Related Experiment Video
Updated: Nov 24, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Effective ferroptotic small-cell lung cancer cell death from SLC7A11 inhibition by sulforaphane
Yuko Iida1, Mayumi Okamoto-Katsuyama1, Shuichiro Maruoka1
1Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan.
Abstract:
Small-cell lung cancer (SCLC) is a highly aggressive cancer with poor prognosis, due to a lack of therapeutic targets. Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables and has shown anticancer effects against numerous types of cancer. However, its anticancer effect against SCLC remains unclear. The present study aimed to demonstrate the anticancer effects of SFN in SCLC cells by investigating cell death (ferroptosis, necroptosis and caspase inhibition). The human SCLC cell lines NCI-H69, NCI-H69AR (H69AR) and NCI-H82 and the normal bronchial epithelial cell line, 16HBE14o- were used to determine cell growth and cytotoxicity, evaluate the levels of iron and glutathione, and quantify lipid peroxidation following treatment with SFN. mRNA expression levels of cystine/glutamate antiporter xCT (SLC7A11), a key component of the cysteine/glutamate antiporter, were measured using reverse transcription-quantitative PCR, while the levels of SLC7A11 protein were measured using western blot analysis. Following the addition of SFN to the cell culture, cell growth was significantly inhibited, and cell death was shown in SCLC and multidrug-resistant H69AR cells. The ferroptotic effects of SFN were confirmed following culture with the ferroptosis inhibitor, ferrostatin-1, and deferoxamine; iron levels were elevated, which resulted in the accumulation of lipid reactive oxygen species. The mRNA and protein expression levels of SLC7A11 were significantly lower in SFN-treated cells compared with that in the control cells (P<0.0001 and P=0.0006, respectively). These results indicated that the anticancer effects of SFN may be caused by ferroptosis in the SCLC cells, which was hypothesized to be triggered from the inhibition of mRNA and protein expression levels of SLC7A11. In conclusion, the present study demonstrated that SFN-induced cell death was mediated via ferroptosis and inhibition of the mRNA and protein expression levels of SLC7A11 in SCLC cells. The anticancer effects of SFN may provide novel options for SCLC treatment.
Insights
Sulforaphane (SFN) effectively inhibits small-cell lung cancer (SCLC) cell growth by inducing ferroptosis, a type of cell death. This anticancer effect is linked to SFN
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Small-cell lung cancer (SCLC) is an aggressive malignancy with limited therapeutic options.
- Sulforaphane (SFN), a compound from cruciferous vegetables, exhibits anticancer properties but its efficacy in SCLC is not well-defined.
- Investigating novel therapeutic strategies targeting SCLC cell death pathways is crucial.
Purpose of the Study:
- To investigate the anticancer effects of Sulforaphane (SFN) in small-cell lung cancer (SCLC) cells.
- To determine if SFN induces cell death via ferroptosis, necroptosis, or caspase inhibition.
- To elucidate the role of SLC7A11 in SFN-mediated anticancer activity in SCLC.
Main Methods:
- Utilized human SCLC cell lines (NCI-H69, NCI-H69AR, NCI-H82) and a normal bronchial epithelial cell line.
- Assessed cell growth, cytotoxicity, iron levels, glutathione, and lipid peroxidation following SFN treatment.
- Quantified mRNA and protein expression of the cystine/glutamate antiporter xCT (SLC7A11) using RT-qPCR and Western blot.
Main Results:
- SFN significantly inhibited cell growth and induced cell death in SCLC and multidrug-resistant H69AR cells.
- SFN-induced cell death was confirmed as ferroptosis, evidenced by elevated iron levels and lipid peroxidation.
- SFN treatment significantly reduced both mRNA and protein expression levels of SLC7A11.
Conclusions:
- SFN exhibits potent anticancer effects against SCLC cells, primarily through the induction of ferroptosis.
- The mechanism involves the downregulation of SLC7A11 expression at both mRNA and protein levels.
- SFN represents a potential novel therapeutic agent for treating small-cell lung cancer.
