Phenoxodiol is an isoflavone derivative with antitumor activity[1]. Phenoxodiol can induce G1 arrest in cells through p53-independent induction of p21WAF1/CIP1, resulting in loss of cyclin-dependent kinase 2 activity[2]. Phenoxodiol can induce apoptosis and target plasma membrane electron transport (PMET)[3].
In vitro, treatment of prostate cancer cell lines (LNCaP, DU145 and PC3 cells) with Phenoxodiol (10, 30μM) for 24h and 48h upregulated the expression of p21WAF1 in all cell lines and induced cell cycle arrest at the G1/S phase[4]. Pretreatment of epithelial ovarian cancer (EOC) cells with Phenoxodiol (10μg/mL) for 2h significantly reduced cell viability and enhanced the sensitivity of cells to chemotherapy[5]. Phenoxodiol (0-10μg/mL) treatment of LNCaP cells for 24h significantly inhibited cell proliferation and reduced colony formation in a dose-dependent manner[6].
In vivo, Phenoxodiol (10mg/kg) was orally treated for 16 days in mice with U2OS cell xenografts. When combined with Doxorubicin (1mg/kg, i.p.), it was able to significantly inhibit tumor growth. The tumor growth inhibition effect of the group receiving only single treatment was weak[7].
References:
[1] Choueiri T K, Wesolowski R, Mekhail T M. Phenoxodiol: isoflavone analog with antineoplastic activity[J]. Current oncology reports, 2006, 8: 104-107.
[2] Aguero M F, Facchinetti M M, Sheleg Z, et al. Phenoxodiol, a novel isoflavone, induces G1 arrest by specific loss in cyclin-dependent kinase 2 activity by p53-independent induction of p21WAF1/CIP1[J]. Cancer research, 2005, 65(8): 3364-3373.
[3] Herst P M, Petersen T, Jerram P, et al. The antiproliferative effects of phenoxodiol are associated with inhibition of plasma membrane electron transport in tumour cell lines and primary immune cells[J]. Biochemical pharmacology, 2007, 74(11): 1587-1595.
[4] Mahoney S, Arfuso F, Millward M, et al. The effects of phenoxodiol on the cell cycle of prostate cancer cell lines[J]. Cancer cell international, 2014, 14: 1-12.
[5] Alvero A B, O'Malley D, Brown D, et al. Molecular mechanism of phenoxodiol‐induced apoptosis in ovarian carcinoma cells[J]. Cancer: Interdisciplinary International Journal of the American Cancer Society, 2006, 106(3): 599-608.
[6] Yao C, Wu S, Li D, et al. Co-administration phenoxodiol with doxorubicin synergistically inhibit the activity of sphingosine kinase-1 (SphK1), a potential oncogene of osteosarcoma, to suppress osteosarcoma cell growth both in vivo and in vitro[J]. Molecular oncology, 2012, 6(4): 392-404.
[7] Aguero M F, Venero M, Brown D M, et al. Phenoxodiol inhibits growth of metastatic prostate cancer cells[J]. The Prostate, 2010, 70(11): 1211-1221.
Phenoxodiol是一种异黄酮衍生物，具有抗肿瘤活性[1]。Phenoxodiol能够通过p21WAF1/CIP1的p53独立诱导，导致周期蛋白依赖性激酶2活性的损失，从而诱导细胞G1阻滞[2]。Phenoxodiol能够引起细胞凋亡，靶向质膜电子传递（PMET）[3]。
在体外，Phenoxodiol（10, 30μM）处理前列腺癌细胞系（LNCaP、DU145和PC3细胞）24h和48h，上调了所有细胞系中p21WAF1的表达，诱导了细胞周期停滞在G1/S期[4]。Phenoxodiol（10μg/mL）预处理上皮性卵巢癌（EOC）细胞2h，显著降低了细胞活力，增强了细胞对化疗的敏感性[5]。Phenoxodiol（0-10μg/mL）处理LNCaP细胞24h，以剂量依赖性方式显著抑制了细胞的增殖，减少了集落形成[6]。
在体内，Phenoxodiol（10mg/kg）通过口服治疗U2OS细胞异种移植小鼠16天，在与Doxorubicin（1mg/kg, i.p.）联合治疗的情况下能够显著抑制肿瘤生长，仅接受单一治疗的组肿瘤生长抑制效果较弱[7]。