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Alantolactone induces apoptosis in THP‐1 cells through STAT3, survivin inhibition, and intrinsic apoptosis pathway
Author(s) -
Ahmad Bashir,
Gamallat Yaser,
Su Pengyu,
Husain Akbar,
Rehman Ata Ur,
Zaky Mohamed Y.,
Bakheet Ahmed Musa Hago,
Tahir Naeem,
Xin Yi,
Liang Wang
Publication year - 2021
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13778
Subject(s) - survivin , apoptosis , cytochrome c , programmed cell death , thp1 cell line , microbiology and biotechnology , bcl xl , cancer cell , chemistry , intrinsic apoptosis , biology , western blot , cancer research , caspase , cell culture , biochemistry , cancer , gene , genetics
Cancer is the second foremost cause of mortality in the world, and THP‐1 cells play an important role in cancer progression. Alantolactone (ALT), a sesquiterpene lactone compound derived from Inula helenium , has a number of biological activities including antibacterial, antifungal, and anticancer. The current study was conducted to investigate the effects of ALT on THP‐1 cells and its underlying molecular mechanisms. THP‐1 cells were cultured and treated with ALT (20, 40 µM) for 12 hr, and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, cell morphology, live/dead, and apoptosis assays were performed. The gene expressions at the protein level were checked through Western blot. Results show that ALT decreased cell viability and increased cell death and apoptosis. We found that ALT inhibited STAT3 and survivin expression. Furthermore, ALT induced mitochondrial‐dependent apoptosis through a decrease in B‐cell lymphoma‐2 (Bcl‐2) and Bcl‐xL and increase in Bax expression, resulting in the release of cytochrome c (Cyt‐c) from mitochondria. Cyt‐c release from mitochondria further increased cleaved (cl) caspase‐3 and cl‐PARP expression and led the cells to apoptosis. Therefore, ALT might be a good therapy for the progression due to THP‐1 cells.