Effects of pretreatment of Hep G2 Cells with β-naphthoflavone on cytotoxicity of propranolol and its active metabolite 4-hydroxypropranolol

Junko Miyano, Harumi Motoyama, Masako Fukuoka, Shigeo Yamamoto, Shizuo Narimatsu, Kenichiro Ogura, Tadashi Watabe, Masuhiro Nishimura, Nobuhiko Ueda, Shinsaku Naito

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Cytotoxicities of propranolol (PL) and its active metabolite, 4-hydroxypropranolol (4-OH-PL), were examined in a human hepatoma cell line, Hep G2. Hep G2 cells were cultured in the presence of β-naphthoflavone (BNF, 25 or 50 μM), lansoprazole (LPZ, 25 or 50 μM) or 0.5% dimethylsulfoxide (vehicle) for 48 hr. The cells were harvested, and microsomal and cytosolic fractions were prepared by differential centrifugation methods. Various enzyme activities were determined as follows: microsomal 7-ethoxyresorufin (ER) O-deethylation as a CYP1A1 index, microsomal phenacetin (PN) O-deethylation as a CYP1A2 index, microsomal and cytosolic p-nitrophenyl acetate (NPA) hydrolysis as a carboxylesterase index and cytosolic 4-OH-PL sulfation as a sulfotransferase index. The pretreatment of Hep G2 cells with LPZ or BNF increased microsomal ER O-deethylase activities, and the potency of BNF was much higher than that of LPZ. Cytosolic 4-OH-PL sulfation was also elevated by the pretreatment with BNF but not with LPZ. Microsomal PN O-deethylase activity was not detectable in either the control or BNF-pretreated group under the conditions used. Microsomal and cytosolic NPA hydrolase activities were similar between the control and the BNF-pretreated groups. Cytotoxicities of PL and 4-OH-PL were attenuated in BNF-pretreated Hep G2 cells compared to non-pretreated Hep G2 cells. These results suggest that increased activities of microsomal CYP1A1 and cytosolic sulfotransferases by pretreatment with BNF may contribute to the attenuating the cytotoxicity of PL and 4-OH-PL in Hep G2 cells, at least in part.

Original languageEnglish
Pages (from-to)292-297
Number of pages6
JournalJournal of Health Science
Volume49
Issue number4
Publication statusPublished - Aug 2003

Fingerprint

Hep G2 Cells
Cytotoxicity
Metabolites
Propranolol
Cytochrome P-450 CYP1A1
Phenacetin
Sulfotransferases
Lansoprazole
Cytochrome P-450 CYP1A2
Carboxylesterase
Centrifugation
4-hydroxypropranolol
Enzyme activity
Hydrolases
Dimethyl Sulfoxide
Hepatocellular Carcinoma
Hydrolysis
Acetates
Cells
hydroxide ion

Keywords

  • β-naphthoflavone
  • 4-hydroxypropranolol
  • Cytotoxicity
  • Hep G2 cell
  • Propranolol
  • Sulfation

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Miyano, J., Motoyama, H., Fukuoka, M., Yamamoto, S., Narimatsu, S., Ogura, K., ... Naito, S. (2003). Effects of pretreatment of Hep G2 Cells with β-naphthoflavone on cytotoxicity of propranolol and its active metabolite 4-hydroxypropranolol. Journal of Health Science, 49(4), 292-297.

Effects of pretreatment of Hep G2 Cells with β-naphthoflavone on cytotoxicity of propranolol and its active metabolite 4-hydroxypropranolol. / Miyano, Junko; Motoyama, Harumi; Fukuoka, Masako; Yamamoto, Shigeo; Narimatsu, Shizuo; Ogura, Kenichiro; Watabe, Tadashi; Nishimura, Masuhiro; Ueda, Nobuhiko; Naito, Shinsaku.

In: Journal of Health Science, Vol. 49, No. 4, 08.2003, p. 292-297.

Research output: Contribution to journalArticle

Miyano, J, Motoyama, H, Fukuoka, M, Yamamoto, S, Narimatsu, S, Ogura, K, Watabe, T, Nishimura, M, Ueda, N & Naito, S 2003, 'Effects of pretreatment of Hep G2 Cells with β-naphthoflavone on cytotoxicity of propranolol and its active metabolite 4-hydroxypropranolol', Journal of Health Science, vol. 49, no. 4, pp. 292-297.
Miyano, Junko ; Motoyama, Harumi ; Fukuoka, Masako ; Yamamoto, Shigeo ; Narimatsu, Shizuo ; Ogura, Kenichiro ; Watabe, Tadashi ; Nishimura, Masuhiro ; Ueda, Nobuhiko ; Naito, Shinsaku. / Effects of pretreatment of Hep G2 Cells with β-naphthoflavone on cytotoxicity of propranolol and its active metabolite 4-hydroxypropranolol. In: Journal of Health Science. 2003 ; Vol. 49, No. 4. pp. 292-297.
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abstract = "Cytotoxicities of propranolol (PL) and its active metabolite, 4-hydroxypropranolol (4-OH-PL), were examined in a human hepatoma cell line, Hep G2. Hep G2 cells were cultured in the presence of β-naphthoflavone (BNF, 25 or 50 μM), lansoprazole (LPZ, 25 or 50 μM) or 0.5{\%} dimethylsulfoxide (vehicle) for 48 hr. The cells were harvested, and microsomal and cytosolic fractions were prepared by differential centrifugation methods. Various enzyme activities were determined as follows: microsomal 7-ethoxyresorufin (ER) O-deethylation as a CYP1A1 index, microsomal phenacetin (PN) O-deethylation as a CYP1A2 index, microsomal and cytosolic p-nitrophenyl acetate (NPA) hydrolysis as a carboxylesterase index and cytosolic 4-OH-PL sulfation as a sulfotransferase index. The pretreatment of Hep G2 cells with LPZ or BNF increased microsomal ER O-deethylase activities, and the potency of BNF was much higher than that of LPZ. Cytosolic 4-OH-PL sulfation was also elevated by the pretreatment with BNF but not with LPZ. Microsomal PN O-deethylase activity was not detectable in either the control or BNF-pretreated group under the conditions used. Microsomal and cytosolic NPA hydrolase activities were similar between the control and the BNF-pretreated groups. Cytotoxicities of PL and 4-OH-PL were attenuated in BNF-pretreated Hep G2 cells compared to non-pretreated Hep G2 cells. These results suggest that increased activities of microsomal CYP1A1 and cytosolic sulfotransferases by pretreatment with BNF may contribute to the attenuating the cytotoxicity of PL and 4-OH-PL in Hep G2 cells, at least in part.",
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AU - Fukuoka, Masako

AU - Yamamoto, Shigeo

AU - Narimatsu, Shizuo

AU - Ogura, Kenichiro

AU - Watabe, Tadashi

AU - Nishimura, Masuhiro

AU - Ueda, Nobuhiko

AU - Naito, Shinsaku

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N2 - Cytotoxicities of propranolol (PL) and its active metabolite, 4-hydroxypropranolol (4-OH-PL), were examined in a human hepatoma cell line, Hep G2. Hep G2 cells were cultured in the presence of β-naphthoflavone (BNF, 25 or 50 μM), lansoprazole (LPZ, 25 or 50 μM) or 0.5% dimethylsulfoxide (vehicle) for 48 hr. The cells were harvested, and microsomal and cytosolic fractions were prepared by differential centrifugation methods. Various enzyme activities were determined as follows: microsomal 7-ethoxyresorufin (ER) O-deethylation as a CYP1A1 index, microsomal phenacetin (PN) O-deethylation as a CYP1A2 index, microsomal and cytosolic p-nitrophenyl acetate (NPA) hydrolysis as a carboxylesterase index and cytosolic 4-OH-PL sulfation as a sulfotransferase index. The pretreatment of Hep G2 cells with LPZ or BNF increased microsomal ER O-deethylase activities, and the potency of BNF was much higher than that of LPZ. Cytosolic 4-OH-PL sulfation was also elevated by the pretreatment with BNF but not with LPZ. Microsomal PN O-deethylase activity was not detectable in either the control or BNF-pretreated group under the conditions used. Microsomal and cytosolic NPA hydrolase activities were similar between the control and the BNF-pretreated groups. Cytotoxicities of PL and 4-OH-PL were attenuated in BNF-pretreated Hep G2 cells compared to non-pretreated Hep G2 cells. These results suggest that increased activities of microsomal CYP1A1 and cytosolic sulfotransferases by pretreatment with BNF may contribute to the attenuating the cytotoxicity of PL and 4-OH-PL in Hep G2 cells, at least in part.

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