Tumour-suppressive effects of curcumin analogs CCA-1.1 and Pentagamavunone-1 in colon cancer: In vivo and in vitro studies

Autor: Febri Wulandari, Muthi Ikawati, Sitarina Widyarini, Mitsunori Kirihata, Dhania Novitasari, Jun-ya Kato, Edy Meiyanto
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Advanced Pharmaceutical Technology & Research, Vol 14, Iss 4, Pp 317-324 (2023)
Druh dokumentu: article
ISSN: 2231-4040
0976-2094
DOI: 10.4103/JAPTR.JAPTR_315_23
Popis: This study aimed to evaluate the efficacy of Chemoprevention Curcumin Analog-1.1 (CCA-1.1) and Pentagamavunone-1 (PGV-1) in vivo and in vitro in colorectal cancer model. CCA-1.1 or PGV-1 was administered orally to 1,2-dimethylhydrazine (DMH)-induced rats for 16 weeks. The cytotoxicity of both compounds was tested on Caco-2, CT26, and NIH/3T3 cells using the MTT method. The cell cycle, apoptosis, and reactive oxygen species (ROS) levels were analyzed through flow cytometry. X-gal staining was used to examine the compound's effect on senescence. Oral co-administration of CCA-1.1 or PGV-1 significantly suppressed the carcinogenic characteristics and symptoms of premalignant colon cancer relative to DMH-only and untreated groups. CCA-1.1 and PGV-1 administration did not affect the blood profile. CCA-1.1 and PGV-1 demonstrated great cytotoxicity on Caco-2 and CT26 cells, with 50% inhibition concentration (IC50) values of 4.3 ± 0.2 and 3.1 ± 0.1 μM for CCA-1.1 and 11.2 ± 1.1 and 4.8 ± 0.1 μM for PGV-1, respectively, while not toxic against fibroblast cells. Both compounds instigated G2/M arrest and efficiently induced cell senescence and apoptosis. Moreover, these analogs selectively elevated oxidative stress in colon cancer cells without inducing noticeable changes in fibroblasts. In conclusion, PGV-1 and CCA-1.1 suppressed colorectal tumor formation and induced mitotic arrest.
Databáze: Directory of Open Access Journals
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