Radiation and Cancer Therapeutics Lab, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Nutr Cancer. 2022;74(1):237-249. doi: 10.1080/01635581.2020.1870705. Epub 2021 Jan 15.
Polydatin, a natural analogue of resveratrol, has many biological activities. The better bioavailability of polydatin than resveratrol makes it an ideal candidate for therapy. Polydatin has protective effects against various diseases (cardiovascular, neurological, inflammatory, etc.) including cancer. However, its mechanism of action has not been fully established. Therefore, the present study was initiated to explore the mechanism/s associated with chemotherapeutic effects of polydatin in using lung cancer A549 cells. The effects of polydatin on cell proliferation and metastasis were assessed using various parameters like MTT, colony formation, DNA damage, apoptosis, and wound healing. Polydatin treatment reduced the proliferation of A549 cells by inducing DNA damage and cell cycle arrest in a concentration-dependent manner. The inhibition of cell proliferation was induced by dual mechanism of senescence and apoptosis. Proteins involved in various pathways were studied using western blotting and immunocytochemistry. Interestingly, senescent and apoptotic cells induced a differential bystander response (proliferative/toxic) in naïve A549 cells. Our results show that polydatin can induce both senescence and apoptosis in A549 cells in a concentration-dependent manner and the differential bystander effects induced by polydatin are regulated by mTOR pathway.
白藜芦醇的天然类似物虎杖苷具有许多生物活性。与白藜芦醇相比，虎杖苷具有更好的生物利用度，使其成为治疗的理想候选药物。虎杖苷对各种疾病（心血管、神经、炎症等）包括癌症都具有保护作用。然而，其作用机制尚未完全确定。因此，本研究旨在使用肺癌 A549 细胞探索虎杖苷在化疗作用中的相关机制。通过 MTT、集落形成、DNA 损伤、凋亡和伤口愈合等各种参数评估虎杖苷对细胞增殖和转移的影响。虎杖苷处理以浓度依赖的方式通过诱导 DNA 损伤和细胞周期阻滞来降低 A549 细胞的增殖。细胞增殖的抑制是通过衰老和凋亡的双重机制诱导的。使用 Western blot 和免疫细胞化学研究了参与各种途径的蛋白质。有趣的是，衰老和凋亡细胞在未成熟的 A549 细胞中诱导了不同的旁观者反应（增殖/毒性）。我们的结果表明，虎杖苷可以浓度依赖性方式诱导 A549 细胞中的衰老和凋亡，并且虎杖苷诱导的差异旁观者效应受 mTOR 途径调节。
