Department of Respiratory Therapy, China Medical University, Taichung 406, Taiwan.
Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan.
Int J Mol Sci. 2022 Jan 4;23(1):538. doi: 10.3390/ijms23010538.
Bisdemethoxycurcumin (BDMC) has biological activities, including anticancer effects in vitro; however, its anticancer effects in human glioblastoma (GBM) cells have not been examined yet. This study aimed to evaluate the tumor inhibitory effect and molecular mechanism of BDMC on human GBM 8401/ cells in vitro and in vivo. In vitro studies have shown that BDMC significantly reduced cell viability and induced cell apoptosis in GBM 8401/ cells. Furthermore, BDMC induced apoptosis via inhibited Bcl-2 (anti-apoptotic protein) and increased Bax (pro-apoptotic proteins) and cytochrome c release in GBM 8401/ cells in vitro. Then, twelve BALB/c-nude mice were xenografted with human glioblastoma GBM 8401/ cancer cells subcutaneously, and the xenograft nude mice were treated without and with BDMC (30 and 60 mg/kg of BDMC treatment) every 3 days. GBM 8401/ cell xenografts experiment showed that the growth of the tumors was significantly suppressed by BDMC administration at both doses based on the reduction of tumor size and weights. BDMC did not change the body weight and the H&E histopathology analysis of liver samples, indicating that BDMC did not induce systemic toxicity. Meanwhile, treatment with BDMC up-regulated the expressions of BAX and cleaved caspase-3, while it down-regulated the protein expressions of Bcl-2 and XIAP in the tumor tissues compared with the control group. This study has demonstrated that BDMC presents potent anticancer activity on the human glioblastoma GBM 8401/ cell xenograft model by inducing apoptosis and inhibiting tumor cell proliferation and shows the potential for further development to the anti-GBM cancer drug.
双去甲氧基姜黄素(BDMC)具有生物活性,包括体外抗癌作用;然而,其在人类脑胶质瘤(GBM)细胞中的抗癌作用尚未得到检验。本研究旨在评估 BDMC 在体外和体内对人 GBM 8401/细胞的肿瘤抑制作用和分子机制。体外研究表明,BDMC 显著降低 GBM 8401/细胞活力并诱导细胞凋亡。此外,BDMC 通过抑制 Bcl-2(抗凋亡蛋白)和增加 Bax(促凋亡蛋白)和细胞色素 c 在 GBM 8401/细胞中的释放诱导细胞凋亡。然后,将 12 只 BALB/c-裸鼠皮下接种人脑胶质瘤 GBM 8401/癌细胞,并用 BDMC(BDMC 治疗 30 和 60mg/kg)每 3 天处理裸鼠。GBM 8401/细胞异种移植实验表明,BDMC 给药在两个剂量下均显著抑制肿瘤生长,基于肿瘤大小和重量的减少。BDMC 没有改变体重和肝组织样本的 H&E 组织病理学分析,表明 BDMC 没有引起全身毒性。同时,与对照组相比,BDMC 处理上调了肿瘤组织中 BAX 和 cleaved caspase-3 的表达,而下调了 Bcl-2 和 XIAP 的蛋白表达。本研究表明,BDMC 通过诱导细胞凋亡、抑制肿瘤细胞增殖,对人 GBM 8401/细胞异种移植模型表现出强大的抗癌活性,并具有进一步开发抗 GBM 癌症药物的潜力。