Molecular Mechanisms of the Anti-Cancer Effects of Isothiocyanates from Cruciferous Vegetables in Bladder Cancer

Abstract

Bladder cancer (BC) is a representative of urological cancer with a high recurrence and metastasis potential. Currently, cisplatin-based chemotherapy and immune checkpoint inhibitors are used as standard therapy in patients with advanced/metastatic BC. However, these therapies often show severe adverse events, and prolongation of survival is unsatisfactory. Therefore, a treatment strategy using natural compounds is of great interest. In this review, we focused on the anti-cancer effects of isothiocyanates (ITCs) derived from cruciferous vegetables, which are widely cultivated and consumed in many regions worldwide. Specifically, we discuss the anti-cancer effects of four ITC compounds—allyl isothiocyanate, benzyl isothiocyanate, sulforaphane, and phenethyl isothiocyanate—in BC; the molecular mechanisms underlying their anti-cancer effects; current trends and future direction of ITC-based treatment strategies; and the carcinogenic potential of ITCs. We also discuss the advantages and limitations of each ITC in BC treatment, furthering the consideration of ITCs in treatment strategies and for improving the prognosis of patients with BC.

Bladder Cancer Metastasis Induced by Chronic Everolimus Application Can Be Counteracted by Sulforaphane In Vitro

“…SFN, as one of these natural HDAC inhibitors, has been reported to exert both chemo-preventive and anti-carcinogenic effects on various tumor types [ 13 ]. It is of particular interest that combining HDAC and mTOR inhibitors may not only elicit additive effects but also counteract resistance induction towards an mTOR inhibitor based regimen.…”

Perspective on dietary isothiocyanates in the prevention, development and treatment of cancer

“…These authors have reviewed the molecular mechanisms for individual ITCs and emphasized roles for nuclear factor (erythroid-derived 2)-like 2, (Nrf2) and nuclear factor-kappa beta modulation. In addition, another common and widely studied ITC, allylisothiocyanate (AITC) also possesses anti-inflammatory and antioxidant properties that can improve oxidative stress in pathological processes [32] . Singh et al [30] reviewed the key features of the ITC, erucin (4-methylthio butyl isothiocyanate; 4-MTB-ITC) closely related to SFN, and studied in rodent models of cancer, showing mechanisms of chemopreventive and anticancer effects including apoptosis and cell-cycle arrest, and also enhancing the phase II metabolizing enzymes, suppressing phase I metabolizing enzymes, with enhancement of Nrf-2 that leads to enhanced antioxidant activity.…”

“…The known basic structured compound of the ITC family, SFN, derived through digestion or other means, has been well studied and demonstrated by many groups to possess chemopreventive and ant-tumor activities [25,29,[32][33][34][35][36] . The association with cancer chemoprevention has also been established in animal models and minimally yet in humans [27] .…”

The Potential of Active Metabolites in Cruciferous Vegetables to Inhibit the Growth of Cancer Cells

“…Selain itu, regulasi proliferasi sel, siklus sel, dan apoptosis juga berperan dalam aktivitas kemopreventif yang diinduksi senyawa bioaktif sayuran cruciferous. Proses ini diatur oleh mekanisme kompleks yang melibatkan jalur kaspase dan aktivitas mitokondria (Mastuo et al, 2020).…”