Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China; Nanjing Jinling Hospital, Nanjing, Jiangsu, China.
Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China; Key Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu, China.
Life Sci. 2021 Feb 15;267:118910. doi: 10.1016/j.lfs.2020.118910. Epub 2020 Dec 24.
Cancer cells exhibit a metabolic change called aerobic glycolysis compared with normal cells. Balanophorin B is a terpenoid ingredient reported from the genus Balanophora. In this research, we studied the effect of balanophorin B on glycolysis of HepG2 cells and Huh-7 cells under hypoxia.
The Warburg effect was monitored by assessing glucose uptake, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Key enzymes in the glycolytic pathway and HIF-1α protein expression and degradation were analyzed by real-time PCR and western blotting. The anti-cancer effect of balanophorin B in vivo was also investigated.
Balanophorin B inhibited the proliferation, glucose uptake, and ECAR in both HepG2 cells and Huh-7 cells. In addition, balanophorin B inhibited the protein level of HIF-1α and its downstream targets LDHA and HKII under hypoxia, whereas HIF-1α mRNA level did not change after balanophorin B treatment. The HIF-1α plasmid reversed the inhibition of balanophorin B on glycolysis, and the proteasome inhibitor MG132 attenuated the effect of balanophorin B on HIF-1α protein expression, suggesting that balanophorin B might post-transcriptionally affect HIF-1α. Moreover, balanophorin B increased the expression of VHL and PHD2. HIF-1α siRNA also greatly attenuated the inhibitory effect of balanophorin B on HepG2 cells glucose uptake. Balanophorin B significantly inhibited tumor growth in vivo, without causing obvious toxicity to mice.
These data suggest that balanophorin B inhibits glycolysis probably via an HIF-1α-dependent pathway, and the ubiquitin-proteasome pathway was greatly involved in the induction of balanophorin B on HIF-1α degradation.
与正常细胞相比，癌细胞表现出一种称为有氧糖酵解的代谢变化。Balanophorin B 是从 Balanophora 属中报道的一种萜类成分。在这项研究中，我们研究了 balanophorin B 对缺氧条件下 HepG2 细胞和 Huh-7 细胞糖酵解的影响。
通过评估葡萄糖摄取、耗氧率 (OCR) 和细胞外酸化率 (ECAR) 来监测瓦伯格效应。通过实时 PCR 和 Western blot 分析糖酵解途径中的关键酶以及 HIF-1α 蛋白表达和降解。还研究了 balanophorin B 在体内的抗癌作用。
Balanophorin B 抑制了 HepG2 细胞和 Huh-7 细胞的增殖、葡萄糖摄取和 ECAR。此外，balanophorin B 抑制了缺氧下 HIF-1α及其下游靶标 LDHA 和 HKII 的蛋白水平，而 balanophorin B 处理后 HIF-1α mRNA 水平没有变化。HIF-1α 质粒逆转了 balanophorin B 对糖酵解的抑制作用，蛋白酶体抑制剂 MG132 减弱了 balanophorin B 对 HIF-1α 蛋白表达的影响，表明 balanophorin B 可能在后转录水平上影响 HIF-1α。此外，balanophorin B 增加了 VHL 和 PHD2 的表达。HIF-1α siRNA 也大大减弱了 balanophorin B 对 HepG2 细胞葡萄糖摄取的抑制作用。Balanophorin B 显著抑制了体内肿瘤的生长，而对小鼠没有明显的毒性。
这些数据表明，balanophorin B 抑制糖酵解可能是通过 HIF-1α 依赖性途径，泛素-蛋白酶体途径在诱导 balanophorin B 降解 HIF-1α 中起重要作用。
