A new experimental treatment combining a chemical found in red wine and a popular chemotherapy drug showed a powerful synergistic effect in targeting pleural mesothelioma cells.
Researchers at Soon Chun Hyang University Hospital Cheonan in South Korea combined the platinum-based chemotherapy drug cisplatin with resveratrol, a natural antioxidant found in wine and red grapes.
The result successfully induced apoptosis, or the process of natural cell death, in malignant mesothelioma cells.
Cisplatin has long been one of the most popular drugs to treat mesothelioma and a variety of other cancers. But like many chemotherapy drugs, cisplatin's efficacy remains limited. Resistance can develop following prolonged cycles or can be present innately in patients.
The resveratrol made mesothelioma cells much more vulnerable to cisplatin, an effect Soon Chun Hyang researchers hope will translate into future treatment options.
Furthermore, the data showed the increased resistance of the cells is related to the activation of self-defensive autophagy, or the destructive mechanism of the cell that disassembles unnecessary or dysfunctional components.
“The molecular basis of the synergistic anti-cancer activities of [cisplatin] and [resveratrol] is not yet understood in detail,” lead investigator Yoon-Jin Lee wrote in the study. “However, emerging studies have revealed that [resveratrol] acts as an excellent candidate for potentiation of platinum treatment in vitro and in vivo.”
Food and Chemical Toxicology, an international journal published for the British Industrial Biological Research Association, announced the study's results in August.
A History of Resveratrol in Cancer Research
The Soonchunhyang research team first studied the mesothelioma-fighting power of resveratrol in 2012 when they found that lab mice exposed to 20 mg/kg of resveratrol daily for four weeks experienced suppressed tumor growth and increased survival.
In 2014, the team uncovered a synergy between resveratrol and the drug clofarabine, which is typically used to treat lymphoblastic leukemia. The combination showed the ability to make mesothelioma cells more vulnerable to chemotherapy.
Those findings, however, were in vitro and far from being substantial enough to reach the clinical trial stage.
The recent study involving cisplatin is another step in the right direction in the exploration of resveratrol's potential role in mesothelioma treatments, especially given the success cisplatin already has as a chemotherapy treatment.
“Escaping from apoptosis is one of cellular adaptation mechanisms that confer malignant cells resistance to anticancer therapies,” Lee wrote. “Therefore, therapeutic interventions targeting apoptotic pathways are considered a useful adjunct to standard cancer therapy and make a signiﬁcant contribution to a favorable treatment outcome.”
While resveratrol is found in red wine, scientists are quick to point out the positive benefits of the compound don't emerge from simply drinking red wine. Our bodies naturally break down the chemical when it enters the body via the digestive system.
Limitations of Cisplatin and Resveratrol
While the cisplatin/resveratrol combination caused cell death in most of the pleural mesothelioma cell lines, one line was more resistant to the treatment.
Instead of causing cell death, the combination triggered the self-defensive mechanism (autophagy) in that particular cell line, causing it to break down and form new malignant cells.
Researchers remedied this by treating the cells with an antibiotic known to inhibit autophagy.
“From this perspective, our data provide a rationale for targeting the autophagy regulation as a promising therapeutic strategy in the improvement of clinical outcome for this deadly disease,” Lee wrote.