Efficacy of Caffeic Acid Phenethyl Ester (CAPE) in skin B16-F0 melanoma tumor bearing C57BL/6 mice
Efficacy of Caffeic Acid Phenethyl Ester (CAPE) in skin B16-F0 melanoma tumor bearing C57BL/6 mice
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DOI：
10.1007/s10637-009-9334-5
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发表时间：
2011-02-01
影响因子：
3.4
通讯作者：
Moridani, Majid Y.
中科院分区：
文献类型：
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作者：
Kudugunti, Shashi K.;Vad, Nikhil M.;Moridani, Majid Y.
在目前的工作中，我们研究了咖啡酸苯乙酯（CAPE）作为抗黑色素瘤药物在五种黑色素瘤细胞系B16-F0、B16 F10、SK-MEL-28、SK-MEL-5和MeWo中的体外疗效，以及在C57 BL/6小鼠皮肤B16-F0黑色素瘤模型中的体内疗效研究。CAPE对上述5种黑色素瘤细胞系的IC_（50）（48 h）均为15 μ M。CAPE（20-200 μ M）导致B16-F0细胞中16- 54%的细胞内GSH消耗，以及活性氧（ROS）形成的10-25倍增加。CAPE（15-30 μ M）引起B16-F0细胞凋亡增加5-7倍。CAPE（10、20和30 mg/Kg/天）分别导致肿瘤大小生长抑制39 A +/-33%、54 A +/-36%和57 A +/-18%。与对照组66 A +/- 14 IU/L相比，相应治疗导致血浆丙氨酸氨基转移酶（ALT）水平分别为85 A +/- 18、107 A +/- 26、154 A +/- 35 IU/L。在相应剂量下，通过肝匀浆中丙二醛（MDA）形成测定的脂质过氧化水平分别为255 A +/- 8 μ M、304 A +/- 21 μ M和342 A +/- 14 μ M，而对照组为208 A +/- 6 μ M。肾匀浆中的MDA水平分别为263 A +/- 21 μ M、282 A +/- 18 μ M和350 A +/- 28 μ M，而对照组为212 A +/- 8 μ M。与对照组相比，CAPE（10、20、30 mg/Kg/天）给药使肝脏中游离巯基含量分别降低21 A +/-15%、40 A +/-17%和44 A +/- 19%，肾匀浆中游离巯基含量分别降低25 A +/-15%、37 A +/-18%和40 A +/-22%。我们的研究表明，10 mg/Kg/天的CAPE具有显著的抗黑色素瘤功效，毒性最小。
In current work, we investigated the in-vitro efficacy of Caffeic acid Phenethyl Ester (CAPE) as an anti-melanoma agent in five melanoma cell lines B16-F0, B16F10, SK-MEL-28, SK-MEL-5, and MeWo and in-vivo efficacy study in skin B16-F0 melanoma tumor model in C57BL/6 mice. The IC50 (48 h) of CAPE in above five melanoma cell lines was 15 A mu M. CAPE (20-200 A mu M) led to intracellular GSH depletion of 16-54%, and 10-25 fold increase in Reactive Oxygen Species (ROS) formation in B16-F0 cells. CAPE (15-30 A mu M) caused 5-7 fold increase in apoptosis in B16-F0 cells. CAPE (10, 20 and 30 mg/Kg/day) led to tumor size growth inhibition by 39 A +/- 33%, 54 A +/- 36%, and 57 A +/- 18%, respectively. The respective therapies led to plasma Alanine Amino Transferase (ALT) levels corresponding to 85 A +/- 18, 107 A +/- 26, 154 A +/- 35 IU/L in comparison to controls 66 A +/- 14 IU/L. At corresponding doses, the lipid peroxidation levels as measured by malondialdehyde (MDA) formation in liver homogenates were 255 A +/- 8 mu M, 304 A +/- 21 mu M, and 342 A +/- 14 mu M in comparison to 208 A +/- 6 mu M in controls. The level of MDA in kidney homogenates was 263 A +/- 21 mu M, 282 A +/- 18 mu M, and 350 A +/- 28 mu M, respectively, in comparison to 212 A +/- 8 mu M in controls. Administration of CAPE (10, 20, 30 mg/Kg/day) diminished free thiol contents in liver for 21 A +/- 15%, 40 A +/- 17%, and 44 A +/- 19% and in kidney homogenates for 25 A +/- 15%, 37 A +/- 18%, and 40 A +/- 22%, respectively, as compared to controls. Our study suggests that CAPE at 10 mg/Kg/day has significant anti-melanoma efficacy with minimal toxicity.