Shan Zhu1, Wenhui Jiao1, Yanglu Xu1, Lanjiao Hou1, Hui Li1, Jingrong Shao1, Xiaoliang Zhang1, Ran Wang2, Dexin Kong3. 1. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. 2. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. Electronic address: wangran@tmu.edu.cn. 3. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China; School of Medicine, Tianjin Tianshi College, Tianyuan University, Tianjin 301700, China. Electronic address: kongdexin@tmu.edu.cn.
Abstract
AIMS: Prostate cancer is one of the most frequent causes of cancer death in men worldwide, and novel drugs for prostate cancer therapies are still being developed. Palmitic acid is a common saturated long-chain fatty acid that is known to exhibit anti-inflammatory and metabolic regulatory effects and antitumor activities in several types of tumors. The present study aims to explore the antiproliferative and antimetastatic activities of palmitic acid on human prostate cancer cells and the underlying mechanism. MAIN METHODS: MTT and colony formation assays were utilized to determine the antiproliferative effect of palmitic acid. Cell metastasis was evaluated by wound healing, Transwell migration and invasion assay. The in vivo anticancer effect was assessed by a nude mouse xenograft model of prostate cancer. The involved molecular mechanisms were investigated by flow cytometry and Western blot analysis. KEY FINDINGS: Palmitic acid significantly suppressed prostate cancer cell growth in vitro and in vivo. Treatment with palmitic acid induced G1 phase arrest, which was associated with downregulation of cyclin D1 and p-Rb and upregulation of p27. In addition, palmitic acid could inhibit prostate cancer cell metastasis, in which suppression of PKCζ and p-Integrinβ1 and an increase in E-cadherin expression might be involved. Furthermore, a mechanistic study indicated that palmitic acid inhibited the key molecules of the PI3K/Akt pathway to block prostate cancer proliferation and metastasis. SIGNIFICANCE: Our findings suggested the antitumor potential of palmitic acid for prostate cancer by targeting the PI3K/Akt pathway.
AIMS: Prostate cancer is one of the most frequent causes of cancer death in men worldwide, and novel drugs for prostate cancer therapies are still being developed. Palmitic acid is a common saturated long-chain fatty acid that is known to exhibit anti-inflammatory and metabolic regulatory effects and antitumor activities in several types of tumors. The present study aims to explore the antiproliferative and antimetastatic activities of palmitic acid on human prostate cancer cells and the underlying mechanism. MAIN METHODS: MTT and colony formation assays were utilized to determine the antiproliferative effect of palmitic acid. Cell metastasis was evaluated by wound healing, Transwell migration and invasion assay. The in vivo anticancer effect was assessed by a nude mouse xenograft model of prostate cancer. The involved molecular mechanisms were investigated by flow cytometry and Western blot analysis. KEY FINDINGS: Palmitic acid significantly suppressed prostate cancer cell growth in vitro and in vivo. Treatment with palmitic acid induced G1 phase arrest, which was associated with downregulation of cyclin D1 and p-Rb and upregulation of p27. In addition, palmitic acid could inhibit prostate cancer cell metastasis, in which suppression of PKCζ and p-Integrinβ1 and an increase in E-cadherin expression might be involved. Furthermore, a mechanistic study indicated that palmitic acid inhibited the key molecules of the PI3K/Akt pathway to block prostate cancer proliferation and metastasis. SIGNIFICANCE: Our findings suggested the antitumor potential of palmitic acid for prostate cancer by targeting the PI3K/Akt pathway.