Combining the platinum chemotherapeutic drug Platinol (cisplatin) with the plant-based compound resveratrol increased cell death of malignant mesothelioma cells grown in the lab, but the effectiveness of the treatment varied between mesothelioma cells derived from different patients.
The study, “Cisplatin and resveratrol induce apoptosis and autophagy following oxidative stress in malignant mesothelioma cells,” published in the journal Food and Chemical Toxicology, demonstrated that the resistance to treatment is in part mediated by a clearance mechanism called autophagy, suggesting that blocking this mechanism could be an effective way to improve mesothelioma treatment.
Mesothelioma cells are known for their resistance to traditional chemotherapy drugs, making treatment challenging. Cancer cells can employ numerous mechanisms in developing resistance to treatment, and mesothelioma cells often use a strategy where programs tell a cell to self-destruct, or are switched off.
Such programmed cell death pathways, known as apoptosis, are used by cells when they become severely damaged as a more controlled way of getting rid of old components. Resveratrol, a compound produced by grapes and other plants as a part of their natural protection against infections, has been shown in earlier studies to trigger self-destruction and slow growth of various types of cancer cells.
When researchers at the Soonchunhyang University in Korea added resveratrol to two different mesothelioma cells, they could observe several signs of activated apoptosis. The research team also noted that the cells started producing more reactive oxygen species — strongly oxidizing compounds — a reaction that could be stopped if they treated the cells with antioxidants before administering resveratrol and Platinol.
Although the combination treatment increased cell death in both mesothelioma cell cultures, the team noted that one of them was less sensitive. Taking a closer look at why that might be, they discovered that the less sensitive cell used a process called autophagy to get rid of resveratrol and cisplatin in the cells.
Autophagy is normally used by cells to get rid of old or faulty components, but researchers know that cancer cells often hijack the system for its own survival processes. The autophagy is also tightly linked to self-destruction mechanisms, and blocking it in these cells made them more sensitive to the treatment, increasing the death of cells by programmed cell death.
“From this perspective, our data provides a rationale for targeting the autophagy regulation as a promising therapeutic strategy in the improvement of clinical outcome for this deadly disease,” the researchers wrote.