Saikosaponin A enhances Docetaxel efficacy by selectively inducing death of dormant prostate cancer cells through excessive autophagy. (1st February 2023)

• Record Type: Journal Article
• Authors: Feng, Jiling; Xi, Zhichao; Jiang, Xue; Li, Yang; Nik Nabil, Wan Najbah; Liu, Mengfan; Song, Zejia; Chen, Xiaoqiong; Zhou, Hua; Dong, Qihan; Xu, Hongxi
• Is Part Of: Cancer letters. Volume 554(2023)
• Publication Date: 2023-02-01
• Subjects: Quiescent cancer cells -- Prostate cancer -- SSA -- Induce autophagy -- Akt; Baf Bafilomycin A1 -- 5-FU Fluorouracil -- LAMP1 Lysosome-associated membrane protein 1 -- LC3 Microtubule- associated protein1 light chain 3 -- p62 SQSTM1/p62 -- PI Propidium iodide -- QCCs Quiescent cancer cells -- rps6 S6 Ribosomal Protein -- SSA Saikosaponin A -- TUNEL TdT-mediated dUTP Nick End Labeling; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2022.216011
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Quiescent cancer cells (QCCs), also known as dormant cancer cells, resist and survive chemo- and radiotherapy, resulting in treatment failure and later cancer recurrence when QCCs resume cell cycle progression. However, drugs selectively targeting QCCs are lacking. Saikosaponin A (SSA) derived from Bupleurum DC., is highly potent in eradicating multidrug-resistant prostate QCCs compared with proliferative prostate cancer cells. By further exacerbating the already increased autophagy through inactivation of Akt-mTOR signaling, SSA triggered cell death in QCCs. Contrarily, inhibition of autophagy or activation of Akt signaling pathway prevented SSA-induced cell death. The multicycle of Docetaxel treatments increased the proportion of QCCs, whereas administering SSA at intervals of Docetaxel treatments aggravated cell death in vitro and led to tumor growth arrest and cell death in vivo . In conclusion, SSA is posed as a novel QCCs-eradicating agent by aggravating autophagy in QCCs. In combination with the current therapy, SSA has potential to improve treatment effectiveness and to prevent cancer recurrence. Highlights: Saikosaponin A induces quiescent cancer cell death by further exacerbating autophagy. Saikosaponin A exacerbates autophagy through inactivation of Akt-mTOR signaling. Saikosaponin A enhances chemotherapeutic efficacy of Docetaxel in vitro and in vivo. Saikosaponin A-induced autophagy is essential for apoptosis occurrence. Saikosaponin A has potential to prevent treatment failure and cancer recurrence.