Background:
Recent human and animal studies have demonstrated the oncostatic properties
of N-acetyl-5-methoxytryptamine (melatonin) in different types of cancer. However, in few cancer
cell lines including colorectal cancer cell line (HT-29), acute T cell leukemia cell line (JURKAT)
and cervical cancer cell line (HeLa), precise oncostatic mechanism induced by melatonin is yet to be
described.
Objectives:
The aim of this study is to investigate the effects of melatonin in HT-29, JURKAT and
HeLa cells and to determine the underlying molecular mechanism.
Methods:
Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
(MTT) assay while cell cycle, apoptosis and membrane potential were analysed by flow cytometry.
Reactive oxygen species (ROS) was detected by 2',7'.dichlorofluorescein diacetate(DCFH-DA)
staining. Protein expressions were determined by Western blot.
Results:
Our results showed that melatonin suppressed cell proliferation, increased the number of sub
G1 hypodiploid cells and cell cycle arrest in HT-29, JURKAT and HeLa cells. Besides, melatonin also
induced early and late apoptosis, although there were marked variations in responses between different
cell lines (sensitivity; HeLa > HT-29 >JURKAT). Apart from that, staining with DCHF-DA
demonstrated ROS production that was induced in a dose-dependent manner in HeLa, HT-29 and
JURKAT cells. Moreover, the apoptotic process and oncostatic effect of melatonin were seen to be
associated with extracellular-signal-regulated kinase (ERK) and stress-activated protein kinase/c-Jun
NH (2)-terminal kinase (SAPK-JNK) signalling cascades in HeLa cells. In HT-29 and JURKAT cells,
melatonin induced apoptosis via activation of p38 mitogen-activated protein kinases (p38), ERK and
SAPK-JNK signalling pathways. In all three cell lines, the apoptotic event was triggered by the
mammalian target of rapamycin (mTOR)-mediated activation of the downstream target rapamycininsensitive
companion of mTOR (RICTOR) and/or regulatory-associated protein of mTOR (RAPTOR)
proteins.
Conclusions:
Our findings confirm that melatonin induces apoptosis through reactive oxygen speciesmediated
dysregulated mitogen-activated protein kinase (MAPK) and mTOR signalling pathways in
these cancer cell lines.
para‑Phenylenediamine (p‑PD) is a potential carcinogen, and widely used in marketed hair dye formulations. In the present study, the role of the protein tyrosine kinase (PTK)/Ras/Raf/c‑Jun N‑terminal kinase (JNK) and phosphoinositide 3‑kinase (PI3k)/protein kinase B (Akt) pathways on the growth of NRK‑52E cells was investigated. The results demonstrated that p‑PD reduced cell viability in a dose‑dependent manner. The cell death due to apoptosis was confirmed by cell cycle analysis and an Annexin‑V‑fluorescein isothiocyanate binding assay. Subsequent to staining with 2',7'‑dichlorofluorescin diacetate, the treated cells demonstrated a significant increase in reactive oxygen species (ROS) generation compared with the controls. The effects of p‑PD on the signalling pathways were analysed by western blotting. p‑PD‑treated cells exhibited an upregulated phospho‑stress‑activated protein kinase/JNK protein expression level and downregulated Ras and Raf protein expression levels; however, Akt, Bcl‑2, Bcl‑XL and Bad protein expression levels were not significantly altered compared with the control. In conclusion, p‑PD induced apoptosis by a PTK/Ras/Raf/JNK‑dependent pathway and was independent of the PI3K/Akt pathway in NRK‑52E cells.
Introduction: Multitude studies have shown perception is an integral factor associated with smoking, However, no such tool was available in Malay language. In this study, we established a Bahasa Malaysia version of PTSQ (BM-PTSQ) and tested the validity and reliability among secondary school adolescents. Methods: The English version of PTSQ originally consists of 12 items. It was translated into Bahasa Malaysia and back-translated again into English to check for consistency. After face validity (face-to-face query) was determined among 20 secondary school adolescents, only 10 items were included in the survey. Construct validity was established from 407 school adolescents through random selection in the same locality. More than 60% of the respondents were female, a majority (67.3%) were schooling in rural areas. Then, the reliability of the questionnaire was determined with Cronbach’s alpha. Results: EFA has grouped PTSQ into two components, they are associated with either knowledge or attitude towards smoking. The variance and Cronbach’s alpha for the first and second component were 38.24% and 0.861 (7 items) and 21.62% and 0.661 (3 items) respectively. Conclusion: The PTSQ showed good validity and reliability for measurement of perception in smoking among school adolescents in Malaysia, thus this is a viable measurement tool. More importantly this study shows an urgent need to improve the smoking education among adolescents in Malaysia.
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