Inhibiting autophagy enhances anti-cancer properties of sulforaphane

Area of Science:

• Oncology
• Pharmacology
• Cell Biology

Background:

• Bladder cancer (BC) has a poor prognosis due to metastasis.
• Chloroquine (CQ), an antimalarial drug, inhibits BC progression by targeting autophagy.
• The precise mechanisms of CQ's action in BC remain unclear.

Purpose of the Study:

• To elucidate the mechanism of chloroquine's (CQ) effect on bladder cancer (BC) cells.
• To investigate the combined effect of CQ and sulforaphane (SFN) on BC progression.
• To explore the impact on key signaling pathways and cellular functions.

Main Methods:

• Analysis of CQ's effect on BC cell migration and proliferation.
• Assessment of ICAM-1 expression changes induced by CQ.
• Evaluation of SFN's role in modulating CQ's anticancer activity.
• Investigation of AKT/GSK-3β and mTOR/ULK pathway regulation.
• Measurement of mitochondrial membrane potential and ROS levels.

Main Results:

• CQ reduced BC cell migration and proliferation but increased ICAM-1 expression.
• SFN enhanced CQ's anticancer effects by regulating AKT/GSK-3β and mTOR/ULK pathways.
• Combined treatment inhibited autophagy, reduced proliferation, and decreased migration.
• Autophagy pathway modulation affected mitochondrial membrane potential and ROS levels.
• CQ and SFN efficacy varied based on the molecular characteristics of BC cell lines.

Conclusions:

• CQ demonstrates antitumor effects in bladder cancer cells, but can also activate pro-tumor pathways like ICAM-1.
• Combining CQ with SFN synergistically enhances anticancer effects through pathway regulation.
• The molecular basis of BC cell lines influences the response to CQ and SFN, highlighting potential for relapse or resistance.