Inhibiting autophagy enhances sulforaphane-induced apoptosis via targeting NRF2 in esophageal squamous cell carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Cruciferous vegetables contain sulforaphane (SFN), a natural compound with reported anti-tumor properties.
• SFN's induction of autophagy in cancer cells may counteract its therapeutic benefits, a mechanism not fully understood in esophageal squamous cell carcinoma (ESCC).
• ESCC is a prevalent malignancy in North China, necessitating research into effective treatment strategies.

Purpose of the Study:

• To investigate the role and molecular mechanism of SFN-induced autophagy in ESCC.
• To evaluate the impact of autophagy inhibition on ESCC sensitivity to SFN.
• To explore the potential of combining SFN with autophagy inhibitors for enhanced ESCC treatment.

Main Methods:

• Assessed SFN's effects on ESCC cell proliferation, apoptosis (caspase pathway activation), and autophagy.
• Investigated the involvement of the NRF2 pathway in SFN-induced autophagy and anti-tumor effects.
• Utilized chloroquine (CQ) as an autophagy inhibitor to assess its impact on SFN efficacy in vitro and in vivo.

Main Results:

• SFN inhibited ESCC cell proliferation and induced apoptosis via caspase pathway activation.
• SFN activated the NRF2 pathway, leading to autophagy induction, which conferred a protective effect against SFN's anti-tumor actions.
• Combining SFN with CQ neutralized NRF2 activation, enhanced caspase pathway activation, and significantly improved SFN's anti-tumor efficiency in ESCC models.

Conclusions:

• SFN exhibits anti-cancer properties in ESCC but also induces protective autophagy mediated by NRF2 activation.
• Inhibition of autophagy with CQ potentiates the anti-tumor effects of SFN in ESCC.
• This study provides a preclinical basis for developing SFN and its analogs, potentially in combination with autophagy inhibitors, for ESCC treatment.