Vitexicarpin (Casticin), a non-isotopic tetramethoxyflavone with three phenyl rings, is a phosphatidylinositol 3-kinase (PI3K) inhibitor with high cytotoxicity [1]. Vitexicarpin can down-regulate the mRNA and protein levels of DNA methyltransferase 1(DNMT1) and induce DNA damage by binding to topoisomerase IIα[2]. Vitexicarpin has been widely used as an anticancer agent to inhibit the malignant progression of cancer cells in diverse tumor cell models[3].
In vitro, Vitexicarpin significantly inhibited the proliferation of K562, HL-60, and Kasumi-1 cells with IC50 values of 5.95μM, 4.82μM, and 15.56μM, respectively[4]. Treatment with Vitexicarpin at 8µM for 24h significantly induced apoptosis and G2/M phase arrest in S18 cells[5]. Treatment of MGC803 cells with 30µM Vitexicarpin for 72h significantly reduced cell viability, increased protein expression and mRNA levels of RECK, and decreased global DNA methylation levels[6].
In vivo, Vitexicarpin treatment (20mg/kg/day) via intragastric administration for 2 weeks significantly reduced liver injury and liver fibrosis induced by bile duct ligation in mice[7]. Vitexicarpin(0.4mg/kg) was injected intraperitoneally once every two days for 18 days, which significantly reduced the tumor volume and weight of SCC-4 cell xenograft mice without affecting the body weight of the mice[8].
References:
[1] Ramchandani S, Naz I, Lee J H, et al. An overview of the potential antineoplastic effects of casticin[J]. Molecules, 2020, 25(6): 1287.
[2] Carbone K, Gervasi F, Kozhamzharova L, et al. Casticin as potential anticancer agent: recent advancements in multi-mechanistic approaches[J]. Frontiers in Molecular Biosciences, 2023, 10: 1157558.
[3] Ding X J, Cai X M, Wang Q Q, et al. Vitexicarpin suppresses malignant progression of colorectal cancer through affecting c-Myc ubiquitination by targeting IMPDH2[J]. Phytomedicine, 2024, 132: 155833.
[4] Shen J K, Du H, Yang M, et al. Casticin induces leukemic cell death through apoptosis and mitotic catastrophe[J]. Annals of hematology, 2009, 88(8): 743-752.
[5] Liu J, Yang J, Hou Y, et al. Casticin inhibits nasopharyngeal carcinoma growth by targeting phosphoinositide 3-kinase[J]. Cancer cell international, 2019, 19(1): 348.
[6] Yang F, He K, Huang L, et al. Casticin inhibits the activity of transcription factor Sp1 and the methylation of RECK in MGC803 gastric cancer cells[J]. Experimental and Therapeutic Medicine, 2017, 13(2): 745-750.
[7] Zhou L, Dong X, Wang L, et al. Casticin attenuates liver fibrosis and hepatic stellate cell activation by blocking TGF-β/Smad signaling pathway[J]. Oncotarget, 2017, 8(34): 56267.
[8] Shang H S, Chen K W, Chou J S, et al. Casticin inhibits in vivo growth of xenograft tumors of human oral cancer SCC-4 cells[J]. in vivo, 2020, 34(5): 2461-2467.
Vitexicarpin (Casticin)是一种含有三个苯环的非同位素四甲氧基黄酮，是一种具有高细胞毒性的磷脂酰肌醇3-激酶(PI3K)抑制剂[1]。Vitexicarpin能够下调DNA甲基转移酶1的mRNA和蛋白水平，并通过与拓扑异构酶IIα结合诱导DNA损伤[2]。Vitexicarpin已被广泛用作抗癌剂，在多种肿瘤细胞模型中抑制癌细胞的恶性进展[3]。
在体外，Vitexicarpin显著抑制K562、HL-60和Kasumi-1细胞的增殖，IC50值分别为5.95μM、4.82μM和15.56μM[4]。用8µM的Vitexicarpin处理S18细胞24小时，能显著诱导细胞凋亡和G2/M期阻滞[5]。用30µM的Vitexicarpin处理MGC803细胞72小时，显著降低了细胞活力，增加了RECK的蛋白表达和mRNA水平，并降低了整体DNA甲基化水平[6]。
在体内，通过灌胃给予Vitexicarpin（20mg/kg/day）治疗2周，显著减轻了小鼠胆管结扎诱导的肝损伤和肝纤维化[7]。每两天腹腔注射一次Vitexicarpin（0.4mg/kg），持续18天，显著降低了SCC-4细胞异种移植小鼠的肿瘤体积和重量，且不影响小鼠体重 [8]。