2. Academic Validation
  3. β-Sitosterol Inhibits Tumor Growth and Amplifies Rituximab Sensitivity through Acid Sphingomyelinase/Ceramide Signaling in Diffuse Large B-Cell Lymphoma

β-Sitosterol Inhibits Tumor Growth and Amplifies Rituximab Sensitivity through Acid Sphingomyelinase/Ceramide Signaling in Diffuse Large B-Cell Lymphoma

  • J Agric Food Chem. 2024 Jul 24;72(29):16177-16190. doi: 10.1021/acs.jafc.4c00014.
Guoping He 1 2,  Minghan Qiu 1 3 4 5,  Zhen Yang 3 6 5,  Ke Zhao 1 3,  Ruxue Liu 7,  Hanwei Mei 7,  Xuanzhu Zhao 7,  Teng Song 1 3 4,  Xiaozhi Liu 8,  Miao Zhang 1 3 5,  Huaqing Wang 1 3 5
Affiliations

Affiliations

  • 1 Department of Oncology, Tianjin Union Medical Center of Nankai University, Tianjin 300121, China.
  • 2 Department of Geriatrics, Binhai New Area Hospital of Traditional Chinese Medicine, Tianjin 300121, China.
  • 3 The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin 300121, China.
  • 4 School of Medicine, Nankai University, 300071 Tianjin, China.
  • 5 Tianjin Cancer Institute of lntegrative Traditional Chinese and Western Medicine, Tianjin 300121, China.
  • 6 Department of Laboratory, Tianjin Union Medical Center of Nankai University, Tianjin 300121, China.
  • 7 College of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300121, China.
  • 8 Tianjin Key Laboratory of Epigenetics for Organ Development in Preterm Infants, The Fifth Central Hospital of Tianjin, Tianjin 300450, China.
PMID: 38991150 DOI: 10.1021/acs.jafc.4c00014
Abstract

Rituximab (RTX) resistance is a notable challenge in treating diffuse large B-cell lymphoma (DLBCL). β-Sitosterol (β-ST) is a plant sterol that has been found in a broad variety of fruits, spices, and medicinal Plants. The antineoplastic properties of β-ST are established in various solid malignancies; however, its effect on DLBCL is uncharted. This study investigates the role of β-ST in DLBCL as well as the underlying mechanisms. Our findings indicated that β-ST impeded DLBCL cell proliferation in a concentration- and time-dependent manner. β-ST appeared to alter sphingolipid metabolism, facilitate acid sphingomyelinase (ASM) translocation to the plasma membrane, augment ceramide platforms through increased ceramide synthesis, and consequently induce Apoptosis in DLBCL cells. Furthermore, we found that RTX initiated both apoptotic and survival pathways in vitro, with the former contingent on the transient activation of the ASM, and β-ST could amplify the anti-DLBCL efficacy of RTX by modulating ASM/Ceramide (Cer) signaling. Collectively, our findings elucidate the mechanistic role of β-ST in DLBCL and underscore its potential in amplifying the antineoplastic efficacy of RTX via ASM activation, proposing a potential avenue to improve the efficacy of RTX therapy.

Keywords

acid sphingomyelinase; ceramide; diffuse large B-cell lymphoma; rituximab; tumor growth; β-sitosterol.

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