Furowanin A-induced autophagy alleviates apoptosis and promotes cell cycle arrest via inactivation STAT3/Mcl-1 axis in colorectal cancer
Authors: Zhao Ma
Xuebin Bao
Junbao Gu
Journal: Life Sciences (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Apoptosis; Autophagy; Cell cycle arrest; Colorectal cancer; Furowanin A
Affiliations: Gastrointestinal Surgery Department, The People's Hospital of Zhengzhou University (People's Hospital of Henan Province), Zhengzhou, China., Gastrointestinal Surgery Department, The People's Hospital of Zhengzhou University (People's Hospital of Henan Province), Zhengzhou, China. Electronic address: .

Abstract:  Aim Furowanin A (Fur A) is a flavonoid isolated from Millettia pachycarpa Benth. Studies show its potent anti-neoplastic effects against leukemia cells. The aim of the present study was to determine the potential therapeutic effect of Fur A against colorectal cancer (CRC), and elucidate the underlying mechanism. Material and methods: Cell Counting Kit-8 (CCK-8) assay was used to determine cell, and TUNEL and Annexin-V/PI staining was used to detect apoptosis and the cell cycle distribution. The expression levels of specific proteins in the CRC cells were analyzed by Western blotting. A xenograft model was also established to evaluate the therapeutic effect of Fur A in vivo. Key findings: Fur A suppressed proliferation, blocked cell cycle progression, induced apoptosis and promoted autophagy in CRC cells. Interestingly, Fur A-induced autophagy functioned not only as a survival mechanism against apoptosis but also intensified the cell cycle arrest in CRC cells. In addition, Fur A mediated its effects via the inactivation of the STAT3/Mcl-1 axis. Significance: Fur A is a promising drug candidate for the treatment and prevention of CRC. 

Retracted: No

PubPeer comments:
 Fig 12.  H E staining showing minimal effect of Fur A (20 and 40mg kg day) on heart, liver, lung and renal tissues.  Marked up for comparison with this montage I created earlier:  Clockwise from upper left: 6F from [Lin et al (2019)] . 6F [Wang et al (2019)] . 7H [Niu et al (2019)] . 7F [Li et al (2019)] . , 
 Fig 5A:  Autophagy inhibition by 3-MA or si-Beclin 1 augments Fur A-induced apoptosis. Pre-treatment with 3-MA enhanced Fur A-induced apoptosis (A)   All the panels have appeared frequently in Life Sciences, with various labels. Below, for instance, picking an example at random, Fig 5D from [Li et al (2019)] . , 
 Below: Fig 1C :  Fur A inhibits growth of HT29 and SW480 cells. ... C. Fur A inhibited anchorage-independent growth of CRC cells. Middle left, Fig 7E from [Han et al (2016)] :  MiR-370 inhibitor or PIM1 overexpression significantly abrogates the anti-growth effect of AIF . Middle right, 1C from [Xue et al (2019)] ( The effect of PG on colony formation was assessed ). Above, from [Wang et al (2017)] : Figs 1B ( PG suppresses cell proliferation, as determined by colony formation assay ) and 3C ( Ectopic overexpression of PIM1 partly abrogated the anti-proliferative effect of PG both HCC cell lines, as determined by colony formation assay ).  Numerous colony slides in common, differently identified. No authors in common. , 
 *[left]* Fig 8C. *[right]* Fig 8D from  Hispidulin suppresses cell growth and metastasis by targeting PIM1 through JAK2 STAT3 signaling in colorectal cancer ([Liu et al 2018] ) **[retracted]**.  ,