Related Experiment Video

Updated: Sep 17, 2025

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

Resveratrol Derivatives Inhibit Pro-survival Akt Signaling Pathway in Lung Cancer

Bhurichaya Innets^1,2,3, Satapat Racha^1,2,4, Zin Zin Ei^1,2

¹Center of Excellence in Cancer Cell and Molecular Biology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.

Anticancer Research

|June 27, 2025

Abstract

Background/Aim:

Akt signaling promotes cancer survival and therapy resistance. This study aimed to modify and improve resveratrol's efficacy by enhancing apoptosis induction in non-small cell lung cancer.

Materials And Methods:

Molecular docking analysis was used to investigate the binding between resveratrol derivatives and the Akt protein. Western blot analysis evaluated the levels of apoptosis markers and signaling proteins.

Results:

Resveratrol derivative, RD4 (4-(3-hydroxy-4-methoxyphenethyl)-2,6-dimethoxyphenol), shows binding potential to the allosteric site of Akt. After treatment of H460 cells with RD4 for 24 h, increased apoptosis and decreased levels of phosphorylated-Akt (p-Akt) protein were observed. Moreover, the levels of pro-apoptotic protein Bax and cleaved PARP were elevated, while those of the anti-apoptotic protein Bcl-2 were decreased. However, RD2 exhibited moderate effects at high concentrations and RD3 elevated p-Akt expression while exhibiting no apoptotic activity.

Conclusion:

RD4 suppresses Akt pathways by binding at the allosteric site of Akt. These findings provide a rationale for the design and optimization of novel Akt targeting agents for non-small cell lung cancer treatment.

Insights

A novel resveratrol derivative, RD4, effectively targets the Akt pathway, inducing apoptosis in non-small cell lung cancer cells. This discovery offers a new strategy for developing targeted cancer therapies.

Area of Science:

Oncology
Molecular Biology
Pharmacology

Background:

Akt signaling is crucial for cancer cell survival and resistance to therapy.
Non-small cell lung cancer (NSCLC) often relies on Akt pathway activation.
Resveratrol derivatives are being explored to enhance anti-cancer efficacy.

Purpose of the Study:

To modify and improve resveratrol's effectiveness in inducing apoptosis.
To investigate novel Akt-targeting agents for NSCLC treatment.
To evaluate the anti-cancer potential of resveratrol derivatives on NSCLC.

Main Methods:

Molecular docking simulations to predict binding interactions with Akt.
Western blot analysis to assess apoptosis markers and signaling proteins.
Treatment of H460 NSCLC cells with resveratrol derivatives.

Main Results:

Resveratrol derivative RD4 demonstrated binding affinity to the allosteric site of Akt.
RD4 treatment increased apoptosis and decreased phosphorylated-Akt (p-Akt) levels in H460 cells.
RD4 modulated the expression of apoptosis-related proteins (Bax, Bcl-2, cleaved PARP).

Conclusions:

RD4 effectively suppresses Akt signaling by binding to its allosteric site.
The findings support the development of RD4 as a potential therapeutic agent for NSCLC.
This study provides a basis for designing optimized Akt inhibitors for cancer treatment.

Read full analysis

Keywords:

Akt targeting apoptosis non-small cell lung cancer resveratrol derivatives

More Related Videos

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Published on: March 30, 2019

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma

Published on: March 3, 2023

Related Concept Videos

mTOR Signaling and Cancer Progression

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...

Interactions Between Signaling Pathways

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...

PI3K/mTOR/AKT Signaling Pathway

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...

The Retinoblastoma Gene

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...

Inhibition of Cdk Activity

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...

Articles linked to this work by shared authors, journal, and citation graph.

A luciferase-based high-throughput three-dimensional tumor spheroid model identifies a renieramycin T derivative with anti-cancer stem cell activity in non-small cell lung cancer.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie·2026

Cypripedin Induces Apoptosis and Synergizes with Bortezomib via ER Stress Mediated Ubiquitination of GRP78 in T-Cell Acute Lymphoblastic Leukemia.

Molecules (Basel, Switzerland)·2026

DH_27, a right-half derivative of renieramycin T, induce apoptosis through inhibition of mTOR signaling for lung cancer suppression.

Scientific reports·2026

Chemosensitizing Effects of Resveratrol Derivatives on p53-dependent Apoptosis Triggered by Cisplatin in Human Lung Cancer Cells.

Anticancer research·2026

Methoxy and Ketone Substitutions of Resveratrol Enhance Its Anticancer Activity by Increasing MEK and ERK Binding Affinity in Colorectal Cancer Cells.

Anticancer research·2026

Targeting mTOR Signaling in Cancer: The Promise of Natural Product-derived Inhibitors.

Anticancer research·2026

See all related articles