Dicerandrol C Suppresses Proliferation and Induces Apoptosis of HepG2 and Hela Cancer Cells - Inhibiting Wnt/β-Catenin Signaling Pathway

Sep 21, 2026

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Overwhelming evidence indicates abnormal Wnt/β-catenin signaling is central to hepatocellular carcinoma and cervical cancer development. Dicerandrol C (DD-9), a dimeric tetrahydroxanthenone from the endophytic fungus Phomopsis asparagi, was investigated for activity against HepG2 and HeLa cells and its mechanism within the Wnt/β-catenin cascade. DD-9 inhibited proliferation dose- and time-dependently, reduced clonality and metastasis-related behaviors, induced apoptosis, and caused G0/G1 arrest. Mechanistic assays showed β-catenin nuclear translocation blockade and decreased transcription of Wnt target genes and proteins (p-GSK3-β, β-catenin, LEF1, Axin1, c-Myc, CyclinD1), alongside increased GSK3-β and stabilized degradation complex, supported by molecular docking.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Abstract

Introduction

Cancer background and Wnt/β-catenin relevance

Liver cancer (HCC) treatment limitations

Cervical cancer epidemiology and current prevention limits

Materials and Methods

DD-9 isolation and structure elucidation (1D NMR)

Cellular assays (proliferation, clonality, migration, invasion, apoptosis, cell cycle)

Pathway validation (dual luciferase, Western blot, immunofluorescence)

Results

DD-9 suppresses proliferation and induces apoptosis

DD-9 arrests the cell cycle at G0/G1

DD-9 attenuates Wnt/β-catenin signaling and target gene/protein expression

Discussion

Possible DD-9–β-catenin/GSK3-β interaction and mechanistic model

Conclusions

marine drugs Article Dicerandrol C Suppresses Proliferation and Induces Apoptosis of HepG2 and Hela Cancer Cells by Inhibiting Wnt/β-Catenin Signaling Pathway Dongdong Zhou 1,†, Dandan Chen 1,†, Jingwan Wu 1, Ting Feng 1, Pinghuai Liu 1,2 and Jing Xu 1, * Citation: Zhou, D.; Chen, D.; Wu, J.; Feng, T.; Liu, P.; Xu, J. Dicerandrol CSuppresses Proliferation and Induces Apoptosis of HepG2 and Hela Cancer Cells by Inhibiting Wnt/β-Catenin Signaling Pathway. Mar. Drugs 2024, 22, 278. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)md22060278 Academic Editor: Xiaoling Lu Received: 24 May 2024 Revised: 10 June 2024 Accepted: 12 June 2024 Published: 14 June 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Collaborative Innovation Center of Ecological Civilization, School of Chemistry and Chemical Engineering, Hainan University, Haikou 570228, China; [zhoudongdonghf@163.com](zhoudongdonghf@163.com) (D.Z.); [21220856000083@hainanu.edu.cn](21220856000083@hainanu.edu.cn) (D.C.); [20081700110009@hainan.edu.cn](20081700110009@hainan.edu.cn) (J.W.); [20081700210004@hainanu.edu.cn](20081700210004@hainanu.edu.cn) (T.F.); [twlph@163.com](twlph@163.com) (P.L.) 2 Research and Utilization on Seaweed Biological Resources Key Laboratory of Haikou, Haikou 570228, China * [Correspondence: happyjing3@163.com](Correspondence: happyjing3@163.com); Tel.: +86-898-6627-9226 † These authors contributed equally to this work. Abstract: Overwhelming evidence points to an aberrant Wnt/β-catenin signaling as a critical factor in hepatocellular carcinoma (HCC) and cervical cancer (CC) pathogenesis. Dicerandrol C (DD-9), a dimeric tetrahydroxanthenone isolated from the endophytic fungus Phomopsis asparagi DHS-48 obtained from mangrove plant Rhizophora mangle via chemical epigenetic manipulation of the culture, has demonstrated effective anti-tumor properties, with an obscure action mechanism. The objective of the current study was to explore the efficacy of DD-9 on HepG2 and HeLa cancer cells and its functional mechanism amid the Wnt/β catenin signaling cascade. Isolation of DD-9 was carried out using various column chromatographic methods, and its structure was elucidated with 1D NMR. The cytotoxicity of DD-9 on HepG2 and HeLa cells was observed with respect to the proliferation, clonality, migration, invasion, apoptosis, cell cycle, and Wnt/β-catenin signaling cascade. We found that DD-9 treatment significantly reduced tumor cell proliferation in dose-and time-dependent manners in HepG2 and HeLa cells. The subsequent experiments in vitro implied that DD-63 could significantly suppress the tumor clonality, metastases, and induced apoptosis, and that it arrested the cell cycle at the G 0/G1 phase of HepG2 and HeLa cells. Dual luciferase assay, Western blot, and immunofluorescence assay showed that DD-9 could dose-dependently attenuate the Wnt/β-catenin signaling by inhibiting β-catenin transcriptional activity and abrogating β-catenin translocated to the nucleus; down-regulating the transcription level of β-catenin-stimulated Wnt target gene and the expression of related proteins including p-GSK3-β, β-catenin, LEF1, Axin1, c-Myc, and CyclinD1; and up-regulating GSK3-β expression, which indicates that DD-9 stabilized the β-catenin degradation complex, thereby inducing β-catenin degradation and inactivation of the Wnt/β-catenin pathway. The possible interaction between DD-9 and β-catenin and GSK3-β protein was further confirmed by molecular docking studies. Collectively, DD-9 may suppress proliferation and induce apoptosis of liver and cervical cancer cells, possibly at least in part via GSK3-β-m

FAQs

What was the main goal of this study?

To evaluate the anti-cancer efficacy of Dicerandrol C (DD-9) on HepG2 and HeLa cells and determine its functional mechanism within the Wnt/β-catenin signaling pathway.

How was the structure of DD-9 confirmed?

DD-9 was isolated using column chromatographic methods, and its structure was elucidated using 1D NMR.

What effects did DD-9 have on HepG2 and HeLa cancer cells?

DD-9 significantly reduced proliferation in a dose- and time-dependent manner, suppressed clonality and metastasis-related behaviors, induced apoptosis, and arrested the cell cycle at the G0/G1 phase.

How does DD-9 inhibit the Wnt/β-catenin pathway?

DD-9 attenuated Wnt/β-catenin signaling by inhibiting β-catenin transcriptional activity and preventing β-catenin translocation to the nucleus, down-regulating Wnt target genes/proteins while up-regulating GSK3-β to promote β-catenin degradation complex stabilization.

Sep 21, 2026

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