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ABCG2 inhibitor YHO-13351 sensitizes cancer stem/initiating-like side population cells to irinotecan.

Anticancer research (2013-04-09)
Yoshiyuki Shishido, Satoshi Ueno, Ryuta Yamazaki, Masato Nagaoka, Takeshi Matsuzaki
ABSTRACT

The aim of this study was to determine the efficacy of the combination of irinotecan and newly-synthesized ABCG2 (breast cancer-resistant protein) inhibitor YHO-13351 in cancer chemotherapy. Side population (SP) and non-SP cells from the human cervical carcinoma cell line HeLa were isolated by fluorescence-activated cell sorting. The antitumor activity of combination therapy with irinotecan and YHO-13351 was evaluated in xenograft studies in athymic BALB/c nude mice. While SP cells exhibited cancer stem/initiating cell-like properties and low sensitivity to irinotecan-alone, YHO-13351 sensitized them to irinotecan in both in vitro and in vivo studies. YHO-13351 in conjunction with irinotecan reduced the increase of the SP cell ratio in the tumors compared to those observed with treatment with irinotecan-alone. Combination therapy with irinotecan and YHO-13351 would not only accelerate the antitumor effect of this regimen, but also play a crucial role in preventing resistance or relapse.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Acrylonitrile, ≥99%, contains 35-45 ppm monomethyl ether hydroquinone as inhibitor
Sigma-Aldrich
Irinotecan hydrochloride, topoisomerase inhibitor
Sigma-Aldrich
7-Ethyl-10-hydroxycamptothecin, ≥98% (HPLC), powder
Sigma-Aldrich
Acrylonitrile, ≥99%, contains 35-45 ppm monomethyl ether hydroquinone as inhibitor
Supelco
Acrylonitrile, analytical standard
Supelco
Acrylonitrile solution, certified reference material, 5000 μg/mL in methanol