Apoptosis and metastasis inhibitory potential of pineapple vinegar against mouse mammary gland cells in vitro and in vivo

Abstract

Background Plant-based food medicine and functional foods have been consumed extensively due to their bioactive substances and health-beneficial effects. Vinegar is one of them due to its bioactivities, which confers benefits on human body. Our previous study has produced pineapple vinegar that is rich in gallic acid and caffeic acid via 2 steps fermentation. There are many evidences that show the effectiveness of these resources in inhibiting the proliferation and metastasis of the cancer cells through several mechanisms. Methods Freeze-dried pineapple vinegar was evaluated for its in vitro apoptosis and metastasis inhibitory potential using MTT, cell cycle, Annexin V and scratch assays. The in vivo test using BALB/c mice challenged with 4 T1 cells was further investigated by pre-treating the mice with 0.08 or 2 ml/kg body weight of freshly-prepared pineapple vinegar for 28 days. The tumor weight, apoptotic state of cells in tumor, metastasis and immune response of the untreated and pineapple vinegar treatment group were evaluated and compared. Results From the in vitro study, an IC 50 value of 0.25 mg/mL after 48 h of treatment was established. Annexin V/PI and scratch closure assays showed that pineapple vinegar induced 70% of cell population to undergo apoptosis and inhibited 30% of wound closure of 4 T1 cells. High concentration of pineapple vinegar (2 ml/kg body weight) led to the reduction of tumor weight and volume by 45%as compared to the untreated 4 T1-challenged mice. This effect might have been contributed by the increase of T cell and NK cells population associated with the overexpression of IL-2 andIFN-γ cytokines and splenocyte cytotoxicity. Furthermore, fewer instances of metastasis events were recorded in the pineapple vinegar treatment group and this could be explained by the downregulation of inflammation related genes (iNOS, NF-kB and COX2), metastasis related genes (iCAM, VEGF and MMP9) and angeogenesis related genes (CD26, TIMP1, HGF, MMP3, IGFBP-1 and IGFBP-2). Conclusion The ability of pineapple vinegar to delay cancer progression portrayed its potential as chemopreventive dietry intervention for cancer therapy. Electronic supplementary material The online version of this article (10.1186/s12986-019-0380-5) contains supplementary material, which is available to authorized users.

Therapeutic Potential of Plant Phenolic Acids in the Treatment of Cancer

“…Interestingly, 70 % of cell population underwent apoptosis and 30 % inhibited wound closure of 4T1 cells in response to the administration of PV. Therefore, anti-cancer efficacy of pineapple vinegar may be associated with the presence of phenolic acids, especially GA and CA in high content [65]. Moreover, methanol extracts of Anchusa azurea Mill, with CA as one of the four most abundant compounds, was found to induce programmed cell death in cancer cell line via activation of capsase-3/7 and -9 as well as modulation of cytoskeleton dynamics [66].…”

Anticancer effects of enrichment in the bioactive components of the functional beverage of Turkish gastronomy by supplementation with purple basil (Ocimum basilicumL.) and the ultrasound treatment

“…AO: acridine orange; PI: propidium iodide development of colon carcinogenesis induced by azoxymethane was inhibited. Similarly,Mohamad et al (2019) indicated the potential anticancer activities of freeze-dreed coconut water vinegars in breast cancer cell model (4T1) as in vitro and in mice with breast cancer as in vivo. Accordingly, that study was pointed out that coconut water vinegars caused delay in breast tumor development by inducing apoptosis and also increasing in the inhibition of cell proliferation in 4T1.…”

Induction of Apoptosis and Regulation of MicroRNA Expression by (2E,6E)-2,6-bis-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone (BHMC) Treatment on MCF-7 Breast Cancer Cells

“…Cell apoptosis assay was conducted based on a study method [ 44 ] with some changes. Apoptosis of control and BHMC-treated MCF-7 cell was evaluated using AnnexinV-FITC/PI apoptosis detection kit (Becton Dickinson, USA).…”