PMID- 37239840
OWN - NLM
STAT- MEDLINE
DCOM- 20230529
LR  - 20230529
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 10
DP  - 2023 May 9
TI  - Natural Gallic Acid and Methyl Gallate Induces Apoptosis in Hela Cells through 
      Regulation of Intrinsic and Extrinsic Protein Expression.
LID - 10.3390/ijms24108495 [doi]
LID - 8495
AB  - Induction of apoptosis is one of the targeted approaches in cancer therapies. As 
      previously reported, natural products can induce apoptosis in in vitro cancer 
      treatments. However, the underlying mechanisms of cancer cell death are poorly 
      understood. The present study aimed to elucidate cell death mechanisms of gallic 
      acid (GA) and methyl gallate (MG) from Quercus infectoria toward human cervical 
      cancer cell lines (HeLa). The antiproliferative activity of GA and MG was 
      characterised by an inhibitory concentration using 50% cell populations (IC(50)) 
      by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. 
      Cervical cancer cells, HeLa, were treated with GA and MG for 72 h and calculated 
      for IC(50) values. The IC(50) concentration of both compounds was used to 
      elucidate the apoptotic mechanism using acridine orange/propidium iodide (AO/PI) 
      staining, cell cycle analysis, the Annexin-V FITC dual staining assay, apoptotic 
      proteins expressions (p53, Bax and Bcl-2) and caspase activation analysis. GA and 
      MG inhibited the growth of HeLa cells with an IC(50) value of 10.00 +/- 0.67 microg/mL 
      and 11.00 +/- 0.58 microg/mL, respectively. AO/PI staining revealed incremental 
      apoptotic cells. Cell cycle analysis revealed an accumulation of cells at the 
      sub-G1 phase. The Annexin-V FITC assay showed that cell populations shifted from 
      the viable to apoptotic quadrant. Moreover, p53 and Bax were upregulated, whereas 
      Bcl-2 was markedly downregulated. Activation of caspase 8 and 9 showed an 
      ultimate apoptotic event in HeLa cells treated with GA and MG. In conclusion, GA 
      and MG significantly inhibited HeLa cell growth through apoptosis induction by 
      the activation of the cell death mechanism via extrinsic and extrinsic pathways.
FAU - Abdullah, Hasmah
AU  - Abdullah H
AUID- ORCID: 0000-0003-2550-0354
AD  - Faculty of Resilience, Rabdan Academy, Al Dhafeer Street, Abu Dhabi 22401, United 
      Arab Emirates.
AD  - School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang 
      Kerian 16150, Kelantan, Malaysia.
FAU - Ismail, Ilyana
AU  - Ismail I
AD  - School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang 
      Kerian 16150, Kelantan, Malaysia.
AD  - Faculty of Health Sciences, Universiti Sultan Zainal Abidin, Gong Badak Campus, 
      Kuala Nerus 21300, Terengganu, Malaysia.
FAU - Suppian, Rapeah
AU  - Suppian R
AD  - School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang 
      Kerian 16150, Kelantan, Malaysia.
FAU - Zakaria, Nor Munirah
AU  - Zakaria NM
AUID- ORCID: 0000-0002-5280-7426
AD  - School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang 
      Kerian 16150, Kelantan, Malaysia.
LA  - eng
PT  - Journal Article
DEP - 20230509
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (bcl-2-Associated X Protein)
RN  - 623D3XG80C (methyl gallate)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 632XD903SP (Gallic Acid)
RN  - 0 (Annexins)
SB  - IM
MH  - Female
MH  - Humans
MH  - HeLa Cells
MH  - bcl-2-Associated X Protein/metabolism
MH  - *Uterine Cervical Neoplasms
MH  - Tumor Suppressor Protein p53
MH  - Fluorescein-5-isothiocyanate
MH  - Apoptosis
MH  - Cell Proliferation
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Gallic Acid/pharmacology
MH  - Annexins
MH  - Cell Line, Tumor
PMC - PMC10218240
OTO - NOTNLM
OT  - apoptosis
OT  - gallic acids
OT  - intrinsic and extrinsic pathways
OT  - methyl gallate
COIS- The authors declare that they have no conflict of interest.
EDAT- 2023/05/27 09:42
MHDA- 2023/05/29 06:42
PMCR- 2023/05/09
CRDT- 2023/05/27 01:13
PHST- 2023/02/17 00:00 [received]
PHST- 2023/03/23 00:00 [revised]
PHST- 2023/04/12 00:00 [accepted]
PHST- 2023/05/29 06:42 [medline]
PHST- 2023/05/27 09:42 [pubmed]
PHST- 2023/05/27 01:13 [entrez]
PHST- 2023/05/09 00:00 [pmc-release]
AID - ijms24108495 [pii]
AID - ijms-24-08495 [pii]
AID - 10.3390/ijms24108495 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 May 9;24(10):8495. doi: 10.3390/ijms24108495.