Antitumor Effect of Pyrogallol via miR-134 Mediated S Phase Arrest and Inhibition of PI3K/AKT/Skp2/cMyc Signaling in Hepatocellular Carcinoma

Hyojin Ahn,Eunji Im,Dae Young Lee,Sung-Hoon Kim,Hyo-Jung Lee,Ji Hoon Jung

doi:10.3390/ijms20163985

Hyojin Ahn, Eunji Im + Show 4 more

Open Access

https://doi.org/10.3390/ijms20163985

Copy DOI

Abstract

Though Pyrogallol, one of the natural polyphenols, was known to have anti-inflammatory and antitumor effects in breast and colon cancers, the underlying antitumor mechanisms of Pyrogallol, still remain unclear so far. Here, the antitumor mechanisms of Pyrogallol were elucidated in Hep3B and Huh7 hepatocellular carcinoma cells (HCCs). Pyrogallol showed significant cytotoxicity and reduced the number of colonies in Hep3B and Huh7 cells. Interestingly, Pyrogallol induced S-phase arrest and attenuated the protein expression of CyclinD1, Cyclin E, Cyclin A, c-Myc, S-phase kinase-associated protein 2 (Skp2), p-AKT, PI3K, increased the protein expression of p27, and also reduced the fluorescent expression of Cyclin E in Hep3B and Huh7 cells. Furthermore, Pyrogallol disturbed the interaction between Skp2, p27, and c-Myc in Huh7 cells. Notably, Pyrogallol upregulated miRNA levels of miR-134, and conversely, miR-134 inhibition rescued the decreased expression levels of c-Myc, Cyclin E, and Cyclin D1 and increased the expression of p27 by Pyrogallol in Huh7 cells. Taken together, our findings provide insight that Pyrogallol exerts antitumor effects in HCCs via miR-134 activation-mediated S-phase arrest and inhibition of PI3K/AKT/Skp2/cMyc signaling as a potent anticancer candidate.

Highlights

Liver cancer is recognized as the sixth most common cancer and the fourth leading cause of cancer mortality all over the world [1]
Our findings provide insight that Pyrogallol exerts antitumor effects in hepatocellular carcinoma cells (HCCs) via miR-134 activation-mediated S-phase arrest and inhibition of PI3K/AKT/S-phase kinase-associated protein 2 (Skp2)/cMyc signaling as a potent anticancer candidate
The MTT assay revealed that Pyrogallol decreased the viability of Hep3B and Huh7 were conducted

Summary

Introduction

Liver cancer is recognized as the sixth most common cancer and the fourth leading cause of cancer mortality all over the world [1]. Mainly with sorafenib, radiotherapy, surgery, and immunotherapy have been used for the treatment of HCC for years, the therapies are unsatisfactory due to its high recurrence rates and frequent accompanying cirrhosis [3,4]. Combination treatments to overcome resistance to anticancer agents were recommended for effective cancer therapy [5,6]. It is well documented that cell cycle arrest, including G0/G1, S, and G2/M phases are another option regardless of apoptosis induction in cancers [8,9]. Many natural products such as lupeol [10], Biochanin A [11], and sulforaphane [12] are attractive for targeting S-phase arrest

Methods

Results

Discussion

Conclusion