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Related Concept Videos

Gap Junctions01:37

Gap Junctions

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Multicellular organisms employ a variety of ways for cells to communicate with each other. Gap junctions are specialized proteins that form pores between neighboring cells in animals, connecting the cytoplasm between the two, and allowing for the exchange of molecules and ions. They are found in a wide range of invertebrate and vertebrate species, mediate numerous functions including cell differentiation and development, and are associated with numerous human diseases, including cardiac and...
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Gap Junctions01:27

Gap Junctions

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The cytoplasm of adjacent animal cells can exchange small molecules, ions, and secondary messengers via the communication channels which form the gap junctions. These junctions comprise a few hundred to thousands of molecular channels, each made of two halves, called the connexon hemichannel. A connexon is a hexamer of six transmembrane connexin proteins, which assemble radially, thus forming a pore or channel in the center. One connexon hemichannel docks with a corresponding connexon on the...
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Contact-dependent Signaling01:19

Contact-dependent Signaling

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Contact-dependent signaling, as the name suggests, requires that communicating cells be in direct contact with each other. This is achieved either through receptor-ligand interactions or by specialized cytoplasmic channels that allow the flow of small molecules between cells. In animal cells, channels called gap junctions facilitate contact-dependent signaling in certain tissues, whereas, plasmodesmata perform a similar function in plants.
Gap Junctions
In animal cells, gap junctions are formed...
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Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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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...
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Cancer Therapies02:49

Cancer Therapies

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Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
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Overview of Cell-Matrix Interactions01:24

Overview of Cell-Matrix Interactions

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The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
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Related Experiment Video

Updated: Dec 5, 2025

Gap Junctional Intercellular Communication: A Functional Biomarker to Assess Adverse Effects of Toxicants and Toxins, and Health Benefits of Natural Products
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Gap Junctional Intercellular Communication: A Functional Biomarker to Assess Adverse Effects of Toxicants and Toxins, and Health Benefits of Natural Products

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Modifying gap junction communication in cancer therapy.

Ujjwala M Warawdekar1, Vaishali Jain2, Himani Patel2

  • 1CRI Lab 1, Advanced Centre for Treatment, Research & Education in Cancer, Tata Memorial Centre, Navi Mumbai, India; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400085, India.

Current Research in Translational Medicine
|October 18, 2020
PubMed
Summary

Histone deacetylase inhibitors (HDACi) and All Trans Retinoic Acid (ATRA) enhance gap junction intercellular communication (GJIC) for improved drug delivery. Combining these with Dexamethasone (DXM) overcomes DXM

Keywords:
ATRAConnexinsDexamethasone in prodrug activation therapyHDAC inhibitorsProdrug activation therapy

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A Functional Assay for Gap Junctional Examination; Electroporation of Adherent Cells on Indium-Tin Oxide
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Area of Science:

  • Cancer Biology
  • Molecular Oncology
  • Drug Discovery

Background:

  • Gap junction intercellular communication (GJIC) is vital for drug delivery in tumors.
  • Pro-drug activation therapy, like Ganciclovir triphosphate (GCV-TP), leads to cancer cell death.
  • Histone deacetylase inhibitors (HDACi) and All Trans Retinoic Acid (ATRA) can modulate GJIC.

Purpose of the Study:

  • To enhance GJIC using HDACi and ATRA for improved drug delivery.
  • To investigate the combined effects of HDACi, ATRA, and Dexamethasone (DXM) on GJIC and cancer cell cytotoxicity.
  • To abrogate the detrimental effects of DXM on GJIC when used in combination therapy.

Main Methods:

  • Utilized NT8E and HeLa cell lines, treated with Valproic Acid (VPA), 4 Phenylbutyrate (4PB), ATRA, and DXM.
  • Assessed Connexin (CX 43, 26, 32) and E-Cadherin expression via Western blotting and qRT-PCR.
  • Evaluated GJIC competence, cytotoxicity, and cell death mechanisms in vitro.

Main Results:

  • HDACi (VPA, 4PB) and ATRA significantly enhanced GJIC (30-54%) and increased cytotoxicity (60%).
  • Connexin and E-Cadherin expression patterns were modulated by HDACi, DXM, and ATRA.
  • Combination therapy abrogated DXM's inhibitory effect on GJIC when combined with VPA or ATRA.

Conclusions:

  • Enhanced GJIC via HDACi and ATRA boosts anti-cancer cytotoxicity.
  • Combination therapy with ATRA or VPA can overcome DXM-induced inhibition of GJIC.
  • This strategy holds potential for improving pro-drug activation therapies in cancer treatment.