P19 一种帕森宁类似物在急性淋巴细胞白血病细胞中诱导细胞谱系依赖性凋亡和免疫调节信号传导。
P19 a Parthenin Analog Induces Cell Lineage Dependent Apoptotic and Immunomodulatory Signaling in Acute Lymphoid Leukemia Cells.
发表日期:2023
作者:
Vishal Sharma, Samriti Dhawan, Ajay Kumar, Jagdeep Kaur
来源:
PHARMACOLOGY & THERAPEUTICS
摘要:
白血病是一种影响血液和骨髓的癌症。急性淋巴细胞白血病,也称为 ALL,被认为是最致命的癌症之一。由于各种癌症病例的迅速增加和癌细胞耐药性的发展,有必要鉴定具有更有效抗癌特性的新型先导分子。人们对使用草药产品/类似物作为多组分制剂(作为抗癌剂和免疫调节剂)来治疗癌症越来越感兴趣。在本研究中,我们尝试探索 P19(一种小白菊类似物)在 ALL 中的抗癌和免疫调节活性。据报道,P19 通过显着产生 NO 来触发人白血病 HL-60 细胞中的细胞凋亡信号事件,从而表现出抗癌功效。与这一发现相反,Raji 细胞中 P19 介导的细胞凋亡不需要 ROS 和 NO。据观察,P19 的作用机制依赖于癌细胞谱系。 P19 对 ALL 表现出非常有效的抗癌特性(IC50 3μM)。分子研究表明,P19 通过 Bax 定位到线粒体并增强细胞质中的胞质钙来诱导线粒体介导的细胞凋亡。 caspase 3、caspase 8 和 PARP 裂解的进一步激活表明 caspase 介导的细胞凋亡参与其中。抗增殖活性揭示了 P19 处理后端粒酶抑制和细胞周期停滞在 G0/G1 期。 P19 的免疫调节作用揭示了 Jurkat 和 THP 细胞中 INFɣ 和 NO 的产生增强。由于其对白血病细胞的抗增殖和免疫调节潜力,P19 可以进一步探索作为针对白血病的有效疗法。
Leukemia is a type of cancer that affects the blood and bone marrow. Acute lymphoid leukaemia, also known as ALL, is regarded as one of the deadliest forms of cancer. Due to the rapid increase in various cancer cases and the development of resistance in cancer cells, it is necessary to identify novel lead molecules with more potent anticancer properties. There is a growing interest in using herbal products/analogs as multi-component agents (as anticancer agents and immunomodulators) for cancer treatment. In the present investigation, an attempt has been made to explore the anticancer and immunomodulatory activity of P19, an analog of parthenin in ALL. P19 was reported to exhibit anticancer efficacy by triggering apoptotic signaling events in human leukaemia HL-60 cells by significant NO production. In contrast to this finding, ROS and NO were not required for P19-mediated apoptosis in Raji cells. The mechanism of action of P19 was observed to be cancer cell lineage dependent. P19 demonstrated very effective anticancer properties against ALL (IC50 3µM). Molecular investigations revealed that P19 induced mitochondrion mediated apoptosis by Bax localization to mitochondria and enhanced cytosolic calcium in the cytoplasm. Further activation of the caspase 3, caspase 8 and PARP cleavage suggested the involvement of the caspase-mediated apoptosis. Anti-proliferative activity revealed the telomerase inhibition and cell cycle arrest in G0/G1 phase after P19 treatment. Immunomodulatory effects of the P19 revealed the enhanced INFɣ and NO production in Jurkat and THP cells. Owing to its antiproliferative and immunomodulatory potential against leukemia cells P19 can further be explored as effective therapeutics against leukemia.