Chueaphromsri Phongsakorn, Kunhorm Phongsakorn, Chaicharoenaudomrung Nipha, Noisa Parinya
Laboratory of Cell-Based Assays and Innovations, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand.
Biotechnol Lett. 2025 Feb 26;47(2):29. doi: 10.1007/s10529-025-03561-z.
Phellinus linteus (PL) is a medicinal fungus known for producing hispolon, a bioactive compound with antioxidant, anti-inflammatory, and anticancer properties. However, the natural scarcity of PL and the unsuccessful cultivation of its fruiting bodies have led to the exploration of alternative methods for enhancing its bioactive compound production. In this study, static fermentation was employed, and Valproic acid (VPA), a histone deacetylase inhibitor (HDACi), was added to the culture medium to induce epigenetic modifications and enhance hispolon production. After 30 days of fermentation, the hispolon concentration was analyzed using high-performance liquid chromatography (HPLC), mycelial dry weight was measured, and the expression of hispolon synthesis-related enzymes was quantified using quantitative PCR (qPCR). Additionally, the anticancer potential of the fermented media was assessed in human breast adenocarcinoma HTB-26 cells using assays for cytotoxicity, reactive oxygen species (ROS) formation, apoptosis, antioxidant activity, and autophagy markers. The results revealed that the addition of 400 µM VPA increased hispolon production by 120% and mycelial dry weight by 41%, likely due to enhanced transcriptional accessibility. Furthermore, the PL fermentation media significantly inhibited HTB-26 cell growth through the induction of ROS formation, autophagy, and apoptosis. These findings suggest that VPA-enhanced static fermentation of PL offers a promising strategy for optimizing hispolon production and developing effective anticancer therapeutics.
桑黄（PL）是一种药用真菌，以产生漆斑菌醇而闻名，漆斑菌醇是一种具有抗氧化、抗炎和抗癌特性的生物活性化合物。然而，桑黄的天然稀缺性及其子实体栽培的不成功导致人们探索提高其生物活性化合物产量的替代方法。在本研究中，采用静态发酵，并将组蛋白去乙酰化酶抑制剂（HDACi）丙戊酸（VPA）添加到培养基中，以诱导表观遗传修饰并提高漆斑菌醇的产量。发酵30天后，使用高效液相色谱（HPLC）分析漆斑菌醇浓度，测量菌丝体干重，并使用定量聚合酶链反应（qPCR）定量漆斑菌醇合成相关酶的表达。此外，使用细胞毒性、活性氧（ROS）形成、细胞凋亡、抗氧化活性和自噬标记物检测法，在人乳腺腺癌HTB - 26细胞中评估发酵培养基的抗癌潜力。结果显示，添加400µM VPA可使漆斑菌醇产量提高120%，菌丝体干重提高41%，这可能是由于转录可及性增强所致。此外，桑黄发酵培养基通过诱导ROS形成、自噬和细胞凋亡，显著抑制HTB - 26细胞生长。这些发现表明，VPA增强的桑黄静态发酵为优化漆斑菌醇生产和开发有效的抗癌治疗方法提供了一种有前景的策略。
