2. Academic Validation
  3. Platycodin D induces proliferation inhibition and mitochondrial apoptosis in diffuse large B-cell lymphoma

Platycodin D induces proliferation inhibition and mitochondrial apoptosis in diffuse large B-cell lymphoma

  • Exp Hematol. 2023 Apr 19;S0301-472X(23)00160-1. doi: 10.1016/j.exphem.2023.04.002.
Pu Liu 1,  Mengting Zhao 2,  Ye Lin 2,  Xia Jiang 3,  Tianhao Xia 4,  Youhong Li 3,  Ying Lu 5,  Lei Jiang 6
Affiliations

Affiliations

  • 1 Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
  • 2 Department of Pathology and Pathogenic Biology, and Zhejiang Key Laboratory of Pathophysiology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo, Zhejiang, China.
  • 3 Department of Pathology and Pathogenic Biology, and Zhejiang Key Laboratory of Pathophysiology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo, Zhejiang, China;; Department of Hematology, The Affiliated People's Hospital of Ningbo University, Ningbo, Zhejiang, China.
  • 4 Ningbo Institute of Measurement and Testing (Ningbo Inspection and Testing Center for New Materials), Ningbo, Zhejiang, China.
  • 5 Department of Hematology, The Affiliated People's Hospital of Ningbo University, Ningbo, Zhejiang, China.
  • 6 Department of Pathology and Pathogenic Biology, and Zhejiang Key Laboratory of Pathophysiology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo, Zhejiang, China;; Department of Hematology, The Affiliated People's Hospital of Ningbo University, Ningbo, Zhejiang, China;. Electronic address: jianglei@nbu.edu.cn.
PMID: 37085039 DOI: 10.1016/j.exphem.2023.04.002
Abstract

Patients with diffuse large B-cell lymphoma (DLBCL) have unsatisfactory outcomes especially when relapse occurs after initial chemotherapy. Platycodin D (PD), a triterpenoid saponin isolated from the root of Platycodon grandiflorum (Jacq.) A. DC., has demonstrated potent anti-cancer activities. So far, however, information regarding the effect of PD on malignant lymphoma remains unavailable. In the present study, we showed that PD dose-dependently inhibited the viability of a serial of established DLBCL cell lines representing different molecular subtypes, and their sensitivities to PD were comparable. Mitochondrial dysfunction and subsequent intrinsic Apoptosis were induced by PD, as indicated by the loss of mitochondrial membrane potential and the increase in the percentage of Annexin Ⅴ positive cells. Mechanistically, PD treatment downregulated expression levels of anti-apoptotic proteins including Mcl-1, Bcl-2, and Bcl-xL, while upregulated the expression level of pro-apoptotic protein Bak, followed by the cleavage of PARP. Moreover, PD synergistically enhanced the cytotoxicity of Bcl-2 Inhibitor venetoclax. In a SUDHL-4-derived xenograft mouse model, PD administration significantly constrained the tumor growth without obvious side effects. Therefore, our results provided new insights into the role of PD in lymphoma therapy.

Keywords

Platycodin D; apoptosis; diffuse large B-cell lymphoma; mitochondrial dysfunction; venetoclax.

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