1. Academic Validation
  2. Panobinostat inhibits breast cancer progression via Vps34-mediated exosomal pathway

Panobinostat inhibits breast cancer progression via Vps34-mediated exosomal pathway

  • Hum Cell. 2022 Nov 3. doi: 10.1007/s13577-022-00812-3.
Xuan Wang 1 Xuzhi Yin 2
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Basic Medicine Qingdao University, 308 Ningxia Road, Qingdao, 266071, China. wx105yxz@163.com.
  • 2 Department of Commercial Operation, Akesobio, Guangzhou, 528437, China.
Abstract

Exosomes play crucial roles in intercellular communication, including tumor metastasis. Panobinostat (LBH589), a histone deacetylases (HDAC) inhibitor, is an emerging anti-tumor drug with promising efficacy in Cancer therapy. This study was set out from recent evidence that exosome was a mechanism of intercellular drug transfer with significant pharmacological consequences. It enlightened us LBH589 might regulate tumor growth through exosomal secretion. Here we demonstrated LBH589 induced Autophagy and facilitated secretory Autophagy. Furthermore, LBH589 dose- and time-dependently stimulated exosomal release mediated by Vps34/Rab5C pathway, documented by the ablation of Vps34 and/or Rab5C in breast Cancer cells. Additionally, the findings also presented LBH589 inhibited breast Cancer progression via exosomes. Altogether, we revealed a novel mechanism of LBH589 in exosome-mediated anti-tumor effects in breast Cancer. The schematic diagram of signaling pathways involved in the suppression of breast Cancer progression by LBH589 via exosomes.

Keywords

Breast cancer progression; Exosome; Panobinostat; Secretory autophagy; Vps34.

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