PMID- 34238173
OWN - NLM
STAT- MEDLINE
DCOM- 20220428
LR  - 20220428
IS  - 1875-5992 (Electronic)
IS  - 1871-5206 (Linking)
VI  - 22
IP  - 5
DP  - 2022
TI  - Ternary Copper (II) Complex Induced Apoptosis and Cell Cycle Arrest in Colorectal 
      Cancer Cells.
PG  - 999-1011
LID - 10.2174/1871520621666210708100019 [doi]
AB  - BACKGROUND: The lack of specificity, severe side effects, and development of drug 
      resistance have largely limited the use of platinum-based compounds in cancer 
      treatment. Therefore, copper complexes have emerged as potential alternatives to 
      platinum-based compounds. OBJECTIVE: Ternary copper (II) complex incorporated 
      with 1-10-phenanthroline and L-tyrosine was investigated for its anti-cancer 
      effects in HT-29 colorectal cancer cells. METHODS: Cytotoxic effects of ternary 
      copper (II) complex in HT-29 cells was evaluated using MTT assay, Real-Time Cell 
      Analysis (RTCA) and lactate dehydrogenase (LDH) assay. Cell cycle analysis was 
      performed using flow cytometry. Apoptosis induction was studied by Annexin 
      V-FITC/Propidium Iodide (PI) staining and mitochondrial membrane potential 
      analysis (JC-10 staining) using flow cytometry. Intracellular Reactive Oxygen 
      Species (ROS) were detected by DCFH-DA assay. The expression of proteins involved 
      in the apoptotic signalling pathway (p53, caspases, and PARP-1) was evaluated by 
      western blot analysis. RESULTS: Ternary copper (II) complex reduced the cell 
      viability of HT-29 cells in a time- and dose-dependent manner, with IC50 of 2.4 +/- 
      0.4 and 0.8 +/- 0.04 muM at 24 and 48 hours, respectively. Cell cycle analysis 
      demonstrated induction of S-phase cell cycle arrest. Morphological evaluation and 
      Annexin V-FITC/PI flow cytometry analysis confirmed induction of apoptosis that 
      was further supported by cleavage and activation of caspase-8, caspase-9, 
      caspase-3, and PARP- 1. Mutant p53 was also downregulated in a dose-dependent 
      manner. No LDH release, mitochondrial membrane potential disruption, and ROS 
      production were observed. CONCLUSION: Ternary copper (II) complex holds great 
      potential to be developed for colorectal cancer treatment.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Arikrishnan, Sathiavani
AU  - Arikrishnan S
AD  - School of Biosciences, Faculty of Health and Medical Sciences, Taylor\'s 
      University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.
FAU - Loh, Jian Sheng
AU  - Loh JS
AD  - School of Pharmacy, Faculty of Health and Medical Sciences, Taylor\'s University, 
      1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.
FAU - Teo, Xian Wei
AU  - Teo XW
AD  - School of Pharmacy, Faculty of Health and Medical Sciences, Taylor\'s University, 
      1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.
FAU - Bin Norizan, Faris
AU  - Bin Norizan F
AD  - School of Pharmacy, Faculty of Health and Medical Sciences, Taylor\'s University, 
      1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.
FAU - Low, May Lee
AU  - Low ML
AD  - Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical 
      University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, 
      Malaysia.
FAU - Lee, Sau Har
AU  - Lee SH
AD  - School of Biosciences, Faculty of Health and Medical Sciences, Taylor\'s 
      University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.
AD  - Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health & 
      Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, 
      Selangor, Malaysia.
FAU - Foo, Jhi Biau
AU  - Foo JB
AD  - School of Pharmacy, Faculty of Health and Medical Sciences, Taylor\'s University, 
      1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.
AD  - Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health & 
      Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, 
      Selangor, Malaysia.
FAU - Tor, Yin Sim
AU  - Tor YS
AD  - School of Biosciences, Faculty of Health and Medical Sciences, Taylor\'s 
      University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.
AD  - Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health & 
      Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, 
      Selangor, Malaysia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Anticancer Agents Med Chem
JT  - Anti-cancer agents in medicinal chemistry
JID - 101265649
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 789U1901C5 (Copper)
SB  - IM
MH  - Apoptosis
MH  - Cell Cycle
MH  - Cell Cycle Checkpoints
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - *Colorectal Neoplasms/drug therapy/metabolism
MH  - *Copper/pharmacology
MH  - Humans
MH  - Reactive Oxygen Species/metabolism
MH  - Tumor Suppressor Protein p53/metabolism
OTO - NOTNLM
OT  - Copper complex
OT  - apoptosis
OT  - caspase
OT  - cell cycle arrest
OT  - colorectal cancer
OT  - p53
EDAT- 2021/07/10 06:00
MHDA- 2022/04/29 06:00
CRDT- 2021/07/09 05:39
PHST- 2020/12/25 00:00 [received]
PHST- 2021/03/26 00:00 [revised]
PHST- 2021/04/26 00:00 [accepted]
PHST- 2021/07/10 06:00 [pubmed]
PHST- 2022/04/29 06:00 [medline]
PHST- 2021/07/09 05:39 [entrez]
AID - ACAMC-EPUB-116556 [pii]
AID - 10.2174/1871520621666210708100019 [doi]
PST - ppublish
SO  - Anticancer Agents Med Chem. 2022;22(5):999-1011. doi: 
      10.2174/1871520621666210708100019.