A new study from researchers at Khon Kaen University in Thailand has revealed that cannabidiol (CBD) could be a powerful weapon against gemcitabine-resistant cholangiocarcinoma (CCA), a particularly challenging form of bile duct cancer.
Published in the journal BMC Complementary Medicine and Therapies, the study highlights CBD’s potential to overcome drug resistance in CCA through mechanisms involving endoplasmic reticulum (ER) stress, both in laboratory settings and in animal models.
CCA is notoriously difficult to treat, especially when patients develop resistance to gemcitabine, a standard chemotherapy drug. The researchers explored whether CBD, a compound derived from marijuana, could be effective in combating this resistance. The results were compelling, as the study found that CBD not only inhibited the growth of cancer cells but also induced significant levels of apoptosis—programmed cell death—by increasing reactive oxygen species (ROS) production. This led to cell cycle arrest and a marked reduction in tumor size in a mouse model.
The study’s findings were striking. The IC50 values, a measure of a substance’s effectiveness in inhibiting a specific biological function, for CBD on gemcitabine-resistant CCA cells ranged from 19.66 to 21.05 µM, demonstrating its potent effect. CBD significantly suppressed tumor growth in mice, with results supported by molecular analysis showing increased markers of ER stress and apoptosis in treated tumors. “CBD treatment resulted in increased expression of ER stress-associated apoptosis proteins, including p-PERK, BiP, ATF4, CHOP, BAX, and cytochrome c,” the researchers noted in the study.
“In xenografted mouse, CBD significantly suppressed tumors at 10 and 40 mg/kg·Bw (P = 0.0007 and P = 0.0278, respectively), which was supported by an increase in CHOP, but a decrease in PCNA expression in tumor tissues.”
Researchers conclude:
The results suggest that CBD exhibits potent anti-cancer activity against gemcitabine-resistant CCA in vitro and in vivo, in part via ER stress-mediated mechanisms. These results indicate that clinical explorative use of CBD on gemcitabine-resistant CCA patients is warranted.
