Growth inhibitory effects of crude pomegranate peel extract on chronic myeloid leukemia, K562 cells

Abstract

Background:Pomegranate (Punica granatum) is currently a member of Lythraceae family which has potentially cytotoxic activities. Numerous studies have been done on cytotoxic components of pomegranate's juices, barks and leaves. The peels, which considered as a waste, contain higher antioxidant components compared with other parts of the plant.Aim:To investigate the potential anti-cancer activity of pomegranate peel on growth and cell death mechanisms of chronic myeloid leukemic (CML) cells, K562.Materials and Methods:Punica granatum peels extract (PGPE) was extracted by successive ethanol extraction, 80% (v/v), freeze dried, diluted to 20 mg/mL working concentration and was subjected to phytochemical screening. K562 cell was treated with crude PGPE for 72 h. Following IC50 concentration, the apoptosis, cell cycle and protein analysis were evaluated. Cell growth inhibition assay was performed by conventional trypan blue exclusion assay. Apoptosis and cell cycle were analyzed by flow-cytometry using BD apoptosis and cell cycle kits and protein analysis by western blotting. All the results are expressed as mean ± standard error of mean of three independent experiments. Statistical analysis was performed by nonparametric Mann-Whitney U-test.Results:Results demonstrated that PGPE promotes growth inhibition of K562 cells mainly via G2/M phase arrest while still conserving apoptosis induction, but at a lower rate. Apoptosis activities were proposed by the up-regulation of caspases and cytochrome c with an elevated level of p21 and p53.Conclusion:PGPE caused an inhibition in cell proliferation of CML cell mainly by cell cycle arrest.

Characterization of pomegranate peel extracts obtained using different solvents and their effects on cell cycle and apoptosis in leukemia cells

“…Otherwise, another study observed a cell cycle arrest in a different cell cycle phase (G2/M) when using pomegranate peel extract obtained by another extraction method in a different cell line (K562 cells) (Asmaa et al, 2015). Besides that, the S phase is one of the targets of several anticancer drugs to reduce the proliferation of tumor cells, such as methotrexate, pralatrexate, 7-Hydroxystaurosporine (UCN-01), etoposide, and many others (Shapiro & Harper, 1999;Tazawa et al, 2014;Wood & Wu, 2015).…”

“…Pomegranate has shown potential in the treatment of several tumors by inhibition of proliferation in colon, breast, lung, pancreatic, and prostate cancer cells in vitro (Adhami et al, 2009;Panth, Manandhar, & Paudel, 2017). However, few studies have investigated the potential of pomegranate, let alone its peel extracts, for the treatment or prevention of leukemia (Asmaa, Ali, Farid, & Azman, 2015;Dahlawi, Jordan-Mahy, Clench, & Le Maitre, 2012;Dahlawi, Jordan-Mahy, Clench, McDougall, & Maitre, 2013).…”

“…Most of the scientific reports regarding pomegranate and cancer have focused on the edible parts of the fruit (seeds and juice). Recently, it has been given more attention to its nonedible parts, such as peels, leaves, flowers, barks, and roots (Akhtar, Ismail, Fraternale, & Sestili, 2015;Asmaa et al, 2015;El-Hadary & Ramadan, 2019;Fischer, Carle, & Kammerer, 2011;Li et al, 2016;Song, Li, & Li, 2016). The pomegranate peel is considered byproduct for food and beverage industries even though it has been shown to display greater antioxidant activity than the edible parts of the fruit (Fischer et al, 2011;Yunfeng Li et al, 2006).…”

Deciphering the Molecular Mechanism Underlying the Inhibitory Efficacy of Taiwanese Local Pomegranate Peels against Urinary Bladder Urothelial Carcinoma

“…In addition to the above cancer cells, Asmaa et al (2015) reported that the treatment of 80% ethanol extract of pomegranate peels (PGPE) mainly evokes G 2 /M cell cycle arrest to inhibit chronic myeloid leukemia K562 cells [ 24 ]. The compounds present in pomegranate peels possess inhibitory activities against prostate cancer.…”

Potential antitumor effects of pomegranates and its ingredients

“…Peels extract of pomegranates showed role in the promotion of growth inhibition of K562 cells mainly through G2/M phase arrest. [ 37 ] Result based on flow cytometry revealed that leaves extract affected H1299 cell survival through arresting cell cycle progression in G2/M phase and inducing apoptosis. [ 38 ] Result based on multiple myeloma cells confirmed that cytotoxic and apoptotic effects of extracts of pomegranates through disruption of mitochondrial membrane potential and increasing cell cycle arrest.…”