Basic Investigations
ANTITUMOR EFFECT OF SARCNU IN A 06-METHYLGUANINE-DNA METHYLTRANSFERASE POSITIVE HUMAN GLIOMA XENOGRAFT MODEL
Abstract
Objective: To assess whether novel analogue of
nitrosoureas, 2-chloroethyl-3-sarcosinamide- 1-nitrosourea
(SarCNU), has antitumor effect to 06-methylguanine-DNA
methyltransferase (MGMT) positive tumors in vivo.
Methods: MGMT positive human glioma cell line SF-767
xenografts in nude mice were treated with SarCNU. The
antitumor efficacy of SarCNU was compared with the
results of 1, 3-bis(2-chloroethyl)-l-nitrosourea (BCNU)
treatment with or without 06-benzylguanine (06-BG)
preadministration.
Results: Since the SF-767 is MGMT
strongly positive, BCNU treatment alone did not result in a
satisfactory anticancer effect. As expected, 06-BG by
depleting MGMT activity, significantly enhanced BCNU
antltumor efficacy (P<0.001). More interestingly, SarCNU
treatment alone had a better antitumor effect than 06-BG
pins BCNU treatment (F=51.7, P=0.00036).
Conclusion: Since SarCNU enters cells via extraneuronal monoamine
transporter (EMT), the enhanced antitumor activity of
SarCNU in this MGMT positive human tumor xenograft
model may be due to the presence of EMT in SF-767. SarCNU may be used as an alternative treatment for
MGMT positive tumors, specifically for tumors expressing
EMT.
nitrosoureas, 2-chloroethyl-3-sarcosinamide- 1-nitrosourea
(SarCNU), has antitumor effect to 06-methylguanine-DNA
methyltransferase (MGMT) positive tumors in vivo.
Methods: MGMT positive human glioma cell line SF-767
xenografts in nude mice were treated with SarCNU. The
antitumor efficacy of SarCNU was compared with the
results of 1, 3-bis(2-chloroethyl)-l-nitrosourea (BCNU)
treatment with or without 06-benzylguanine (06-BG)
preadministration.
Results: Since the SF-767 is MGMT
strongly positive, BCNU treatment alone did not result in a
satisfactory anticancer effect. As expected, 06-BG by
depleting MGMT activity, significantly enhanced BCNU
antltumor efficacy (P<0.001). More interestingly, SarCNU
treatment alone had a better antitumor effect than 06-BG
pins BCNU treatment (F=51.7, P=0.00036).
Conclusion: Since SarCNU enters cells via extraneuronal monoamine
transporter (EMT), the enhanced antitumor activity of
SarCNU in this MGMT positive human tumor xenograft
model may be due to the presence of EMT in SF-767. SarCNU may be used as an alternative treatment for
MGMT positive tumors, specifically for tumors expressing
EMT.
