3,5-Dibenzyloxy-4'-hydroxystilbene induces early caspase-9 activation during apoptosis in human K562 chronic myelogenous leukemia cells

Haslan Roslie, Chan Kok Meng, Nor Fadilah Rajab, Saraswathi S. Velu, Syed Abd Illah Alyahya Syed Abd Kadir, Irmaizatussyehdany Bunyamin, Jean Frederic Faizal Weber, Noel F. Thomas, Abu Bakar Abdul Majeed, Glenn Myatt, Salmaan Hussain Inayat-Hussain

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

A series of 22 stilbene derivatives based on resveratrol were synthesized incorporating acetoxy-, benzyloxy-, carboxy-, chloro-, hydroxy-and methoxy functional groups. We examined the cytotoxicity of these 22 stilbenes in human K562 chronic myelogenous leukemia cells. Only four compounds were cytotoxic namely 4'-hydroxy-3-methoxystilbene (15), 3'-acetoxy-4-chlorostilbene (19), 4'-hydroxy-3,5-dimethoxystilbene or pterostilbene (3) and 3,5-dibenzyloxy-4'-hydroxystilbene (28) with IC 50s of 78 μM, 38 μM, 67 μM and 19.5 μM respectively. Further apoptosis assessment on the most potent compound, 28, confirmed that the cells underwent apoptosis based on phosphatidylserine externalization and loss of mitochondrial membrane potential. Importantly, we observed a concentration-dependent activation of caspase-9 as early as 2 hr with resultant caspase-3 cleavage in 28-induced apoptosis. Additionally, a structure-activity relationship (SAR) study proposed a possible mechanism of action for compound 28. Taken together, our data suggests that the pro-apoptotic effects of 28 involve the intrinsic mitochondrial pathway characterized by an early activation of caspase-9.

Original languageEnglish
Pages (from-to)13-21
Number of pages9
JournalJournal of Toxicological Sciences
Volume37
Issue number1
DOIs
Publication statusPublished - Feb 2012

Fingerprint

Caspase 9
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Stilbenes
Chemical activation
Apoptosis
Mitochondrial Membrane Potential
Phosphatidylserines
Structure-Activity Relationship
Cytotoxicity
Caspase 3
Functional groups
Derivatives
Membranes
4-hydroxystilbene

Keywords

  • Apoptosis
  • Caspase-3
  • Caspase-9
  • K562 cells
  • Mitochondria
  • Stilbene derivatives

ASJC Scopus subject areas

  • Toxicology

Cite this

3,5-Dibenzyloxy-4'-hydroxystilbene induces early caspase-9 activation during apoptosis in human K562 chronic myelogenous leukemia cells. / Roslie, Haslan; Kok Meng, Chan; Rajab, Nor Fadilah; Velu, Saraswathi S.; Kadir, Syed Abd Illah Alyahya Syed Abd; Bunyamin, Irmaizatussyehdany; Weber, Jean Frederic Faizal; Thomas, Noel F.; Majeed, Abu Bakar Abdul; Myatt, Glenn; Inayat-Hussain, Salmaan Hussain.

In: Journal of Toxicological Sciences, Vol. 37, No. 1, 02.2012, p. 13-21.

Research output: Contribution to journalArticle

Roslie, H, Kok Meng, C, Rajab, NF, Velu, SS, Kadir, SAIASA, Bunyamin, I, Weber, JFF, Thomas, NF, Majeed, ABA, Myatt, G & Inayat-Hussain, SH 2012, '3,5-Dibenzyloxy-4'-hydroxystilbene induces early caspase-9 activation during apoptosis in human K562 chronic myelogenous leukemia cells', Journal of Toxicological Sciences, vol. 37, no. 1, pp. 13-21. https://doi.org/10.2131/jts.37.13
Roslie, Haslan ; Kok Meng, Chan ; Rajab, Nor Fadilah ; Velu, Saraswathi S. ; Kadir, Syed Abd Illah Alyahya Syed Abd ; Bunyamin, Irmaizatussyehdany ; Weber, Jean Frederic Faizal ; Thomas, Noel F. ; Majeed, Abu Bakar Abdul ; Myatt, Glenn ; Inayat-Hussain, Salmaan Hussain. / 3,5-Dibenzyloxy-4'-hydroxystilbene induces early caspase-9 activation during apoptosis in human K562 chronic myelogenous leukemia cells. In: Journal of Toxicological Sciences. 2012 ; Vol. 37, No. 1. pp. 13-21.
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abstract = "A series of 22 stilbene derivatives based on resveratrol were synthesized incorporating acetoxy-, benzyloxy-, carboxy-, chloro-, hydroxy-and methoxy functional groups. We examined the cytotoxicity of these 22 stilbenes in human K562 chronic myelogenous leukemia cells. Only four compounds were cytotoxic namely 4'-hydroxy-3-methoxystilbene (15), 3'-acetoxy-4-chlorostilbene (19), 4'-hydroxy-3,5-dimethoxystilbene or pterostilbene (3) and 3,5-dibenzyloxy-4'-hydroxystilbene (28) with IC 50s of 78 μM, 38 μM, 67 μM and 19.5 μM respectively. Further apoptosis assessment on the most potent compound, 28, confirmed that the cells underwent apoptosis based on phosphatidylserine externalization and loss of mitochondrial membrane potential. Importantly, we observed a concentration-dependent activation of caspase-9 as early as 2 hr with resultant caspase-3 cleavage in 28-induced apoptosis. Additionally, a structure-activity relationship (SAR) study proposed a possible mechanism of action for compound 28. Taken together, our data suggests that the pro-apoptotic effects of 28 involve the intrinsic mitochondrial pathway characterized by an early activation of caspase-9.",
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T1 - 3,5-Dibenzyloxy-4'-hydroxystilbene induces early caspase-9 activation during apoptosis in human K562 chronic myelogenous leukemia cells

AU - Roslie, Haslan

AU - Kok Meng, Chan

AU - Rajab, Nor Fadilah

AU - Velu, Saraswathi S.

AU - Kadir, Syed Abd Illah Alyahya Syed Abd

AU - Bunyamin, Irmaizatussyehdany

AU - Weber, Jean Frederic Faizal

AU - Thomas, Noel F.

AU - Majeed, Abu Bakar Abdul

AU - Myatt, Glenn

AU - Inayat-Hussain, Salmaan Hussain

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N2 - A series of 22 stilbene derivatives based on resveratrol were synthesized incorporating acetoxy-, benzyloxy-, carboxy-, chloro-, hydroxy-and methoxy functional groups. We examined the cytotoxicity of these 22 stilbenes in human K562 chronic myelogenous leukemia cells. Only four compounds were cytotoxic namely 4'-hydroxy-3-methoxystilbene (15), 3'-acetoxy-4-chlorostilbene (19), 4'-hydroxy-3,5-dimethoxystilbene or pterostilbene (3) and 3,5-dibenzyloxy-4'-hydroxystilbene (28) with IC 50s of 78 μM, 38 μM, 67 μM and 19.5 μM respectively. Further apoptosis assessment on the most potent compound, 28, confirmed that the cells underwent apoptosis based on phosphatidylserine externalization and loss of mitochondrial membrane potential. Importantly, we observed a concentration-dependent activation of caspase-9 as early as 2 hr with resultant caspase-3 cleavage in 28-induced apoptosis. Additionally, a structure-activity relationship (SAR) study proposed a possible mechanism of action for compound 28. Taken together, our data suggests that the pro-apoptotic effects of 28 involve the intrinsic mitochondrial pathway characterized by an early activation of caspase-9.

AB - A series of 22 stilbene derivatives based on resveratrol were synthesized incorporating acetoxy-, benzyloxy-, carboxy-, chloro-, hydroxy-and methoxy functional groups. We examined the cytotoxicity of these 22 stilbenes in human K562 chronic myelogenous leukemia cells. Only four compounds were cytotoxic namely 4'-hydroxy-3-methoxystilbene (15), 3'-acetoxy-4-chlorostilbene (19), 4'-hydroxy-3,5-dimethoxystilbene or pterostilbene (3) and 3,5-dibenzyloxy-4'-hydroxystilbene (28) with IC 50s of 78 μM, 38 μM, 67 μM and 19.5 μM respectively. Further apoptosis assessment on the most potent compound, 28, confirmed that the cells underwent apoptosis based on phosphatidylserine externalization and loss of mitochondrial membrane potential. Importantly, we observed a concentration-dependent activation of caspase-9 as early as 2 hr with resultant caspase-3 cleavage in 28-induced apoptosis. Additionally, a structure-activity relationship (SAR) study proposed a possible mechanism of action for compound 28. Taken together, our data suggests that the pro-apoptotic effects of 28 involve the intrinsic mitochondrial pathway characterized by an early activation of caspase-9.

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