Removing a Cystein Group On Interferon Alpha 2b at Position 2 and 99 does Not Diminish Antitumor Activity of the

Heni Rachmawati1, Adhitya Jessica1, Yeyet Cahyati Sumirtaputra1

  • 1School of Pharmacy, Bandung Institute of Technology, Ganesha 10, 40132, Bandung, Indonesia.

Scientia Pharmaceutica
|April 26, 2016
PubMed

Insights

A modified interferon alpha 2b (IFNα2b) shows enhanced antitumor effects by promoting apoptosis in cancer cells. This mutein form of recombinant human IFNα2b (rhIFNα2b) warrants further investigation for cancer therapy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Immunology

Background:

  • Interferon alpha 2b (IFNα2b) is a standard therapeutic protein for hepatitis infections.
  • IFNα2b exhibits antitumor activity through antiproliferation and proapoptotic effects.
  • Recombinant human IFNα2b (rhIFNα2b) and its mutein forms have been developed for improved characteristics.

Purpose of the Study:

  • To evaluate the in vitro antitumor effect of a mutein rhIFNα2b compared to the native form and commercial rIFNα2b.
  • To investigate the underlying mechanisms of action, including effects on cell cycle and gene/protein expression.
  • To assess the proapoptotic activity of the mutein rhIFNα2b.

Main Methods:

  • HepG2 cells were treated with native and mutein rhIFNα2b.
  • MTT assay and cell viability tests were performed.
  • Cell cycle analysis via flow cytometry, and pSTAT1 and caspase 3 expression were analyzed.

Main Results:

  • No significant differences were observed in MTT assays or cell viability between the native and mutein forms.
  • Mutein rhIFNα2b demonstrated a trend towards enhanced proapoptotic activity.
  • Flow cytometry, pSTAT1, and caspase 3 expression supported the increased proapoptotic effect of the mutein form.

Conclusions:

  • The mutein rhIFNα2b exhibits comparable antiproliferative effects to the native form but shows improved proapoptotic activity.
  • The findings suggest that mutein rhIFNα2b may be a promising candidate for cancer therapy.
  • Further research into the molecular mechanisms of mutein rhIFNα2b is warranted.

Related Concept Videos

Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
4
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
9.9K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
2.1K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
65
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.1K
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
7.8K