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.