Jin Zhou, Yun Lin, Cheng Peng
State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China; Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610072, China.
Int J Biol Macromol. 2025 Feb;291:139072. doi: 10.1016/j.ijbiomac.2024.139072. Epub 2024 Dec 20.
Salvia miltiorrhiza, the anticancer properties of these components are multifaceted, encompassing the inhibition of tumor growth, prevention of the metastatic spread of cancer cells, enhancement of the sensitivity of cancer cells to chemotherapy and radiation therapy, and the suppression of angiogenesis, which is crucial for tumor growth and survival. In the context of our recent study, we have discovered that tanshinone I, one of the active components of Salvia miltiorrhiza, possesses the ability to inhibit the proliferation of ovarian cancer cells, both in laboratory settings and within living organisms. To further understand the molecular mechanisms behind this effect, we conducted a comprehensive transcriptomic analysis. Our findings indicated that tanshinone I exerts its inhibitory action by downregulating the expression of genes associated with glycolysis. Specifically, tanshinone I decreased the expression of glycolysis-related genes such as HK2 (hexokinase 2), PFK (phosphofructokinase), ENO2 (enolase 2), and LDHA (lactate dehydrogenase A). Inhibiting lactate production by tanshinone I application reduced the level of histone H3 lysine 18 lactylation (H3K18la), which reduced the expression of tumor-associated genes, such as TTK, PDGFRβ, YTHDF2 and RUBCNL. In addition, tanshinone I alleviated the immunosuppressive tumor microenvironment. In summary, tanshinone I blocks glycolysis to regulate histone H3 lysine 18 lactylation (H3K18la), which inhibits ovarian cancer cell growth, revealing the anticancer mechanism of tanshinone I.
丹参，这些成分的抗癌特性是多方面的，包括抑制肿瘤生长、预防癌细胞的转移扩散、增强癌细胞对化疗和放疗的敏感性以及抑制血管生成，而血管生成对肿瘤生长和存活至关重要。在我们最近的研究中，我们发现丹参的活性成分之一丹参酮I在实验室环境和生物体内均具有抑制卵巢癌细胞增殖的能力。为了进一步了解这种作用背后的分子机制，我们进行了全面的转录组分析。我们的研究结果表明，丹参酮I通过下调与糖酵解相关的基因表达发挥其抑制作用。具体而言，丹参酮I降低了糖酵解相关基因的表达，如HK2（己糖激酶2）、PFK（磷酸果糖激酶）、ENO2（烯醇化酶2）和LDHA（乳酸脱氢酶A）。通过应用丹参酮I抑制乳酸生成降低了组蛋白H3赖氨酸18乳酸化（H3K18la）水平，这降低了肿瘤相关基因的表达，如TTK、PDGFRβ、YTHDF2和RUBCNL。此外，丹参酮I缓解了免疫抑制性肿瘤微环境。总之，丹参酮I通过阻断糖酵解来调节组蛋白H3赖氨酸18乳酸化（H3K18la），从而抑制卵巢癌细胞生长，揭示了丹参酮I的抗癌机制。
