DT-13 Inhibits Proliferation and Metastasis of Human Prostate Cancer Cells Through Blocking PI3K/Akt Pathway
Authors: Yuxu Zhong
Dexin Kong
Meihua Jin
Ran Wang
Zhengming Wang
Xin Peng
Yuling Qiu
Zhe Zhang
Yingying Wang
Shaolu Zhang
Shan Zhu
Yao Liu
Journal: Frontiers in Pharmacology (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: DT-13; PI3K/Akt pathway; anti-metastasis; anti-proliferation; apoptosis
Affiliations: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, China., State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China.

Abstract:  DT-13, a saponin monomer 13 from the dwarf lilyturf tuber, was reported to exhibit anti-inflammatory, hepatoprotective, cardioprotective as well as antitumor activities in a number of tumor cells. Prostate cancer is the second leading cause of cancer death in males, discovery of novel antitumor drug for therapy of prostate cancer is expected. Aiming to evaluate whether DT-13 could become a candidate to treat prostate cancer, we recently investigated the antitumor effect of DT-13 on human prostate cancer cells and the underlying mechanism. DT-13 was found to effectively inhibit proliferation and metastasis of prostate cancer PC3 and DU145 cell lines in a dose-dependent manner. Treatment by DT-13 resulted in a mitochondria-mediated apoptosis, which was accompanied by the chromatin condensation and nuclear shrinkage in the prostate cancer cells. Moreover, DT-13 caused remarkable upregulation of Bax, Bad, Cytochrome C, cleaved -caspase 3, -caspase 9 and -PARP, in contrast to the downregulation of Bcl-2. Nevertheless, no obvious change in intracellular ROS level was observed after DT-13 treatment. We further demonstrated that DT-13 could inhibit PC3 cell metastasis in which suppression of Integrinβ1 and MMP2/9 might be involved. Western blot analysis indicated DT-13 significantly decreased the phosphorylation of PDK1, Akt, mTOR as well as p70S6K, suggesting the pro-apoptotic and anti-metastatic effects of DT-13 on prostate cancer cells might be attributed to the blockade of PI3K/Akt pathway. Collectively, our findings suggest DT-13 is worthy of further investigation as a drug candidate for the treatment of prostate cancer. 

Retracted: No

PubPeer comments:
 Figure 2A appears to have some image overlap issues. Perhaps the authors could explain how the assays were performed and imaged; it is difficult to understand a mistake of this nature. *** ![file] , 
 A user on social media created a visualization of this concern: https: twitter.com kaveh1000 status 1209236046367600643?s=20 Alternatively, hereu2019s a direct link to video: https: m.youtube.com watch?v=K4dA_8wfI2U , 
 Two pairs of images in the supplementary figures look too similar to just co-incidentally resemble one another. Could the authors please check? ![file] ![file] , 
 April 8, 2020 correction In the original article, there was a mistake in Figure 2 as published. The images that represent a minor part of the whole pictures were used in the original published paper. The corrected Figure 2 appears below, with the new images covering over 90% of the whole pictures. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. ![file] ,