Exploring the in vitro effects of chronic Methamphetamine exposure on selected Cancer cell lines

Abstract

Methamphetamine (METH) is a potent psychostimulant widely associated with neurotoxicity and oxidative stress. Although its acute effects are well documented in multiple organ systems, the cellular consequences of chronic METH exposure in cancer biology remain poorly defined. Understanding how tumour cells respond to sustained psychostimulant-induced stress may provide insight into metabolic and redox adaptations relevant to cancer progression. Five cancer cell lines, namely MCF-7, MDA-MB-231, HeLa, U87, and SK-N-BE-2 cancer cells were exposed to physiological and supraphysiological concentrations of METH (0.1-250μM) chronically for 96 hours. Cell viability and proliferation were assessed using the trypan blue exclusion assay. Mitochondrial activity was evaluated using the XTT assay. Intracellular reactive oxygen species (ROS) levels were quantified using the H₂DCFDA assay. All measurements were analysed relative to controls to identify dose- and time-dependent trends. Across all five cell lines, chronic METH exposure did not induce cytotoxicity, as dead cell numbers remained comparable to controls at all time points. Instead, METH produced cytostatic modulation varied by cell line and concentration. All lines exhibited delayed mitochondrial hyperactivity, suggesting potential metabolic compensation in response to sustained stress. ROS measurements revealed oscillatory redox dynamics, characterised by early ROS perturbations followed by significant ROS suppression at later time points, indicating activation of antioxidant responses. Collectively, the data show that cells respond to repeated METH exposure not by undergoing cell death but by adjusting proliferation, mitochondrial function, and redox homeostasis. Chronic methamphetamine exposure alters cancer cell types’ physiology differently through cytostatic, metabolic, and redox adaptation, rather than through direct cytotoxicity. These findings highlight the need for deeper mechanistic studies into how psychostimulant use may influence cancer cell behaviour, metabolic resilience, and stress-response pathways.