Liver cancer is one of the most lethal malignancies and is commonly diagnosed as hepatocellular carcinoma (HCC), a tumor type that affects about 90% of patients. Non-alcoholic steatohepatitis (NASH) and obesity are both risk factors for this disease. HCC initiation and progression are deeply linked with changes in the hepatic microenvironment, with cytokines playing key roles. The understanding of the pathogenic pathways that connect these disorders to liver cancer remains poor. However, the inflammasome-mediated cytokines associated with both diseases are central actors in liver cancer progression. The release of the pro-inflammatory cytokines IL-1β and IL-18 during inflammasome activation leads to several detrimental effects on the liver microenvironment. Considering the critical crosstalk between obesity, NASH, and HCC, this review will present the connections of IL-1β and IL-18 from obesity-associated NASH with HCC and will discuss approaches to using these cytokines as therapeutic targets against HCC.

Ovarian cancer remains one of the most lethal gynecologic malignancies due to late diagnosis, limited treatment options, and frequent chemoresistance. Docosahexaenoic acid (DHA), a long-chain omega-3 polyunsaturated fatty acid, has been associated with anti-tumor effects in various cancer models. Here, we investigated the effects of DHA on cell death, oxidative stress, and mitochondrial function in A2780 human ovarian cancer cells. Our data show that DHA decreases cell viability and proliferation in a dose- and time-dependent manner, promoting lytic cell death with increased membrane permeability and LDH release. We identified pyroptosis as the predominant death mechanism, evidenced by caspase-1 activation, pore formation, and mitochondrial dysfunction. DHA treatment rapidly increased intracellular reactive oxygen species (ROS) and mitochondrial superoxide levels, which were essential for both membrane pore formation and the loss of mitochondrial membrane potential. Notably, ROS scavenging with N-acetylcysteine reversed DHA-induced mitochondrial damage and pyroptosis, indicating ROS dependence. Furthermore, DHA reduced mitochondrial content and impaired spare respiratory capacity, suggesting disrupted mitochondrial adaptability. Caspase-1 inhibition restored both mitochondrial integrity and respiratory function, highlighting a mechanistic role for caspase-1 in mediating DHA-induced bioenergetic dysfunction. Collectively, our findings reveal that DHA compromises ovarian cancer cell survival by triggering ROS- and caspase-1-dependent pyroptosis and mitochondrial dysfunction. This study expands the understanding of DHA’s anti-cancer mechanisms and positions it as a promising candidate for adjuvant therapies targeting mitochondrial vulnerabilities and immunogenic cell death pathways in ovarian cancer.