Goniothalamin induces apoptosis in vascular smooth muscle cells

Chan Kok Meng, Nor Fadilah Rajab, M. H A Ishak, A. M. Ali, K. Yusoff, L. B. Din, S. H. Inayat-Hussain

Research output: Contribution to journalArticle

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Abstract

Restenosis represents a major impediment to the success of coronary angioplasty. Abnormal proliferation of vascular smooth muscle cells (VSMCs) has been shown to be an important process in the pathogenesis of restenosis. A number of agents, particularly rapamycin and paclitaxel, have been shown to impact on this process. This study was carried out to determine the mechanisms of cytotoxicity of goniothalamin (GN) on VSMCs. Results from MTT cytotoxicity assay showed that the IC50 for GN was 4.4 μg/ml (22 μM), which was lower compared to the clinically used rapamycin (IC50 of 25 μg/ml [27.346 μM]). This was achieved primarily via apoptosis where up to 25.83 ± 0.44% of apoptotic cells were detected after 72 h treatment with GN. In addition, GN demonstrated similar effects as rapamycin in inhibiting VSMCs proliferation using bromodeoxyuridine (BrdU) cell proliferation assay after 72 h treatment at IC50 concentration (p > 0.05). In order to understand the mechanisms of GN, DNA damage detection using comet assay was determined at 2 h post-treatment with GN. Our results showed that there was a concentration-dependent increase in DNA damage in VSMCs prior to cytotoxicity. Moreover, GN effects were comparable to rapamycin. In conclusion, our data show that GN initially induces DNA damage which subsequently leads to cytotoxicity primarily via apoptosis in VSMCs.

Original languageEnglish
Pages (from-to)129-140
Number of pages12
JournalChemico-Biological Interactions
Volume159
Issue number2
DOIs
Publication statusPublished - 1 Feb 2006

Fingerprint

Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Cells
Apoptosis
Sirolimus
Cytotoxicity
Inhibitory Concentration 50
DNA Damage
Assays
Cell proliferation
DNA
Cell Proliferation
Comet Assay
goniothalamin
Damage detection
Bromodeoxyuridine
Paclitaxel
Angioplasty
Therapeutics

Keywords

  • Apoptosis
  • Cytotoxicity
  • DNA damage
  • Goniothalamin
  • VSMCs

ASJC Scopus subject areas

  • Toxicology

Cite this

Kok Meng, C., Rajab, N. F., Ishak, M. H. A., Ali, A. M., Yusoff, K., Din, L. B., & Inayat-Hussain, S. H. (2006). Goniothalamin induces apoptosis in vascular smooth muscle cells. Chemico-Biological Interactions, 159(2), 129-140. https://doi.org/10.1016/j.cbi.2005.10.107

Goniothalamin induces apoptosis in vascular smooth muscle cells. / Kok Meng, Chan; Rajab, Nor Fadilah; Ishak, M. H A; Ali, A. M.; Yusoff, K.; Din, L. B.; Inayat-Hussain, S. H.

In: Chemico-Biological Interactions, Vol. 159, No. 2, 01.02.2006, p. 129-140.

Research output: Contribution to journalArticle

Kok Meng, C, Rajab, NF, Ishak, MHA, Ali, AM, Yusoff, K, Din, LB & Inayat-Hussain, SH 2006, 'Goniothalamin induces apoptosis in vascular smooth muscle cells', Chemico-Biological Interactions, vol. 159, no. 2, pp. 129-140. https://doi.org/10.1016/j.cbi.2005.10.107
Kok Meng, Chan ; Rajab, Nor Fadilah ; Ishak, M. H A ; Ali, A. M. ; Yusoff, K. ; Din, L. B. ; Inayat-Hussain, S. H. / Goniothalamin induces apoptosis in vascular smooth muscle cells. In: Chemico-Biological Interactions. 2006 ; Vol. 159, No. 2. pp. 129-140.
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