Microplastics as a Modulator of Oncogenic Gene Expression and Oxidative Stress in Glioblastoma Cancer
Md. Mohiuddin Rahaman Rakib
Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh.
Shadia Shamim *
Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh.
Abu Jubaer Asif
Department of Pharmacy, Jagannath University, Dhaka, Bangladesh.
Raisa Islam
Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh.
Moushumi Kabir Anisa
Department of Pharmacy, School of Pharmacy and Public Health, Independent University, Bangladesh, Dhaka, Bangladesh.
Mamun Or Rashid
Department of Pharmacy, University of Chittagong, Chittagong, Bangladesh.
Anandy Islam
Department of Pharmacy, University of Chittagong, Chittagong, Bangladesh.
Tanvir Kabir
Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh.
*Author to whom correspondence should be addressed.
Abstract
Glioblastoma represents the most aggressive form of primary brain tumor and continues to exhibit significant resistance to standard treatment approaches. Emerging environmental contaminants, such as microplastics, have demonstrated the ability to induce oxidative stress and cellular dysfunction; nevertheless, their influence on glioblastoma progression remains inadequately understood. The study proposed that exposure to microplastics influences the expression of oncogenic genes and leads to oxidative stress-related cytotoxic and proliferative changes in glioblastoma cells. In this study, U87MG cells were subjected to escalating concentrations of microplastics, and various parameters such as proliferation, reactive oxygen species (ROS) production, cytotoxicity, tumorsphere formation, and cancer-related gene expression were assessed. The treatment of microplastics led to a dose-dependent rise in ROS production, suggesting notable oxidative stress, which was somewhat mitigated by the antioxidant limonene. Increased levels of reactive oxygen species (ROS) were linked to a rise in lactate dehydrogenase (LDH) release, indicating heightened membrane permeability and cytotoxic effects. Cellular stress and apoptotic signaling were indicated by morphological changes observed after exposure. Proliferation assays indicated a tendency for increased cell growth at elevated concentrations, whereas tumorsphere analysis showed larger sphere sizes, implying improved survival or expansion of mesenchymal-like subpopulations. Gene expression profiling demonstrated a notable increase in the expression of critical oncogenic and stress-related genes, such as PIK3CA, FZD1, TP53, TGFB1, FADD, PTEN, and CDKN2A, suggesting the activation of PI3K/AKT, Wnt, and oxidative stress response pathways. The findings collectively indicate that microplastics serve as modulators of redox homeostasis and oncogenic signaling in glioblastoma cells. Microplastic-induced oxidative stress seems to play a role in changing gene expression, causing cytotoxicity, and promoting tumor-associated characteristics, indicating a possible environmental factor in the progression of glioblastoma. This investigation emphasizes microplastics as a significant element in cancer toxicology and stresses the necessity for additional exploration into their impact on brain tumor biology.
Keywords: Microplastic, glioblastoma, U87MG, cancer