Related Experiment Video

Updated: Jul 2, 2025

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
09:29

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model

Published on: March 20, 2020

17.6K

A modified natural small molecule inhibits triple-negative breast cancer growth by interacting with Tubb3

Hongwei Han1, Minkai Yang1, Zhongling Wen1

  • 1State Key Laboratory of Pharmaceutical Biotechnology, Institute of Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing, 210023, China; Co-Innovation Center for Sustainable Forestry in Southern China, MOE Key Laboratory of Forest Genetics and Biotechnology, Nanjing Forestry University, Nanjing, 210037, China.

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
|February 20, 2024
PubMed
Abstract

Insights

A novel shikonin derivative, PMMB276, effectively targets beta-tubulin isotype III (Tubb3) in triple-negative breast cancer (TNBC). This Tubb3 inhibitor suppresses tumor growth and offers a promising new therapeutic avenue for TNBC treatment.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Triple-negative breast cancer (TNBC) lacks targeted therapies and has a poor prognosis, necessitating novel treatment strategies.
  • Beta-tubulin isotype III (Tubb3) is implicated in cancer progression and represents a potential therapeutic target for TNBC.
  • Shikonin, a natural compound, exhibits anti-tumor activity, with potential for enhanced efficacy through structural modification.

Purpose of the Study:

  • To investigate the anti-TNBC effects of a novel shikonin derivative, PMMB276.
  • To elucidate the underlying mechanism of action of PMMB276 in TNBC.

Main Methods:

  • Screening of shikonin analogs to identify PMMB276.
  • Utilized flow cytometry, immunofluorescence, immunoblotting, immunoprecipitation, and siRNA silencing for in vitro analysis.
  • Employed iTRAQ proteomics for target identification and in vivo murine models for efficacy assessment.

Main Results:

  • PMMB276 demonstrated significant anti-TNBC activity by suppressing proliferation, inducing apoptosis, and causing G2/M cell cycle arrest.
  • Tubb3 was identified as the molecular target of PMMB276, with the compound regulating microtubule dynamics.
  • In vivo studies confirmed that PMMB276, by inhibiting Tubb3, reduced tumor growth in a murine model of breast cancer.

Conclusions:

  • PMMB276 exhibits therapeutic potential as a Tubb3 inhibitor for treating triple-negative breast cancer.
  • These findings provide a basis for developing shikonin derivatives as anti-TNBC agents.
Keywords:
ApoptosisCell cycleShikoninTriple negative breast cancerTubb3

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

13.0K
Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment11:13

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

Published on: June 9, 2023

1.5K

Related Concept Videos

Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.0K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K
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...
7.6K
mTOR Signaling and Cancer Progression03:03

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...
3.8K
Inhibition of Cdk Activity02:34

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...
4.8K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K