Cell-type specific anti-cancerous effects of nitro-oleic acid and its combination with gamma irradiation

Tomas Perecko1, Jana Pereckova1, Zuzana Hoferova1

  • 1Institute of Biophysics of the Czech Academy of Sciences, Kralovopolska 135, CZ-612 00 Brno, Czech Republic.

Biological Chemistry
|September 15, 2023
PubMed

Insights

Nitro-fatty acids (NFAs), like nitro-oleic acid (NO2OA), show anti-cancer properties and enhance radiation therapy effectiveness. Further research into NFAs could improve cancer chemoradiation treatments.

Area of Science:

  • Lipid biochemistry
  • Molecular oncology
  • Cancer therapeutics

Background:

  • Nitro-fatty acids (NFAs) are endogenous lipid mediators involved in post-translational protein modifications.
  • NFAs possess potential anti-cancer properties that warrant investigation for therapeutic applications.

Purpose of the Study:

  • To investigate the anti-cancer effects of nitro-oleic acid (NO2OA) alone and in combination with gamma irradiation.
  • To analyze the impact of NO2OA on cancer cell death, cell cycle, and specific protein expression.
  • To evaluate the radiosensitizing potential of NO2OA in cancer cell lines.

Main Methods:

  • Assessed NO2OA effects on cell viability, apoptosis, cell cycle distribution, and p21/cyclin D1 protein levels in various cancer and normal cell lines.
  • Determined the Dose Enhancement Ratio at 50% survival fraction (DERIC50) for NO2OA pre-treated cells followed by gamma irradiation.
  • Utilized cancer cell lines (A-549, HT-29, FaDu) and normal cell lines (HGF, HFF-1) for comparative analysis.

Main Results:

  • NO2OA suppressed cancer cell viability and induced apoptotic cell death in a cell line-specific manner.
  • HT-29 cells demonstrated higher sensitivity to NO2OA, exhibiting G2/M phase cell cycle arrest with altered p21 and cyclin D1 expression.
  • Pre-treatment with NO2OA significantly increased the DERIC50, indicating radiosensitizing effects, particularly in HT-29 cells.

Conclusions:

  • NO2OA exhibits anti-cancer activity and potentiates the effects of gamma irradiation, suggesting its potential in combined chemoradiotherapy.
  • The findings support the development of novel nitro-fatty acids with enhanced features for improved cancer chemoradiation strategies.
  • Nitro-oleic acid demonstrates promise as a radiosensitizer for enhancing cancer treatment efficacy.

Related Concept Videos

Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
1.3K
Cancer Therapies02:49

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
7.7K
2° Amines to N-Nitrosamines: Reaction with NaNO201:20

2° Amines to N-Nitrosamines: Reaction with NaNO2

Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.
4.3K
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...
7.7K
Biological Effects of Radiation02:59

Biological Effects of Radiation

All radioactive nuclides emit high-energy particles or electromagnetic waves. When this radiation encounters living cells, it can cause heating, break chemical bonds, or ionize molecules. The most serious biological damage results when these radioactive emissions fragment or ionize molecules. For example, α and β particles emitted from nuclear decay reactions possess much higher energies than ordinary chemical bond energies. When these particles strike and penetrate matter, they...
15.5K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K