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

Febri Wulandari; Muthi Ikawati; Sitarina Widyarini; Mitsunori Kirihata; Dhania Novitasari; Jun-Ya Kato; Edy Meiyanto

doi:10.4103/JAPTR.JAPTR_315_23

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

J Adv Pharm Technol Res. 2023 Oct-Dec;14(4):317-324. doi: 10.4103/JAPTR.JAPTR_315_23. Epub 2023 Oct 30.

Authors

Febri Wulandari¹, Muthi Ikawati^{1

2}, Sitarina Widyarini³, Mitsunori Kirihata⁴, Dhania Novitasari^{1

5}, Jun-Ya Kato⁵, Edy Meiyanto^{1

2}

Affiliations

¹ Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta.
² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta.
³ Department of Pathology, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta.
⁴ Research Center for Boron Neutron Capture Therapy, Osaka Metropolitan University, Osaka, Japan.
⁵ Laboratory of Tumor Cell Biology, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan.

Abstract

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.

Keywords: 1,2-dimethylhydrazine-induced rats; chemopreventive; colorectal cancer cells; curcumin analogs.