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Cited by 57Andrographolide Research and ApplicationsPhytochemistry and Bioactive CompoundsSesquiterpenes and Asteraceae Studies

Andrographolide Exhibits Anticancer Activity against Breast Cancer Cells (MCF-7 and MDA-MB-231 Cells) through Suppressing Cell Proliferation and Inducing Cell Apoptosis via Inactivation of ER-α Receptor and PI3K/AKT/mTOR Signaling

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Tohkayomatee, Ruhainee, Reabroi, Somrudee, Tungmunnithum, Duangjai, Parichatikanond, Warisara, Pinthong, Darawan·2022·Molecules
DOI 10.3390/molecules27113544PMC PMC9182433
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Abstract

Breast cancer is the most common cancer among women worldwide. Chemotherapy followed by endocrine therapy is the standard treatment strategy after surgery or radiotherapy. However, breast cancer is highly resistant to the treatments leading to the recurrence of breast cancer. As a result, the development of alternative medicines derived from natural plants with fewer side effects is being emphasized. Andrographolide isolated from Andrographis paniculata is one of the potential substances with anti-cancer properties in a variety of cell types, including breast cancer cells. This study aims to investigate the anti-cancer effects of andrographolide in breast cancer cells by evaluating cell viability and apoptosis as well as its underlying mechanisms through estrogen receptor (ER)-dependent and PI3K/AKT/mTOR signaling pathways. Cell viability, cell apoptosis, mRNA or miRNA, and protein expression were examined by MTT assay, Annexin V-FITC, qRT-PCR, and Western blot analysis, respectively. MCF-7 and MDA-MB-231 cell viability was reduced in a concentration- and time-dependent manner after andrographolide treatment. Moreover, andrographolide induced cell apoptosis in both MCF-7 and MDA-MB-231 cells by inhibiting Bcl-2 and enhancing Bax expression at both mRNA and protein levels. In MCF-7 cells, the ER-positive breast cancer, andrographolide showed an inhibitory effect on cell proliferation through downregulation of ERα, PI3K, and mTOR expression levels. Andrographolide also inhibited MDA-MB-231 breast cancer cell proliferation via induction of cell apoptosis. However, the inhibition of MCF-7 and MDA-MB-231 cell proliferation of andrographolide treatment did not disrupt miR-21. Our findings showed that andrographolide possesses an anti-estrogenic effect by suppressing cell proliferation in MCF-7 cells. The effects were comparable to those of the anticancer drug fulvestrant in MCF-7 cells. This study provides new insights into the anti-cancer effect of andrographolide on breast cancer and suggests andrographolide as a potential alternative from the natural plant for treating breast cancer types that are resistant to tamoxifen and fulvestrant.

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Authors
Tohkayomatee, R., Reabroi, S., Tungmunnithum, D., Parichatikanond, W., & Pinthong, D.
Affiliations
Mahidol University (TH)
Corresponding author
Pinthong, Darawan
ORCID
Venue
Molecules
Publisher
MDPI AG
Published
2022-05-31
Volume
27
Issue
11
Pages
3544
ISSN
1420-3049 (ISSN-L)
DOI
10.3390/molecules27113544
PMC
PMC9182433
OpenAlex
W4281621835
Cited by
57
References
46
Citations by year
2026: 18 · 2025: 14 · 2024: 12 · 2023: 12 · 2022: 1
FWCI
10.19
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecules (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Ministry of Higher Education, Science, Research, and Innovation
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Andrographolide Research and Applications
  • Physical Sciences › Materials Science › Biomaterials › Phytochemistry and Bioactive Compounds
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Sesquiterpenes and Asteraceae Studies
Keywords
andrographolide, Andrographis paniculata, breast cancer, MCF-7 cells, MDA-MB-231 cells, cell proliferation, apoptosis, estrogen receptor alpha, PI3K/AKT/mTOR pathway, Bcl-2, Bax, miR-21, fulvestrant, tamoxifen resistance
MeSH terms
Fulvestrant, Breast Neoplasms, Diterpenes, Female, Humans, RNA, Messenger, Apoptosis, Phosphatidylinositol 3-Kinases, Cell Line, Tumor, Estrogen Receptor alpha, Cell Proliferation, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases, MCF-7 Cells

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