A G-Quadruplex Ligand 3,3′-Diethyloxadicarbocyanine Iodide Induces Mitochondrion-Mediated Apoptosis but Not Decrease of Telomerase Activity in Nasopharyngeal Carcinoma NPC-TW01 Cells

Chung Pin Li, Jen Hsin Huang, Ai Chi Chang, Yi Mei Hung, Chao Hsiung Lin, Yee Chao, Shou Dong Lee, Jacqueline Whang-Peng, Tze Sing Huang

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Purpose. The G-quadruplex ligand 3,3′-diethyloxadicarbocyanine iodide (DODC) was reported to enhance the apoptotic potency of pheochromocytoma PC-12 and leukemia HL-60 cells through the inhibition of telomerase activity. In this study, a mitochondrion-mediated apoptotic pathway was demonstrated as another cytotoxic mechanism for DODC action. Methods. 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) and DNA laddering assays were performed to exhibit the cytotoxicity and apoptosis-inducing activity of DODC. Telomeric repeat amplification protocol (TRAP) assay was used to evaluate the effect of DODC on cellular telomerase. The mitochondrial uptake of probe 3,3′-dihexyloxacarbocyanine iodide was measured by flow cytometry. The mitochondrial proteomes were analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ ionization-time of flight mass spectrometry (MALDI-TOF MS). Western blot analyses were adopted to demonstrate the change of the distribution of mitochondrial proteins. Results. DODC alone was able to induce apoptotic cell death but not decrease of telomerase activity in nasopharyngeal carcinoma NPC-TW01 cells. Instead, we found evidence that DODC significantly affected cellular mitochondria. DODC inhibited the uptake of another mitochondrial probe 3,3′-dihexyloxacarbocyanine iodide. By proteomic comparative analysis, we found that DODC induced the increase of prohibitin level in the mitochondria, indicating the occurrence of mitochondrial perturbation. Moreover, DODC was found to induce the levels of p53 and an 18-kDa truncated Bax on mitochondria, which in turn potentiated the release of cytochrome c for activation of caspases. Conclusions. DODC induces NPC-TW01 cell apoptosis via a mitochondrion-mediated mechanism. This paper demonstrates another cytotoxic mechanism of DODC other than inhibition of telomerase.

Original languageEnglish
Pages (from-to)93-100
Number of pages8
JournalPharmaceutical Research
Volume21
Issue number1
DOIs
Publication statusPublished - Jan 1 2004
Externally publishedYes

Fingerprint

G-Quadruplexes
Mitochondria
Telomerase
Iodides
Apoptosis
Ligands
Nasopharyngeal carcinoma
Assays
Flow cytometry
HL-60 Cells
Mitochondrial Proteins
Electrophoresis, Gel, Two-Dimensional
Pheochromocytoma
Cell death
Proteome
Cytotoxicity
Caspases
Cytochromes c
Electrophoresis
Proteomics

Keywords

  • 3,3′-Diethyloxadicarbocyanine iodide
  • p53
  • Prohibitin
  • tbax

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

A G-Quadruplex Ligand 3,3′-Diethyloxadicarbocyanine Iodide Induces Mitochondrion-Mediated Apoptosis but Not Decrease of Telomerase Activity in Nasopharyngeal Carcinoma NPC-TW01 Cells. / Li, Chung Pin; Huang, Jen Hsin; Chang, Ai Chi; Hung, Yi Mei; Lin, Chao Hsiung; Chao, Yee; Lee, Shou Dong; Whang-Peng, Jacqueline; Huang, Tze Sing.

In: Pharmaceutical Research, Vol. 21, No. 1, 01.01.2004, p. 93-100.

Research output: Contribution to journalArticle

Li, Chung Pin ; Huang, Jen Hsin ; Chang, Ai Chi ; Hung, Yi Mei ; Lin, Chao Hsiung ; Chao, Yee ; Lee, Shou Dong ; Whang-Peng, Jacqueline ; Huang, Tze Sing. / A G-Quadruplex Ligand 3,3′-Diethyloxadicarbocyanine Iodide Induces Mitochondrion-Mediated Apoptosis but Not Decrease of Telomerase Activity in Nasopharyngeal Carcinoma NPC-TW01 Cells. In: Pharmaceutical Research. 2004 ; Vol. 21, No. 1. pp. 93-100.
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abstract = "Purpose. The G-quadruplex ligand 3,3′-diethyloxadicarbocyanine iodide (DODC) was reported to enhance the apoptotic potency of pheochromocytoma PC-12 and leukemia HL-60 cells through the inhibition of telomerase activity. In this study, a mitochondrion-mediated apoptotic pathway was demonstrated as another cytotoxic mechanism for DODC action. Methods. 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) and DNA laddering assays were performed to exhibit the cytotoxicity and apoptosis-inducing activity of DODC. Telomeric repeat amplification protocol (TRAP) assay was used to evaluate the effect of DODC on cellular telomerase. The mitochondrial uptake of probe 3,3′-dihexyloxacarbocyanine iodide was measured by flow cytometry. The mitochondrial proteomes were analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ ionization-time of flight mass spectrometry (MALDI-TOF MS). Western blot analyses were adopted to demonstrate the change of the distribution of mitochondrial proteins. Results. DODC alone was able to induce apoptotic cell death but not decrease of telomerase activity in nasopharyngeal carcinoma NPC-TW01 cells. Instead, we found evidence that DODC significantly affected cellular mitochondria. DODC inhibited the uptake of another mitochondrial probe 3,3′-dihexyloxacarbocyanine iodide. By proteomic comparative analysis, we found that DODC induced the increase of prohibitin level in the mitochondria, indicating the occurrence of mitochondrial perturbation. Moreover, DODC was found to induce the levels of p53 and an 18-kDa truncated Bax on mitochondria, which in turn potentiated the release of cytochrome c for activation of caspases. Conclusions. DODC induces NPC-TW01 cell apoptosis via a mitochondrion-mediated mechanism. This paper demonstrates another cytotoxic mechanism of DODC other than inhibition of telomerase.",
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T1 - A G-Quadruplex Ligand 3,3′-Diethyloxadicarbocyanine Iodide Induces Mitochondrion-Mediated Apoptosis but Not Decrease of Telomerase Activity in Nasopharyngeal Carcinoma NPC-TW01 Cells

AU - Li, Chung Pin

AU - Huang, Jen Hsin

AU - Chang, Ai Chi

AU - Hung, Yi Mei

AU - Lin, Chao Hsiung

AU - Chao, Yee

AU - Lee, Shou Dong

AU - Whang-Peng, Jacqueline

AU - Huang, Tze Sing

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N2 - Purpose. The G-quadruplex ligand 3,3′-diethyloxadicarbocyanine iodide (DODC) was reported to enhance the apoptotic potency of pheochromocytoma PC-12 and leukemia HL-60 cells through the inhibition of telomerase activity. In this study, a mitochondrion-mediated apoptotic pathway was demonstrated as another cytotoxic mechanism for DODC action. Methods. 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) and DNA laddering assays were performed to exhibit the cytotoxicity and apoptosis-inducing activity of DODC. Telomeric repeat amplification protocol (TRAP) assay was used to evaluate the effect of DODC on cellular telomerase. The mitochondrial uptake of probe 3,3′-dihexyloxacarbocyanine iodide was measured by flow cytometry. The mitochondrial proteomes were analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ ionization-time of flight mass spectrometry (MALDI-TOF MS). Western blot analyses were adopted to demonstrate the change of the distribution of mitochondrial proteins. Results. DODC alone was able to induce apoptotic cell death but not decrease of telomerase activity in nasopharyngeal carcinoma NPC-TW01 cells. Instead, we found evidence that DODC significantly affected cellular mitochondria. DODC inhibited the uptake of another mitochondrial probe 3,3′-dihexyloxacarbocyanine iodide. By proteomic comparative analysis, we found that DODC induced the increase of prohibitin level in the mitochondria, indicating the occurrence of mitochondrial perturbation. Moreover, DODC was found to induce the levels of p53 and an 18-kDa truncated Bax on mitochondria, which in turn potentiated the release of cytochrome c for activation of caspases. Conclusions. DODC induces NPC-TW01 cell apoptosis via a mitochondrion-mediated mechanism. This paper demonstrates another cytotoxic mechanism of DODC other than inhibition of telomerase.

AB - Purpose. The G-quadruplex ligand 3,3′-diethyloxadicarbocyanine iodide (DODC) was reported to enhance the apoptotic potency of pheochromocytoma PC-12 and leukemia HL-60 cells through the inhibition of telomerase activity. In this study, a mitochondrion-mediated apoptotic pathway was demonstrated as another cytotoxic mechanism for DODC action. Methods. 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) and DNA laddering assays were performed to exhibit the cytotoxicity and apoptosis-inducing activity of DODC. Telomeric repeat amplification protocol (TRAP) assay was used to evaluate the effect of DODC on cellular telomerase. The mitochondrial uptake of probe 3,3′-dihexyloxacarbocyanine iodide was measured by flow cytometry. The mitochondrial proteomes were analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ ionization-time of flight mass spectrometry (MALDI-TOF MS). Western blot analyses were adopted to demonstrate the change of the distribution of mitochondrial proteins. Results. DODC alone was able to induce apoptotic cell death but not decrease of telomerase activity in nasopharyngeal carcinoma NPC-TW01 cells. Instead, we found evidence that DODC significantly affected cellular mitochondria. DODC inhibited the uptake of another mitochondrial probe 3,3′-dihexyloxacarbocyanine iodide. By proteomic comparative analysis, we found that DODC induced the increase of prohibitin level in the mitochondria, indicating the occurrence of mitochondrial perturbation. Moreover, DODC was found to induce the levels of p53 and an 18-kDa truncated Bax on mitochondria, which in turn potentiated the release of cytochrome c for activation of caspases. Conclusions. DODC induces NPC-TW01 cell apoptosis via a mitochondrion-mediated mechanism. This paper demonstrates another cytotoxic mechanism of DODC other than inhibition of telomerase.

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