Selective tumor cell death induced by irradiated riboflavin through recognizing DNA G-T mismatch

Yi Yuan1,2, Yongyun Zhao1, Lianqi Chen1

  • 1Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China.

Nucleic Acids Research
|September 16, 2017
PubMed

Insights

Riboflavin (vitamin B2) targets G-T mismatches in DNA, inducing breaks under light. This selectively kills tumor cells lacking mismatch repair, suggesting G-T mismatches as a novel cancer drug target.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Photodynamic Therapy
  • Cancer Research

Background:

  • Riboflavin (vitamin B2) shows potential as an antitumoral agent in photodynamic therapy.
  • The precise molecular mechanisms underlying riboflavin's anticancer effects have remained unclear.
  • Photodynamic therapy applications are often limited by incomplete understanding of drug action.

Purpose of the Study:

  • To elucidate the molecular mechanism of riboflavin's antitumoral activity.
  • To investigate riboflavin's interaction with DNA and its effects under irradiation.
  • To explore the potential of targeting G-T mismatches in cancer therapy.

Main Methods:

  • Investigated riboflavin's DNA binding specificity.
  • Assessed riboflavin's ability to induce DNA strand breaks upon photo-irradiation.
  • Evaluated the selective killing of tumor cells with defective mismatch repair systems.

Main Results:

  • Riboflavin specifically recognizes and binds to G-T mismatch DNA sequences.
  • Photo-irradiation in the presence of riboflavin efficiently induces single-strand breaks in duplex DNA targets.
  • Tumor cells deficient in mismatch repair systems undergo selective cell death under riboflavin photo-irradiation.

Conclusions:

  • Riboflavin's mechanism involves specific G-T mismatch recognition and photo-induced DNA damage.
  • G-T mismatches represent a viable drug target for selective tumor cell destruction.
  • Riboflavin serves as a promising lead compound for developing novel anticancer drugs targeting DNA mismatches.

Related Concept Videos

Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
44.8K
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
5.3K
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
41.2K
Other Unique Bacteria01:18

Other Unique Bacteria

Magnetic bacteria exhibit a directed movement called magnetotaxis, driven by structures called magnetosomes. These magnetosomes consist of chains of magnetic particles made of either magnetite (Fe₃O₄) or greigite (Fe₃S₄) and are organized in a linear conformation by a protein scaffold within invaginations of the cell membrane. The bacteria align along the north–south magnetic field lines, much like a compass needle. They are typically microaerophilic or anaerobic...
494
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...
9.0K
Overview of DNA Repair02:25

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
34.2K