Researchers have developed a new platinum-based chemotherapy compound that combines cisplatin with cannabidiol (CBD), significantly enhancing its antitumor effects while overcoming drug resistance in cancer cells.
In a study published in the Journal of Inorganic Biochemistry, scientists from Kunming University of Science and Technology and Southeast University synthesized a series of platinum(IV) prodrugs (W1-W6), each axially conjugated with CBD. The most effective of these, known as W5, demonstrated potent activity against both platinum-sensitive and cisplatin-resistant tumor cell lines, especially in lung cancer cells (A549R).
According to the researchers, W5 is reduced within tumor cells by glutathione, releasing active cisplatin (Pt(II)) and CBD. The Pt(II) causes DNA damage and impairs the cancer cell’s repair mechanisms, while CBD triggers mitochondrial dysfunction by increasing the expression of the pro-apoptotic protein Noxa. This dual action leads to elevated levels of oxidative stress, disrupted calcium homeostasis, and ultimately cell death.
W5 was particularly effective in cisplatin-resistant cells, with an IC50 value of 8.53 μM—more than three times stronger than CBD alone. The compound also reduced the expression of antioxidant enzymes such as catalase, SOD2, and SOD3, further amplifying cellular stress.
The study suggests that combining CBD with platinum chemotherapy drugs may be a promising strategy to combat resistance while reducing toxicity. By engaging multiple pathways—DNA damage, mitochondrial dysfunction, and endoplasmic reticulum stress—the W5 compound appears to deliver a powerful, multifaceted attack on cancer cells.
