Tocotrienols Modulate Breast Cancer Secretomes and Affect Cancer-Signaling Pathways in MDA-MB-231 Cells: A Label-Free

Premdass Ramdas1,2, Ammu Kutty Radhakrishnan3, Asmahani Azira Abdu Sani4

  • 1Department of Molecular Medicine, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.

Insights

Tocotrienols (T3), a form of vitamin E, show anti-cancer effects by altering protein expression in aggressive breast cancer cells. This study reveals T3

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Tocotrienols (T3), a family of vitamin E, are known for potent anti-cancer properties.
  • The precise molecular mechanisms underlying T3's anti-cancer effects, particularly in aggressive cancer types, require further elucidation.

Purpose of the Study:

  • To investigate the anti-cancer effects of gamma (γ) and delta (δ) Tocotrienols (T3) on MDA-MB-231 human breast cancer cells.
  • To determine the impact of T3 treatment on the secretome profiles of these aggressive, triple-negative breast cancer cells.

Main Methods:

  • MDA-MB-231 cells were treated with varying concentrations of γT3 and δT3.
  • Label-free quantitative proteomic analysis was employed to identify and quantify proteins in the cell culture supernatant.
  • Secretome profiles were analyzed at the half maximal inhibitory concentration (IC50) for both γT3 and δT3.

Main Results:

  • Proteomic analysis identified a significant number of proteins in the cell supernatant.
  • T3 treatment resulted in the differential expression of 18 proteins.
  • Specifically, T3 downregulated Cathepsin D and Serpine1 while upregulating Profilin-1 in MDA-MB-231 cells.

Conclusions:

  • Tocotrienols (T3) modulate the expression of key secreted proteins involved in breast cancer progression.
  • The findings suggest T3 influences cytoskeletal regulation via the RHO GTPase signaling pathway.
  • T3 demonstrates potential as a therapeutic agent against aggressive breast cancers like triple-negative MDA-MB-231 cells.

Related Concept Videos

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...
4.7K
Cancer Survival Analysis01:21

Cancer Survival Analysis

Cancer survival analysis focuses on quantifying and interpreting the time from a key starting point, such as diagnosis or the initiation of treatment, to a specific endpoint, such as remission or death. This analysis provides critical insights into treatment effectiveness and factors that influence patient outcomes, helping to shape clinical decisions and guide prognostic evaluations. A cornerstone of oncology research, survival analysis tackles the challenges of skewed, non-normally...
658
Interactions Between Signaling Pathways01:19

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...
7.3K
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.5K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
9.9K
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
2.9K