ERK1/2-Dependent Inhibition of Glycolysis in Curcumin-Induced Cytotoxicity of Prostate Carcinoma Cells

<div>Antiglycolytic and cytotoxic effects of curcumin and PD98059 in 3D spheroid culture. Spheroids were cultured in ultralow cluster plates and were treated with curcumin (40 <i>μ</i>M) and PD98059 (50 <i>μ</i>M), alone or in combination, in DMEM containing 3.8 <i>μ</i>M lactic acid for 48 h. (a) Vitality staining of spheroids: (i) phase-contrast image, (ii) fluorescent image of fluorescein diacetate(+) live cells in green, (iii) propidium iodide(+) dead cells in red, and (iv) merged. (b) Spheroid viability. (c) The expression levels of p-MEK, p-ERK1/2, and key enzymes in glucose metabolism, apoptosis, and necroptosis. Different letters above error bars are significantly different (<span class="nowrap"><svg height="9.2729pt" id="M20" style="vertical-align:-0.6370001pt" version="1.1" viewbox="-0.0498162 -8.6359 44.8393 9.2729" width="44.8393pt" 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="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"></path></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"></path></g><g transform="matrix(.013,0,0,-0.013,22.921,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><path d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"></path></g></svg>).</span> CCM: curcumin; PD: PD98059; HK: hexokinae; PFKP: phosphofructokinase platelet; PDH: pyruvate dehydrogenase.</div>

BioMed Research International

fig6

Figure 6

Figure 6: ERK1/2-Dependent Inhibition of Glycolysis in Curcumin-Induced Cytotoxicity of Prostate Carcinoma Cells 