Interaction of Anticancer Drugs with Human Organic Anion Transporter hOAT4

<div>Dixon plot analysis of the inhibitory effects of epirubicin hydrochloride and dabrafenib mesylate on hOAT4-mediated transport in COS-7 cells. 1.2 <i>μ</i>M and 2.4 <i>μ</i>M [<sup>3</sup>H]-ES uptake was determined at 4 mins in the absence or presence of varying concentrations of epirubicin hydrochloride (a) or dabrafenib mesylate (b). Each data point represents only carrier-mediated transport after subtraction of values from parental cells. Results shown are means ± SE (n=3). The data was fitted by linear regression and <svg height="11.5695pt" id="M10" style="vertical-align:-3.18152pt" version="1.1" viewbox="-0.0498162 -8.38798 11.8914 11.5695" width="11.8914pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M667 0V28C619 34 599 43 546 100C496 154 386 277 311 372C378 440 449 512 488 547C551 605 575 615 650 622V650H410V622L433 619C478 614 479 604 449 568C404 513 337 443 282 390C254 364 234 350 212 345V520C212 609 222 616 299 622V650H41V622C120 616 128 611 128 520V128C128 41 120 34 44 28V0H304V28C221 34 212 41 212 128V318C229 321 242 318 266 291C355 185 436 87 514 0H667Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,8.749,3.132)"><path d="M138 535C169 535 191 560 191 589C191 620 168 644 139 644S85 620 85 589C85 560 110 535 138 535ZM257 0V30C192 35 185 43 185 109V453C142 435 94 422 40 414V386C101 378 104 372 104 311V109C104 41 97 35 33 30V0H257Z"></path></g></svg> was calculated. For epirubicin hydrochloride, <svg height="11.5695pt" id="M11" style="vertical-align:-3.18152pt" version="1.1" viewbox="-0.0498162 -8.38798 11.8914 11.5695" width="11.8914pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M667 0V28C619 34 599 43 546 100C496 154 386 277 311 372C378 440 449 512 488 547C551 605 575 615 650 622V650H410V622L433 619C478 614 479 604 449 568C404 513 337 443 282 390C254 364 234 350 212 345V520C212 609 222 616 299 622V650H41V622C120 616 128 611 128 520V128C128 41 120 34 44 28V0H304V28C221 34 212 41 212 128V318C229 321 242 318 266 291C355 185 436 87 514 0H667Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,8.749,3.132)"><path d="M138 535C169 535 191 560 191 589C191 620 168 644 139 644S85 620 85 589C85 560 110 535 138 535ZM257 0V30C192 35 185 43 185 109V453C142 435 94 422 40 414V386C101 378 104 372 104 311V109C104 41 97 35 33 30V0H257Z"></path></g></svg>= 3 <i>μ</i>M and intersection is (-3, 0); for dabrafenib mesylate, <svg height="11.5695pt" id="M12" style="vertical-align:-3.18152pt" version="1.1" viewbox="-0.0498162 -8.38798 11.8914 11.5695" width="11.8914pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M667 0V28C619 34 599 43 546 100C496 154 386 277 311 372C378 440 449 512 488 547C551 605 575 615 650 622V650H410V622L433 619C478 614 479 604 449 568C404 513 337 443 282 390C254 364 234 350 212 345V520C212 609 222 616 299 622V650H41V622C120 616 128 611 128 520V128C128 41 120 34 44 28V0H304V28C221 34 212 41 212 128V318C229 321 242 318 266 291C355 185 436 87 514 0H667Z"></path></g><g transform="matrix(.0091,0,0,-0.0091,8.749,3.132)"><path d="M138 535C169 535 191 560 191 589C191 620 168 644 139 644S85 620 85 589C85 560 110 535 138 535ZM257 0V30C192 35 185 43 185 109V453C142 435 94 422 40 414V386C101 378 104 372 104 311V109C104 41 97 35 33 30V0H257Z"></path></g></svg>= 4.26 <i>μ</i>M and intersection is (-4.26, 0.03).</div>

Journal of Oncology

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Figure 4

Figure 4: Interaction of Anticancer Drugs with Human Organic Anion Transporter hOAT4 