Neoplastic cells display altered biosynthetic and bioenergetic machinery to support cell survival. Therefore, cancer cells optimally utilize all available fuel resources to pump their highly upregulated metabolic pathways. While glucose is the main carbon source, transformed cells also utilize other molecules, which can be utilized in metabolic pathways, designated as alternative fuels. Acetate is one of such alternative metabolic fuels, which is mainly consumed in carbohydrate and lipid metabolism. However, studies demonstrate the contradictory effects of acetate on tumor cell survival. Moreover, the mechanisms of its antitumor actions remain poorly understood. Further, the spectrum of acetate susceptible tumor targets needs to be characterized in order to optimize the use of acetate in maneuvering tumor progression as a therapeutic strategy. As the effect of acetate on survival properties of the tumor cells of thymic origin is not worked out, in the present study the effect of acetate was investigated against tumor cells derived from a murine thymoma designated as Dalton's Lymphoma (DL). Acetate treatment of tumor cells inhibited tumor cell survival accompanied by induction of apoptotic cell death, associated with modulated expression of cell survival regulatory HIF1α, ROS, p53, Caspase 3, Bax and HSP70 along with the elevated level of cytosolic cytochrome c. Acetate treatment also modulated the expression of pH regulators MCT-1 and V-ATPase accompanied by altered pH homeostasis. Expression of MDR and lipid metabolism regulatory molecules was also inhibited in tumor cells upon acetate exposure. Further, pre-exposure of tumor cells to α-CHC (α-cyano-4-hydroxycinnamate), an inhibitor of MCT-1, partially abrogated the cytotoxic action of acetate. These findings shed a new light regarding the effect and mechanisms of the exogenous acetate on the biology of tumor cells of thymic origin.

肿瘤细胞显示出改变的生物合成和生物能机制，以支持细胞存活。因此，癌细胞最佳地利用了所有可用的燃料资源来泵送其高度上调的代谢途径。尽管葡萄糖是主要的碳源，但转化后的细胞还利用了其他分子，这些分子可用于新陈代谢途径，被称为替代燃料。乙酸盐是此类替代性代谢燃料之一，其主要在碳水化合物和脂质代谢中消耗。然而，研究表明乙酸盐对肿瘤细胞存活的矛盾作用。此外，其抗肿瘤作用的机制仍知之甚少。此外，需要表征乙酸盐敏感性肿瘤靶标的光谱，以优化乙酸盐在操纵肿瘤进展中作为治疗策略的用途。由于乙酸盐对胸腺来源的肿瘤细胞的存活特性的影响尚未得到解决，因此在本研究中，研究了乙酸盐对源自鼠胸腺瘤的道尔顿淋巴瘤（DL）的肿瘤细胞的作用。醋酸盐处理肿瘤细胞会抑制肿瘤细胞的存活，并诱导凋亡的细胞死亡，这与细胞存活调节HIF1α，ROS，p53，Caspase 3，Bax和HSP70的表达调节以及胞浆细胞色素c水平升高有关。醋酸盐处理还调节了pH调节剂MCT-1和V-ATPase的表达，并伴随着pH稳态的改变。暴露于乙酸盐后，肿瘤细胞中的MDR和脂质代谢调节分子的表达也受到抑制。此外，将肿瘤细胞预先暴露于α-CHC（α-氰基-4-羟基肉桂酸酯），MCT-1的抑制剂可部分消除乙酸盐的细胞毒作用。这些发现为外源乙酸盐对胸腺来源肿瘤细胞生物学的作用和机制提供了新的思路。