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Cited by 29Seaweed-derived Bioactive CompoundsPhytochemical Studies and BioactivitiesAlgal biology and biofuel production

The DOI matches its Crossref record; 63 of the 65 references it cites were found in a registry or an index.

Enhanced Expression of p53 and Suppression of PI3K/Akt/mTOR by Three Red Sea Algal Extracts: Insights on Their Composition by LC-MS-Based Metabolic Profiling and Molecular Networking

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Fahmy, Nouran M., El-Din, Mariam I. Gamal, Salem, Maha M., Rashedy, Sarah H., Lee, Gyu Sung, Jang, Yoon Seo, Kim, Ki Hyun, Kim, Chung Sub, El-Shazly, Mohamed, Fayez, Shaimaa·2023·Marine Drugs
DOI 10.3390/md21070404PMC PMC10381385
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Abstract

Brown algae comprise up to 2000 species with wide dissemination in temperate zones. A comprehensive untargeted metabolic profiling guided by molecular networking of three uninvestigated Red-Sea-derived brown algae, namely Sirophysalis trinodis, Polycladia myrica, and Turbinaria triquetra, led to the identification of over 115 metabolites categorized as glycerolipids, fatty acids, sterol lipids, sphingolipids, and phospholipids. The three algae exhibited low-to-moderate antioxidant capacity using DPPH and ABTS assays. Preliminary in vitro antiproliferative studies showed that the algal extracts displayed high cytotoxic activity against a panel of cancer cell lines. The most potent activity was recorded against MCF-7 with IC50 values of 51.37 ± 1.19, 63.44 ± 1.13, and 59.70 ± 1.22 µg/mL for S. trinodis, P. myrica, and T. triquetra, respectively. The cytotoxicity of the algae was selective to MCF-7 without showing notable effects on the proliferation of normal human WISH cells. Morphological studies revealed that the algae caused cell shrinkage, increased cellular debris, triggered detachment, cell rounding, and cytoplasmic condensation in MCF-7 cancer cells. Mechanistic investigations using flow cytometry, qPCR, and Western blot showed that the algae induced apoptosis, initiated cell cycle arrest in the sub-G0/G1 phase, and inhibited the proliferation of cancer cells via increasing mRNA and protein expression of p53, while reducing the expression of PI3K, Akt, and mTOR.

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Crossref · 10.3390/md21070404

Cites

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Figures

Figure 1 Classes of metabolites identified in the three Red Sea algal species. The colors in each bar represent the total number of metabolites per algae.
Figure 1 Classes of metabolites identified in the three Red Sea algal species. The colors in each bar represent the total number of metabolites per algae.CC BY · PubMed Central
Figure 2 Distribution of fatty acids in the Red Sea algal extracts.
Figure 2 Distribution of fatty acids in the Red Sea algal extracts.CC BY · PubMed Central
Figure 3 The molecular network of the annotated metabolites in three Red Sea algal samples (established in the negative mode) shows 261 nodes and 22 clusters. The nodes are labeled with their parent masses. Those nodes showing similar parent masses indicate isomerism. The network is displayed as a pie chart to reflect the relative abundance of each ion in the analyzed samples. Turbinaria triquetra is indicated in red, Polycladia myrica in blue and Sirophysalis trinodis in green.
Figure 3 The molecular network of the annotated metabolites in three Red Sea algal samples (established in the negative mode) shows 261 nodes and 22 clusters. The nodes are labeled with their parent masses. Those nodes showing similar parent masses indicate isomerism. The network is displayed as a pie chart to reflect the relative abundance of each ion in the analyzed samples. Turbinaria triquetra is indicated in red, Polycladia myrica in blue and Sirophysalis trinodis in green.CC BY · PubMed Central
Figure 4 Assessment of the free radical scavenging activity of the crude extracts of S. trinodis, P. myrica, and T. triquetra using DPPH (A) and ABTS (B) assays. Results were expressed as mean ± SE, (n = 3).
Figure 4 Assessment of the free radical scavenging activity of the crude extracts of S. trinodis, P. myrica, and T. triquetra using DPPH (A) and ABTS (B) assays. Results were expressed as mean ± SE, (n = 3).CC BY · PubMed Central
Figure 5 Morphological alterations in MCF-7 cells after 48 h of treatment with the three algal extracts at their IC50 concentrations.
Figure 5 Morphological alterations in MCF-7 cells after 48 h of treatment with the three algal extracts at their IC50 concentrations.CC BY · PubMed Central
Figure 6 Analysis of the population of MCF-7 cells at different phases of the cell cycle before and after 48 h of treatment with the three Red Sea algal extracts at their IC50 concentrations. Results are expressed as mean ± SE, (n = 3).
Figure 6 Analysis of the population of MCF-7 cells at different phases of the cell cycle before and after 48 h of treatment with the three Red Sea algal extracts at their IC50 concentrations. Results are expressed as mean ± SE, (n = 3).CC BY · PubMed Central
Figure 7 Relative expression of p53 and PI3K in MCF-7 cell lines before and after 48 h of treatment with the three Red Sea algal extracts at their IC50 concentrations. Results were expressed as mean ± SE, (n = 3). **** p < 0.0001 is considered significant compared with the MCF-7 control untreated cells.
Figure 7 Relative expression of p53 and PI3K in MCF-7 cell lines before and after 48 h of treatment with the three Red Sea algal extracts at their IC50 concentrations. Results were expressed as mean ± SE, (n = 3). **** p < 0.0001 is considered significant compared with the MCF-7 control untreated cells.CC BY · PubMed Central
Figure 8 Western blotting analysis reveals the efficacy of the three algal extracts, in particular S. trinodis, in reducing the levels of phosphorylated Akt and mTOR proteins in MCF-7 cells. Results were expressed as mean ± SE, (n = 3). **** p < 0.0001 is considered significant compared with the MCF-7 control untreated cells. Bands were relatively expressed to β-actin protein (internal control) (Tables S1 and S2) by Western blot analysis.
Figure 8 Western blotting analysis reveals the efficacy of the three algal extracts, in particular S. trinodis, in reducing the levels of phosphorylated Akt and mTOR proteins in MCF-7 cells. Results were expressed as mean ± SE, (n = 3). **** p < 0.0001 is considered significant compared with the MCF-7 control untreated cells. Bands were relatively expressed to β-actin protein (internal control) (Tables S1 and S2) by Western blot analysis.CC BY · PubMed Central

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Citations

Cites

Show all 65 references

Research works printed but not linked: 3

  1. Kharkwal, 2012, Algae as future drugs, Asian J. Pharm. Clin. Res, 5, 1
  2. Lu, W.-Y., Li, H.-J., and Wu, Y.-C. (2023). Marine Biochemistry, CRC Press.
  3. Salem, 2014, Terpenes and sterols composition of marine brown algae Padina pavonica (Dictyotales) and Hormophysa triquetra (Fucales), Int. J. Pharmacogn. Phytochem., 6, 894

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Metadata

Authors
Fahmy, N. M., El-Din, M. I. G., Salem, M. M., Rashedy, S. H., Lee, G. S., Jang, Y. S., Kim, K. H., Kim, C. S., El-Shazly, M., & Fayez, S.
Affiliations
  • Ain Shams University (EG)
  • Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo 11566, Egypt
  • Tanta University (EG)
  • National Institute of Oceanography and Fisheries (EG)
  • Sungkyunkwan University (KR)
Corresponding author
Kim, Chung Sub
ORCID
Venue
Marine Drugs
Publisher
MDPI AG
Published
2023-07-17
Volume
21
Issue
7
Pages
404
ISSN
1660-3397 (ISSN-L)
DOI
10.3390/md21070404
PMC
PMC10381385
OpenAlex
W4384636495
Cited by
28
References
65
Citations by year
2026: 5 · 2025: 10 · 2024: 13
FWCI
5.74
Type
journal article
Language
en
Open access
Licence
Locations
  • Marine Drugs (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Research Foundation (NRF) of Korea (2022R1A6A1A03054419)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Seaweed-derived Bioactive Compounds
  • Physical Sciences › Chemistry › Organic Chemistry › Phytochemical Studies and Bioactivities
  • Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Algal biology and biofuel production
Keywords
algal metabolites, untargeted metabolomics, molecular networking, glycerolipids, sphingolipids, phospholipids, antioxidant activity, antiproliferative activity, MCF-7 cells, apoptosis, cell cycle arrest, p53 expression, PI3K/AKT/mTOR pathway, cytotoxicity
MeSH terms
Chromatography, Liquid, Humans, Signal Transduction, Tumor Suppressor Protein p53, Apoptosis, Indian Ocean, Phosphatidylinositol 3-Kinases, Cell Line, Tumor, Cell Proliferation, Proto-Oncogene Proteins c-akt, Tandem Mass Spectrometry, TOR Serine-Threonine Kinases, MCF-7 Cells

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