自噬
细胞凋亡
ATG5型
吉西他滨
细胞周期
化学
癌症研究
细胞周期检查点
结直肠癌
程序性细胞死亡
癌细胞
细胞生长
癌症
生物
医学
内科学
生物化学
作者
Rinad Algehani,Raefa Abou Khouzam,Gehan A. Hegazy,Aliaa A. Alamoudi,Ali M. El-Halawany,Riham Salah El Dine,Ghada A. Ajabnoor,Fahad A. Al-Abbasi,Mohammed Baghdadi,Ibrahim Elsayed,Masao Hattori,Ahmed M. Al‐Abd
标识
DOI:10.1016/j.biopha.2021.111730
摘要
Several terpenoids were isolated from Ganoderma colossum with potential chemotherapeutic properties against different solid tumor cells. Herein, we further assessed the potential chemomodulatory effects of colossolactone-G to gemcitabine (GCB) and 5-fluorouracil (5-FU) against colorectal cancer cells. Colossolactone-G induced moderate cell killing effects against both HT-29 and HCT-116 cells, with IC50’s of 90.5 ± 1.7 µM and 22.3 ± 3.9 µM, respectively. Equitoxic combination demonstrated a synergistic effect between colossolactone-G and GCB, or 5-FU with combination indices ranging from 0.22 to 0.67. Both GCB and 5-FU induced moderate cell cycle arrest at G0/G1-phase and S-phase. Despite colossolactone-G’s lack of influence on cell cycle distribution, it significantly potentiated GCB- and 5-FU-induced cell cycle arrest. Similarly, colossolactone-G treatment alone did not induce pronounced apoptosis in both cell lines. However, 5-FU and GCB induced significant apoptosis which was further potentiated via combination with colossolactone-G. Furthermore, colossolactone-G significantly increased autophagic cell death response in both HCT-116 and HT-29 cells and potentiated 5-FU- and GCB-induced autophagic cell death. The influence of colossolactone-G alone or in combination with GCB or 5-FU on the apoptosis and autophagy were confirmed by qPCR analysis for the expression of several key apoptosis and autophagy genes such as, TRAIL, TP53INP1, BNIP3, hp62, ATG5, ATG7, Lamp2A and the golden standard for autophagy (LC3-II). In conclusion, a synergistic effect in terms of anticancer properties was observed when colossolactone-G was combined with 5-FU and GCB, where it influenced both apoptosis and autophagic cell death mechanisms.
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