Nelfinavir induces TRAIL receptor upregulation in ovarian cancer cells

Ansgar Brüning1, Marianne Vogel, Petra Burger

  • 1University Hospital Munich, Department of Obstetrics/Gynecology, Maistrasse 11, 80337 Munich, Germany. ansgar.bruening@med.uni-muenchen.de

Insights

Nelfinavir, an HIV protease inhibitor, effectively kills ovarian cancer cells via apoptosis and necrosis. It also sensitizes these cells to TRAIL therapy by upregulating DR5, offering a new anti-cancer strategy.

Area of Science:

  • Oncology
  • Virology
  • Pharmacology

Background:

  • HIV protease inhibitors are explored as novel anti-cancer agents, particularly for chemo-resistant cancers.
  • Nelfinavir is a clinically used HIV protease inhibitor with potential anti-cancer properties.

Purpose of the Study:

  • To evaluate the efficacy of nelfinavir against ovarian cancer cells.
  • To investigate nelfinavir's effect on cancer cell death pathways and its potential to sensitize cells to TRAIL therapy.

Main Methods:

  • In vitro testing of nelfinavir on ovarian cancer cells, fibroblasts, and peripheral blood mononuclear leukocytes.
  • Analysis of apoptosis and necrosis induction.
  • Assessment of TRAIL receptor DR5 expression via RT-PCR and FACScan.

Main Results:

  • Nelfinavir demonstrated high efficacy against ovarian cancer cells, inducing apoptosis and necrosis.
  • Nelfinavir did not affect the viability of normal cells (fibroblasts, leukocytes) at effective concentrations.
  • Nelfinavir sensitized ovarian cancer cells to TRAIL receptor antibody treatment by upregulating DR5.

Conclusions:

  • Nelfinavir is a potent agent against ovarian cancer cells.
  • Nelfinavir can enhance the effectiveness of TRAIL-based therapies for ovarian cancer.

Related Concept Videos

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates these...
Treatment Resistent Cancers02:56

Treatment Resistent Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists01:27

Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists

5-HT3 receptor antagonists, such as dolasetron, granisetron (Kytril), ondansetron (Zofran), and palonosetron (Axoli), are crucial in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea. These drugs selectively block 5-HT3 receptors in the visceral vagal and spinal afferent nerves, chemoreceptor trigger zone, and the vomiting center. They have a rapid onset of action and can be given as a single dose before chemotherapy. Ondansetron and granisetron, in particular,...