A standardized chamuangone enriched extract shows anticancer efficacy in allograft models of metastatic breast cancer

Chamuangone is a polyprenylated benzophenone found in the leaves of the Thai vegetable Garcinia cowa Roxb., which has been reported for its in vitro anticancer properties. The leaves have traditionally been used for the treatment of inflammation, infections, and diabetes. In this study, a standardized chamuangone-enriched extract (CEE) from G. cowa leaves, containing 73.0 ± 2.0 % w/w of chamuangone, was evaluated in vitro and in vivo in allograft models (4 T1-luc cells) of breast cancer (BC) and metastatic breast cancer (MBC). The effects of CEE on 4 T1-luc cell viability, apoptosis, cell cycle, and cell migration were analyzed using CCK-8, flow cytometry, and wound healing assays. The in vivo antitumor and antimetastatic efficacy of CEE at doses of 25, 50, and 100 mg/kg body weight (b.w.) was evaluated in BALB/c mice. Tumor markers (CEA, CA 125, CA 15–3), apoptotic markers (p53, Bcl-2), and inflammatory markers (MMP-2, MMP-9, IL-6, NF-κB, and TNF-α) were assessed using ELISA assays. Additionally, the pharmacokinetic and biodistribution profiles of CEE were assessed using the normal mice. The results revealed that CEE (10 µg/mL) decreased 4 T1-luc cell viability, with IC 50 values of 62.5, 48.07, and 31.18 μg/mL at 24, 48, and 72 h, respectively. CEE induced early apoptosis (18.38 %) and late apoptosis (42.79 %), inhibited cell migration and triggered cell cycle arrest, with 59.92 % of cells in the subG1 phase. Furthermore, CEE at 100 mg/kg b.w., significantly inhibited tumor growth and metastasis, in vivo and significantly modulating apoptotic, tumor, and inflammatory markers. The plasma half-life (t½) of CEE at 100 mg/kg b.w. was found to be 11 h. The liver achieved the maximum concentration of chamuangone, followed by the spleen, kidneys, lungs, and heart. Based on the preclinical safety assessment of CEE, a green extract, a dose of 100 mg/kg b.w. is considered safe for therapeutic application as a chemopreventive functional ingredient in BC treatment. • CEE decreased cell viability and induces apoptosis in 4 T1-luc cells. • CEE inhibited cell migration and induced cell cycle arrest in the sub-G1 phase. • CEE inhibited tumor growth and metastasis in allograft models of breast cancer. • CEE modulated apoptotic, tumor, and inflammatory markers, in vitro and in vivo . • CEE achieved a plasma half-life of 11 h and maximum concentration in the liver.