AqF026 may act as a cancer therapeutic agent via inducing cancer cell oncosis

Cancer is one of the leading causes of death worldwide, and metastasis is the major cause of death in cancer, therefore, treatments to attenuate metastasis are urgently needed. Cell migration is indispensable in metastatic cascade, and aquaporins (AQPs) promote cell migration by facilitating water influx at cell front (lamellipodia). In fact, AQPs overexpressed widely among many cancer types. Accordingly, previous efforts of targeting AQPs as strategies of cancer treatments were based on AQP inhibitors, yet the efficacy of AQP inhibition was limited based on recent surveys. On the contrary, whether AQP agonist has role in cancer treatments has not been explored. AqF026, an AQP1 agonist, was initially applied to a mouse model of peritoneal dialysis. Herein, we aimed to apply AqF026 to magnify the water influx into lamellipodia of migrating cancer cells so as to induce oncosis by causing overloaded cancer cell swelling in advance of metastatic cascade. Cell swelling is a characteristic of oncosis. With impairment or insufficient regulatory volume decrease (RVD), cell swelling can lead to oncosis. Cancer cells with metastatic potentials shared the same population of cancer cells with multidrug resistance (MDR) lineage, and the impairment or insufficient RVD is shown in cancer cells with MDR. Taken together, the author hypothesized that given appropriate concentration or dose of AQP1 agonist AqF026, the AqF026 may induce oncosis of cancer cells preferentially rather than normal cells by causing overloaded water influx via AQP1 and consequent irreversible cell swelling.