nelfinavir even in chemo-resistant ovarian cancer cells. In contrast to the pro-apoptotic effect of nelfinavir on human cancer cells, we noticed a significant upregulation of the anti-apoptotic mitochondrial membrane protein mcl-1 by nelfinavir, resulting in a mitochondria-independent induction of apoptosis.

Nelfinavir induces the unfolded protein response in ovarian cancer cells, resulting in ER vacuolization, cell cycle retardation and apoptosis.

Proteasome inhibitors and protease inhibitors are currently being discussed to be useful to sensitize drug-resistant cancer cells to chemotherapeutic agents or to act independently as single agents on drug-resistant cancer cells. We tested the effect of the clinically applied HIV protease inhibitor nelfinavir on ovarian cancer cells. Nelfinavir efficiently induced cell death in carboplatin-sensitive (SKOV3, OV-GH-5) and carboplatin-resistant (OVCAR3, OV-GH-1) ovarian cancer cell lines as well as in cancer biopsies and ascites samples from patients with recurrent ovarian cancer.

Bortezomib treatment of ovarian cancer cells mediates endoplasmic reticulum stress, cell cycle arrest, and apoptosis.

Bortezomib, an approved drug for the treatment of certain haematological neoplasms, is currently being tested in clinical trials as a potential therapeutic agent against several types of solid cancer, including ovarian cancer. We have analyzed the effect of bortezomib on ovarian cancer cells and tissue explants either as a single agent or in combination with carboplatin, taxol, or TRAIL (tumor necrosis factor-related apoptosis-inducing ligand). Bortezomib alone efficiently induced apoptosis in ovarian cancer cells.

Nelfinavir induces TRAIL receptor upregulation in ovarian cancer cells.

HIV protease inhibitors are currently being discussed to be useful as new and alternative anti-cancer agents, especially as second line treatments for chemo-resistant human cancer types. Among three clinically applied HIV protease inhibitors tested, we found a high efficacy of nelfinavir on ovarian cancer cells, accompanied by apoptosis (annexin binding) and necrosis (propidium iodide permeability). In vitro, at concentrations used to induce cell death in ovarian cancer cells, nelfinavir had no effect on the cellular viability of fibroblasts or peripheral blood mononuclear leukocytes.