Antiproliferative and apoptotic activity of glycyrrhizinic acid in MCF-7 human breast cancer cells and evaluation of its effect on cell cycle, cell migration and m-TOR/PI3K/Akt signalling pathway
Authors: Zhen-Yu Li
Zhen Zhang
Yun Feng
Xiao-Zhong Cao
Journal: Archives of Medical Science (2019)
Discipline: CLINICAL MEDICINE
Keywords: apoptosis; breast cancer; cell cycle; flow cytometry; glycyrrhizinic acid.
Affiliations: Departments of General Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan, China.

Abstract:  Introduction: Glycyrrhizinic acid is a natural product of pharmacological relevance and its anticancer activity against breast cancer cell lines has not been evaluated. Therefore the main purpose of the present study was to investigate the anticancer effects of glycyrrhizinic acid in MCF-7 human breast cancer cells. Material and methods: The MTT assay was used to evaluate the anticancer effects while a clonogenic assay was used to study its effects on colony formation tendency. Flow cytometry was used to study the effects on cell cycle phase distribution and apoptosis. Western blot assay was used to study changes in protein expression of the m-TOR/PI3K/Akt pathway. Results: The results indicated that glycyrrhizinic acid caused significant (p &lt; 0.01). The growth inhibitory effects MCF-7 human breast cancer cells. The growth inhibitory effects of glycyrrhizinic acid exhibited concentration-dependent as well as time-dependent growth inhibitory trend. Different doses of glycyrrhizinic acid had a tendency to significantly (p &lt; 0.01) inhibit the colony formation tendency of MCF-7 cells. As compared to the control group, glycyrrhizinic acid-treated cells showed a high percentage of apoptotic cells. Cells treated with a 10, 50 and 100 ¬µM dose of glycyrrhizinic acid led to a 24.3%, 41.5% and 82.1% increase in the sub-G1 phase (apoptotic) cells. Glycyrrhizinic acid also led to significant (p &lt; 0.01) inhibition of cell invasion along with downregulation of m-TOR/PI3K/Akt protein expression. Conclusions: Glycyrrhizinic acid inhibited MCF-7 human breast cancer cell growth and therefore may prove essential lead molecule in the treatment of breast cancer. 

Retracted: No

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 Figure 5  Sub-G1 cell cycle arrest induced by glycyrrhizinic acid in MCF-7 human breast cancer cells. The cells were treated with 0 (A), 10 (B), 50 (C) and 100 (D) u00b5M doses of glycyrrhizinic acid for 48 h, stained with PI and then examined by flow cytometry . These overhangs and repetitive spikes would belong as part of the fortifications of Isengard or Barad-Du00fbr, but they are not really part of a well-ordered cell-count histogram.  , 
 Fig 4C,D.  Glycyrrhizinic acid led to apoptosis induction in MCF-7 human breast cancer cells. The cells were treated with 0 (A), 10 (B), 50 (C) and 100 (D) u00b5M doses of glycyrrhizinic acid for 48 h. The cells were stained with Annexin V-FITC (20 u00b5g ml) and PI (20 u00b5g ml) in the dark. Finally cells were analysed by a FACSCalibur flow cytometer  Repeated area marked. The repetition can also be visualised as the area of cancellation when (D) is color-reversed and superimposed upon (C)  , 
  Figure 6. A u2013 Glycyrrhizinic acid led to inhibition of cell invasion in MCF-7 human breast cancer cells. The cells were treated with 0 (a), 10 (b), 50 (c) and **100 u00b5M (d)** doses of glycyrrhizinic acid for 48 h.  The sharp-edged purplish rectangles around the invading cells are more evident at increased contrast (right). It is as if they were copy-pasted from a different image onto a blank Transwell filter. ,