Phytochemicals as Chemo-Preventive and Therapeutic Agents Against Bladder Cancer: A Comprehensive Review.

Bladder cancer has a high incidence worldwide and is characterized by a high recurrence rate, metastatic potential, and a significant socioeconomic burden. Conventional treatment modalities usually exhibit serious adverse complications, which also negatively affect patients' quality of life. In the context of exploring new treatment approaches with fewer side effects, the utilization of natural compounds as alternative and/or complementary therapeutic options seems appealing. In the present study, the potential use and effects of various bioactive phytochemicals, including curcumin, resveratrol, epigallocatechin, genistein, and several others, in bladder cancer treatment are thoroughly reviewed. A special focus is given to their potential to beneficially modulate important molecular signaling pathways and mechanisms affecting cell survival, proliferation, migration, and apoptosis, which play a crucial role in the pathogenesis of bladder cancer, such as the PI3K/AKT/mTOR, Ras/Raf/MEK/MAPK, Wnt/β-Catenin, Notch, Hedgehog, Hippo, JAK2/STAT3, and PAF/PAF-receptor pathways. Nevertheless, most studies have been conducted in cell cultures and animal models. Due to differences in genetics and metabolism, more clinical trials are needed to ensure the bio-efficacy of these phytochemicals in humans.