TartroonD(TRL)是由Teredinibacterturnerae产生的,一种共生的降解纤维素的细菌。免疫原性细胞死亡(ICD)诱导有助于更好和更持久的抗癌治疗反应。接受ICD的肿瘤细胞会触发免疫系统的激活,作为疫苗。
目的:本研究旨在评估TRL诱导ICD。
方法:通过SRB测定评价细胞活力。细胞应激,细胞死亡,通过流式细胞术和免疫印迹评估ICD特征和抗原呈递分子。
结果:TRL对7种肿瘤细胞系(L929,HCT116,B16-F10,WM293A,SK-MEL-28,PC-3M,和MCF-7)和非肿瘤细胞(HEK293A),抑制浓度平均值(IC50)为0.03uM至13uM。转移性黑色素瘤,SK-MEL-28,B16-F10,和WM293A,是更敏感的细胞系,IC50范围为0.07至1.2uM。TRL诱导细胞凋亡以及自噬和内质网应激,并释放ICD的典型损伤相关分子模式(DAMPs),如钙网蛋白,ERp57和HSP70暴露,和HMGB1释放。此外,暴露于TRL的黑色素瘤B16-F10增加了抗原呈递分子MHCII和CD1d的表达,并诱导了C57BL/6小鼠脾细胞的激活。
结论:尽管靶向治疗和免疫疗法取得了最新进展,超过一半的患者无法治愈晚期转移性黑色素瘤.ICD诱导剂对抗癌治疗产生更好和持久的反应。我们的发现揭示了一种在黑色素瘤中诱导ICD的海洋抗癌候选物。
Tartrolon D (TRL) is produced by Teredinibacter turnerae, a symbiotic cellulose-degrading bacteria in shipworm gills. Immunogenic cell death (ICD) induction contributes to a better and longer-lasting response to anticancer treatment. Tumor cells undergoing ICD trigger activation of the immune system, as a vaccine.
OBJECTIVE: This study aimed to evaluate ICD induction by TRL.
METHODS: Cell viability was evaluated by SRB assay. Cell stress, cell death, ICD features and antigen-presenting molecules were evaluated by flow cytometry and immunoblot.
RESULTS: TRL showed antiproliferative activity on 7 tumor cell lines (L929, HCT 116, B16-F10, WM293A, SK-MEL-28, PC-3M, and MCF-7) and a non-tumor cell (HEK293A), with an inhibition concentration mean (IC50) ranging from 0.03 μM to 13 μM. Metastatic melanomas, SK-MEL-28, B16-F10, and WM293A, were more sensitive cell lines, with IC50 ranging from 0.07 to 1.2 μM. TRL induced apoptosis along with autophagy and endoplasmic reticulum stress and release of typical damage-associated molecular patterns (DAMPs) of ICD such
calreticulin, ERp57, and HSP70 exposure, and HMGB1 release. Additionally, melanoma B16-F10 exposed to TRL increased expression of antigen-presenting molecules MHC II and CD1d and induced activation of splenocytes of C57BL/6 mice.
CONCLUSIONS: In spite of recent advances provided by target therapy and immunotherapy, advanced metastatic melanoma is incurable for more than half of patients. ICD inducers yield better and long-lasting responses to anticancer treatment. Our findings shed light on an anticancer candidate of marine origin that induces ICD in melanoma.