Subchronic toxicity, immunoregulation and anti-breast tumor effect of Nordamnacantal, an anthraquinone extracted from the stems of Morinda citrifolia L

Abstract

BackgroundMorinda citrifolia L. that was reported with immunomodulating and cytotoxic effects has been traditionally used to treat multiple illnesses including cancer. An anthraquinone derived from fruits of Morinda citrifolia L., nordamnacanthal, is a promising agent possessing several in vitro biological activities. However, the in vivo anti-tumor effects and the safety profile of nordamnacanthal are yet to be evaluated.MethodsIn vitro cytotoxicity of nordamnacanthal was tested using MTT, cell cycle and Annexin V/PI assays on human MCF-7 and MDA-MB231 breast cancer cells. Mice were orally fed with nordamnacanthal daily for 28 days for oral subchronic toxicity study. Then, the in vivo anti-tumor effect was evaluated on 4T1 murine cancer cells-challenged mice. Changes of tumor size and immune parameters were evaluated on the untreated and nordamnacanthal treated mice.ResultsNordamnacanthal was found to possess cytotoxic effects on MDA-MB231, MCF-7 and 4T1 cells in vitro. Moreover, based on the cell cycle and Annexin V results, nordamnacanthal managed to induce cell death in both MDA-MB231 and MCF-7 cells. Additionally, no mortality, signs of toxicity and changes of serum liver profile were observed in nordamnacanthal treated mice in the subchronic toxicity study. Furthermore, 50 mg/kg body weight of nordamncanthal successfully delayed the progression of 4T1 tumors in Balb/C mice after 28 days of treatment. Treatment with nordamnacanthal was also able to increase tumor immunity as evidenced by the immunophenotyping of the spleen and YAC-1 cytotoxicity assays.ConclusionNordamnacanthal managed to inhibit the growth and induce cell death in MDA-MB231 and MCF-7 cell lines in vitro and cease the tumor progression of 4T1 cells in vivo. Overall, nordamnacanthal holds interesting anti-cancer properties that can be further explored.

Morinda citrifolia noni water extract enhances innate and adaptive immune responses in healthy mice, ex vivo, and in vitro

“…Numerous papers have reported that extract or juice from fruit of noni is able to modulate functional role of immune cells such as NK cells, CD4 + T‐cells, CD8 + T‐cells, and B‐cells under disease conditions such as the tumor xenograft model, Leishmania amazonensis infection model, paw and ear edema model, picryl chloride‐induced contact dermatitis model, 12‐O‐tetradecanoylphorbol‐13‐acetate‐induced inflammation model, alcohol‐induced liver damage model, 12‐O‐tetradecanoylphorbol‐13‐acetate‐induced skin inflammation model, and DSS‐induced colitis model (Abu et al, ; Akihisa et al, ; Almeida‐Souza et al, ; Almeida‐Souza et al, ; Chang et al, ; Coutinho de Sousa et al, ; Li et al, ; Lim et al, ; Murata et al, ). In this study, however, we investigated the in vivo immunostimulatory activity of Mc‐eWE using mice under normal conditions, because we were curious on the immunoregulatory activity of noni fruit extract under healthy conditions.…”

Properties and Applications of Morinda citrifolia (Noni): A Review

“…The biological activity of the nordamnacanthal extracted from the stems of M. citrifolia was also checked in vitro by Abu et al. () using MTT assay, cell cycle and Annexin V/PI assays on human MCF‐7, MDA‐MB231, and 4T1 breast cancer cells. The results showed that nordamnacanthal extracted from the stems of M. citrifolia managed to reduce the viability of MCF‐7, MDA‐MB231, and 4T1 cells in a dose‐dependent manner as a higher concentration of nordamnacanthal reduced a higher degree of the viability for all the tested breast cancer cells.…”

Evaluation of Subchronic Toxicity of Lactobacillus Paracasei Hii03 Fermented Morinda Citrifolia (Noni) Fruit Juice

“…ND intervention does not cause any mortality and diminishes the development of 4T1 in mice. The results suggested that ND supplementation enhanced the immunity without any adverse effects [24].…”

“…Even though noni and its products were reported for beneficial effects, some of the controversial reports also are there [18,19]. Some studies evaluated the subchronic toxicity of various part of noni plant extracts [20][21][22][23][24]. There was no literature on safety and subchronic toxicity of fermented noni fruits.…”