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J Cancer 2024; 15(12):3825-3840. doi:10.7150/jca.95592 This issue Cite

Research Paper

Fluoxetine as a Potential Therapeutic Agent for Inhibiting Melanoma Brain and Lung Metastasis: Induction of Apoptosis, G0/G1 Cell Cycle Arrest, and Disruption of Autophagy Flux

Anqi He1,2,3,4,#, Mengling Wu5,#, Yamin Pu5, Ru Li6, Yiwen Zhang5, Jing He1,4✉, Yong Xia1,4,✉, Yimei Ma2,3,✉

1. Department of Rehabilitation Medicine and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.
2. Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
3. Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.
4. Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, 610041, China.
5. Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
6. Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University /West China School of Nursing, Sichuan University, Chengdu, 610041, China.
#These authors contributed equally to this work.

✉ Corresponding authors: Jing He (hejingedu.cn), Yong Xia (yxia4edu.cn) and Yimei Ma (mayimei90com).

Citation:
He A, Wu M, Pu Y, Li R, Zhang Y, He J, Xia Y, Ma Y. Fluoxetine as a Potential Therapeutic Agent for Inhibiting Melanoma Brain and Lung Metastasis: Induction of Apoptosis, G0/G1 Cell Cycle Arrest, and Disruption of Autophagy Flux. J Cancer 2024; 15(12):3825-3840. doi:10.7150/jca.95592. https://www.jcancer.org/v15p3825.htm
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Abstract

Graphic abstract

Brain metastases and lung metastases are major causes of treatment failure and related mortality in melanoma. Fluoxetine hydrochloride (FXT), a widely-used antidepressant, has emerged as a potential anticancer agent in preclinical studies. Previous research has shown its potential to inhibit melanoma. However, its efficacy and the underlying mechanisms in melanoma metastasis, especially concerning brain metastases and lung metastases, remain underexplored. This study investigates FXT's inhibitory effects on melanoma growth and metastasis to the lung and brain. Employing a combination of in vitro assays, we demonstrate FXT's potent suppression of melanoma growth through induction of intrinsic apoptosis, disruption of autophagic flux, and cell cycle arrest at the G0/G1 phase. In in vivo mouse models, we found that FXT exhibits strong inhibitory activity against melanoma brain metastases and lung metastases. Our findings provide a foundation for future clinical exploration of FXT as a novel treatment strategy for melanoma, underscoring its ability to target both primary and metastatic lesions.

Keywords: Melanoma metastasis, Apoptosis, Autophagy, Cell cycle arrest

Citation styles

APA
He, A., Wu, M., Pu, Y., Li, R., Zhang, Y., He, J., Xia, Y., Ma, Y. (2024). Fluoxetine as a Potential Therapeutic Agent for Inhibiting Melanoma Brain and Lung Metastasis: Induction of Apoptosis, G0/G1 Cell Cycle Arrest, and Disruption of Autophagy Flux. Journal of Cancer, 15(12), 3825-3840. https://doi.org/10.7150/jca.95592.

ACS
He, A.; Wu, M.; Pu, Y.; Li, R.; Zhang, Y.; He, J.; Xia, Y.; Ma, Y. Fluoxetine as a Potential Therapeutic Agent for Inhibiting Melanoma Brain and Lung Metastasis: Induction of Apoptosis, G0/G1 Cell Cycle Arrest, and Disruption of Autophagy Flux. J. Cancer 2024, 15 (12), 3825-3840. DOI: 10.7150/jca.95592.

NLM
He A, Wu M, Pu Y, Li R, Zhang Y, He J, Xia Y, Ma Y. Fluoxetine as a Potential Therapeutic Agent for Inhibiting Melanoma Brain and Lung Metastasis: Induction of Apoptosis, G0/G1 Cell Cycle Arrest, and Disruption of Autophagy Flux. J Cancer 2024; 15(12):3825-3840. doi:10.7150/jca.95592. https://www.jcancer.org/v15p3825.htm

CSE
He A, Wu M, Pu Y, Li R, Zhang Y, He J, Xia Y, Ma Y. 2024. Fluoxetine as a Potential Therapeutic Agent for Inhibiting Melanoma Brain and Lung Metastasis: Induction of Apoptosis, G0/G1 Cell Cycle Arrest, and Disruption of Autophagy Flux. J Cancer. 15(12):3825-3840.

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