Related Experiment Video

Updated: Mar 8, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

14.0K

6BIO Enhances Oligonucleotide Activity in Cells: A Potential Combinatorial Anti-androgen Receptor Therapy in Prostate

Xiaowei Zhang1, Daniela Castanotto2, Sangkil Nam3

  • 1Departments of Medical Oncology and Experimental Therapeutics and Molecular and Cellular Biology, City of Hope Medical Center, Duarte, CA 91010, USA.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|January 28, 2017
PubMed

Insights

A novel small molecule, 6-bromo-indirubin-3'-oxime (6BIO), enhances prostate cancer treatment by improving antisense oligonucleotide (ASO) delivery and downregulating androgen receptor (AR) expression. This offers a new therapeutic strategy for this deadly disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Prostate cancer remains a significant cause of mortality in men, necessitating innovative treatment strategies.
  • Current therapies face challenges, including drug resistance and limited efficacy, highlighting the need for novel approaches.

Purpose of the Study:

  • To identify novel small molecules that can enhance the efficacy of antisense oligonucleotides (ASOs) for prostate cancer treatment.
  • To investigate the potential of 6-bromo-indirubin-3 '-oxime (6BIO) as a single agent or in combination therapy for prostate cancer.

Main Methods:

  • High-throughput small-molecule screening was employed to identify compounds that improve ASO delivery.
  • The effects of 6BIO on androgen receptor (AR) expression, AR signaling, and AR-V7 splice variant levels were assessed in prostate cancer cells.
  • The mechanism of action of 6BIO, including its inhibition of glycogen synthase kinase 3 (GSK-3) isoforms, was investigated.

Main Results:

  • 6-bromo-indirubin-3 '-oxime (6BIO) significantly enhanced the cellular uptake and targeting of ASOs without transfection reagents.
  • 6BIO demonstrated a dual action, downregulating both AR expression and signaling, including the drug-resistance-associated AR-V7 variant.
  • 6BIO inhibited GSK-3α and GSK-3β activity, elucidating its mechanism in enhancing ASO function and repressing AR.

Conclusions:

  • 6BIO is a promising therapeutic agent for prostate cancer, improving ASO delivery and directly targeting AR signaling.
  • The findings support the use of 6BIO as a monotherapy or in combination with ASO-based therapies for prostate cancer treatment.
  • This study provides a strong rationale for further clinical investigation of 6BIO in human prostate cancer.
Keywords:
6-bromo-indirubin-3′-oximeAR-V7ASOGSK-3αGSK-3βLNASSOgymnosislocked nucleic acidphosphorothioate

More Related Videos

Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses08:36

Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses

Published on: October 24, 2019

11.8K
An In Vitro Enzymatic Assay to Measure Transcription Inhibition by GalliumIII and H3 5,10,15-trispentafluorophenylcorroles09:00

An In Vitro Enzymatic Assay to Measure Transcription Inhibition by GalliumIII and H3 5,10,15-trispentafluorophenylcorroles

Published on: March 18, 2015

12.1K

Related Concept Videos

Targeted Cancer Therapies02:57

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...
9.0K
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
4.3K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
60
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.2K
Adrenergic Antagonists: Pharmacological Actions of ɑ-Receptor Blockers01:22

Adrenergic Antagonists: Pharmacological Actions of ɑ-Receptor Blockers

α-Adrenergic antagonists, known as α-blockers, exert their effects by inhibiting α-adrenoceptors, leading to specific physiological actions. α1-blockers and α2-blockers have distinct pharmacological actions and therapeutic applications.
α1-blockers: These drugs inhibit α1-adrenoceptors on smooth muscle cells, resulting in vasodilation. This vasodilation lowers blood pressure, making α1-blockers valuable in treating hypertension. Additionally,...
1.8K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
6.3K