Arizona Cancer Center, University of Arizona, Tucson, AZ, United States; Department of Pharmacology, University of Arizona, Tucson, AZ, United States.
Arizona Cancer Center, University of Arizona, Tucson, AZ, United States; Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, United States.
Arch Biochem Biophys. 2014 Sep 15;558:143-52. doi: 10.1016/j.abb.2014.06.021. Epub 2014 Jul 5.
One of the primary components of the East Indian sandalwood oil (EISO) is α-santalol, a molecule that has been investigated for its potential use as a chemopreventive agent in skin cancer. Although there is some evidence that α-santalol could be an effective chemopreventive agent, to date, purified EISO has not been extensively investigated even though it is widely used in cultures around the world for its health benefits as well as for its fragrance and as a cosmetic. In the current study, we show for the first time that EISO-treatment of HaCaT keratinocytes results in a blockade of cell cycle progression as well as a concentration-dependent inhibition of UV-induced AP-1 activity, two major cellular effects known to drive skin carcinogenesis. Unlike many chemopreventive agents, these effects were not mediated through an inhibition of signaling upstream of AP-1, as EISO treatment did not inhibit UV-induced Akt or MAPK activity. Low concentrations of EISO were found to induce HaCaT cell death, although not through apoptosis as annexin V and PARP cleavage were not found to increase with EISO treatment. However, plasma membrane integrity was severely compromised in EISO-treated cells, which may have led to cleavage of LC3 and the induction of autophagy. These effects were more pronounced in cells stimulated to proliferate with bovine pituitary extract and EGF prior to receiving EISO. Together, these effects suggest that EISO may exert beneficial effects upon skin, reducing the likelihood of promotion of pre-cancerous cells to actinic keratosis (AK) and skin cancer.
东印度檀香油（EISO）的主要成分之一是α-檀香醇，这种分子已被研究用于预防皮肤癌的化学预防剂。尽管有一些证据表明α-檀香醇可能是一种有效的化学预防剂，但迄今为止，尽管它在世界各地因其对健康的益处以及其香味和作为化妆品而被广泛使用，但尚未广泛研究提纯的 EISO。在目前的研究中，我们首次表明，EISO 处理 HaCaT 角质形成细胞会导致细胞周期进程受阻，以及 UV 诱导的 AP-1 活性的浓度依赖性抑制，这是已知导致皮肤致癌的两种主要细胞效应。与许多化学预防剂不同，这些作用不是通过抑制 AP-1 上游的信号转导介导的，因为 EISO 处理不会抑制 UV 诱导的 Akt 或 MAPK 活性。发现低浓度的 EISO 诱导 HaCaT 细胞死亡，尽管不是通过细胞凋亡，因为 Annexin V 和 PARP 切割未发现随着 EISO 处理而增加。然而，EISO 处理的细胞的质膜完整性严重受损，这可能导致 LC3 的切割和自噬的诱导。在用牛垂体提取物和 EGF 刺激细胞增殖之前，用 EISO 处理这些细胞，这些作用更为明显。这些作用表明 EISO 可能对皮肤有益，降低将癌前细胞促进为光化性角化病（AK）和皮肤癌的可能性。
