LATEST UPDATES » Vol 26, Nos. 07 & 08, July & August 2022 – Engineering a Sustainable Future       » Improving Crop Yield With Leaf Angles       » Combatting Tumours at the Gut With Novel Oral Vaccine Made by Bacteria Robot       » New Carbon Capture System With Record-Breaking Efficiency to Revolutionise Direct Air Capture       » Simulating the Synergistic Interactions of Neurons and Synapses in Computing Devices       » Understanding Gene Functions: From Algae to Plants       » Colour-Modified Mice Tissues Allow for Higher-Resolution Imaging      
Vol 26, Nos. 07 & 08, July & August 2022   |   Issue PDF view/purchase
Scientists Unveil Why Non-Specific Occurrence of Multidrug-Resistance Arises During Tumour Therapy
Non-substrate chemicals have been shown to induce multidrug resistance by causing oxidative stress when tested on specific transporters.

Accounting for nearly one in six deaths, cancer is one of the leading causes of death worldwide. To treat cancer, chemotherapy is often applied to kill cancer cells. Unfortunately, cancers can develop resistance to therapies, thereby increasing the prevalence of drug-resistant cancers, which eventually develop into multidrug resistance thereby rendering most drugs ineffective. Now, researchers from the Suzhou Institute of Biomedical Engineering and Technology (SIBEBT) of the Chinese Academy of Sciences (CAS) have discovered several possible reasons why multi-drug resistance inevitably occurs during tumour therapy.

Of the many mechanisms of drug resistance, one of the most well-studied mechanisms is the induction of Adenosinetriphosphate (ATP)-binding cassette (ABC) transporters by chemotherapeutic drugs. Highly expressed in cancer cells, these transporters can pump out chemotherapeutics and make the treatment ineffective. According to a previous study, non-substrate nanoparticles could induce multidrug resistance by causing oxidative damage, indicating that multidrug resistance could be induced by not only the substrates but also oxidative damage.

To verify this claim, Yin Jian and his team at SIBEBT used a lung cancer cell line as a model to study the interaction of doxorubicin, ethanol, and hydrogen peroxide with ABC transporters. Doxorubicin is the substrate of ABC transporter and chemotherapeutic drugs, whereas ethanol and hydrogen peroxide are small-molecule compounds that are unrelated to the function of ABC transporter.

“When the three substances enter the cells, they can cause significant oxidative stress inside cells,” said Yin Jian.

With increased oxidative stress, the expression of transporters is elevated, which in turn decreases intracellular oxidative stress by effluxing oxidised glutathione. In this process, pregnane X receptor played an important regulatory role. These results indicate that non-substrate chemicals could also induce ABC transporter expressions like that of chemotherapeutic agents upon inducing oxidative damage. This phenomenon could be regarded as a non-specific feedback of tumour cells/ABC transporters to external stimuli.

With these results, the researchers successfully established the relationship between multidrug resistance mechanisms and oxidative stress. Their findings are expected to help innovate advanced strategies to enhance this mechanism to better combat ABC transporter-mediated multidrug resistance.

“Considering that peroxidative damage is the main source of the toxicity of current environmental pollutants, long-term exposure to environmental pollutants could not only induce direct toxicity, but also further threaten human health by inducing multi-drug resistance,” said Yin Huancai, another researcher from the study.

Source: Yuan et al. (2022). Oxidative stress-mediated up-regulation of ABC transporters in lung cancer cells. Journal of Biochemical and Molecular Toxicology, e23095.

MGI Makes Possible New Advances in Agrigenomics Research and Molecular Breeding
news 2022 PDA Pharmaceutical Manufacturing & Quality Conference
news Medtec China 2022 Gathers Medtech Leading Enterprises, Optimising Medical Equipment Supply Chain by Creating Online-Offline Promotion Platforms
news Medtec China 2022 Is Now Open for Visitor Registration, Helping Medical Device Manufacturers in Medtech Sourcing and Supply Chain Stabilisation
news Inaugural Asia Summit on Global Health highlights Hong Kong's advantages

About Us
Available issues
Editorial Board
Letters to Editor
Contribute to APBN
Advertise with Us
World Scientific Publishing Co. Pte. Ltd.
5 Toh Tuck Link, Singapore 596224
Tel: 65-6466-5775
Fax: 65-6467-7667
» For Editorial Enquiries:
   [email protected] or Ms Carmen Chan
» For Subscriptions, Advertisements &
   Media Partnerships Enquiries:
   [email protected]
Copyright© 2022 World Scientific Publishing Co Pte Ltd  •  Privacy Policy