Colossolactone-G synergizes the anticancer properties of 5-fluorouracil and gemcitabine against colorectal cancer cells.
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.
['Algehani|Rinad A|RA|', 'Abou Khouzam|Raefa|R|', 'Hegazy|Gehan A|GA|', 'Alamoudi|Aliaa A|AA|', 'El-Halawany|Ali M|AM|', 'El Dine|Riham S|RS|', 'Ajabnoor|Ghada A|GA|', 'Al-Abbasi|Fahad A|FA|', 'Baghdadi|Mohammed A|MA|', 'Elsayed|Ibrahim|I|', 'Hattori|Masao|M|', 'Al-Abd|Ahmed M|AM|']
D000970:Antineoplastic Agents D000971:Antineoplastic Combined Chemotherapy Protocols D017209:Apoptosis D001343:Autophagy D002453:Cell Cycle D045744:Cell Line, Tumor D015179:Colorectal Neoplasms D003841:Deoxycytidine D004357:Drug Synergism D005472:Fluorouracil D006801:Humans D007783:Lactones D014315:Triterpenes
Colossolactone-G 5-fluorouracil Gemcitabine Colorectal cancer Apoptosis Autophagy