In a 2019 cell study, the effects of cannabidiol (CBD) on T-cell acute lymphoblastic leukemia (T-ALL) cells were investigated. The study provides insight into the mechanisms through which CBD affects cellular processes in leukemia cells and serves as a basis for further research into the potential therapeutic uses of CBD in cancer treatment.
The research showed that CBD targets the mitochondria, the organelles that produce energy in cells, and alters their ability to handle calcium, resulting in changes to multiple cellular functions such as reactive oxygen species production, metabolic changes, and programmed cell death.
Autophagy and apoptosis are crucial cellular processes that help maintain cellular homeostasis by removing unnecessary or damaged components. While autophagy is a recycling process that breaks down such components, apoptosis is a programmed cell death process that eliminates unwanted cells. CBD has been shown to induce a crosstalk between autophagy and apoptosis in breast cancer, and in this study, researchers examined whether CBD could induce autophagy in T-ALL cells.
The study found that low concentrations of CBD were able to induce autophagy in T-ALL cells, potentially allowing for the removal of damaged organelles and the maintenance of cellular homeostasis, while also inducing cell death via apoptosis. The ability of CBD to induce this crosstalk between autophagy and apoptosis may have important implications for developing new therapeutic strategies for cancer treatment.
Interestingly, the study found that CBD had varying effects on T-ALL cells depending on its concentration. At high concentrations, CBD induced regulated cell death, while at lower concentrations, it induced autophagy and even stimulated cell proliferation. Resting T cells were found to be resistant to CBD, while activated T cells were sensitive, though this population is small in T-ALL patients.
The researchers found that CBD interacts with the voltage-dependent anion channel (VDAC) in the outer mitochondrial membrane, which regulates the permeability of the membrane to calcium ions. CBD appears to promote VDAC closure, causing calcium ions to accumulate in the intermembrane space and ultimately enter the mitochondrial matrix via the mitochondrial calcium uniporter (MCU). This leads to mitochondrial calcium overload and the opening of the mitochondrial permeability transition pore (mPTP), resulting in mitochondrial dysfunction and cell death.
In summary, this study provides valuable insights into the interaction between CBD and mitochondria in T-ALL. The results show that CBD directly targets mitochondria and alters their ability to handle calcium, leading to a cascade of cellular effects such as reactive oxygen species production, Ca2+ signaling, metabolic switch, and the induction of autophagy and cell death. Importantly, the study found that resting T cells, which make up the majority of T lymphocyte populations, were resistant to CBD and retained their ability to antigen activation, suggesting potential safety and selectivity for targeting T-ALL cells.
The study also highlights the possibility of including CBD in chemotherapeutic protocols for T-ALL treatment, given the pivotal role of mitochondria in oncogenic reprogramming. Furthermore, the study demonstrated that low CBD concentrations can stimulate cell proliferation and induce autophagy, which may have therapeutic implications in other contexts. Overall, this study provides a strong foundation for further research on the safety and efficacy of CBD as a potential treatment for T-ALL, and sheds light on the important role of mitochondria in cancer pathophysiology.
Study Title: Cannabidiol directly targets mitochondria and disturbs calcium homeostasis in acute lymphoblastic leukemia
Study Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791884