B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Ahmedabad, Gujarat, India.
Department of Life Science, Gujarat University, Ahmedabad, Gujarat, India.
Mol Divers. 2022 Dec;26(6):3225-3240. doi: 10.1007/s11030-022-10384-x. Epub 2022 Feb 7.
Sirtuins (SIRTs) overexpression serves as a potential therapeutic target for TNBC because it is associated with bioactivities of cancer stem cells (CSCs), resistance to chemotherapy, and metastasis. Irrespective of the availability of synthetic SIRT inhibitors, new SIRT inhibitors with enhanced potency and lesser side effects serve as current unmet needs. Therefore, bioactive dietary compounds; kaempferol (KMP) and apigenin (API) were investigated for their anti-SIRTs potential. We observed KMP and API inhibits cellular proliferation by DNA damage and S-phase cell cycle arrest in TNBC Cells. They also suppress stemness properties in TNBCs as observed in experiments of mammosphere formation and clonogenic potential. Our mechanistic approach indicated that KMP and API inhibited SIRT3 and SIRT6 proteins, as evidenced by our in silico and in vitro experiment. Collectively, our studies suggest that KMP and API are promising candidates to be further developed as sirtuin modulators against TNBCs.
Sirtuins（SIRTs）过表达可作为三阴性乳腺癌（TNBC）的潜在治疗靶点，因为它与癌症干细胞（CSCs）的生物活性、化疗耐药性和转移有关。尽管有合成的 SIRT 抑制剂，但具有更强效力和更少副作用的新型 SIRT 抑制剂仍是当前未满足的需求。因此，我们研究了生物活性膳食化合物——山柰酚（KMP）和芹菜素（API），以评估它们的抗 SIRTs 潜力。我们观察到 KMP 和 API 通过 DNA 损伤抑制 TNBC 细胞的细胞增殖，并通过 S 期细胞周期阻滞抑制 TNBC 中的干性特征，如在乳腺球体形成和克隆形成潜力实验中观察到的那样。我们的机制研究表明，KMP 和 API 抑制 SIRT3 和 SIRT6 蛋白，这一点得到了我们的计算机模拟和体外实验的证实。总的来说，我们的研究表明，KMP 和 API 是有前途的候选物，可以进一步开发为针对 TNBC 的 Sirtuin 调节剂。
