Differential Inhibition of Human Cancer Cell Proliferation by Citrus Limonoids

Abstract

Limonoids have been shown to inhibit the growth of estrogen receptor-negative and -positive human breast cancer cells in culture. The primary objective of this study was to test the antiproliferative activity of limonoids (obacunone 17 beta-D-glucopyranoside, nomilinic acid 17 beta-D-glucopyranoside, limonin, nomilin, and a limonoid glucoside mixture), found in high concentrations in mandarin (Citrus reticulata Blanco), against a series of human cancer cell lines. The human cancer cell lines included leukemia (HL-60), ovary (SKOV-3), cervix (HeLa), stomach (NCI-SNU-1), liver (Hep G2), and breast (MCF-7). The growth-inhibitory effects of the four limonoids and the limonoid glucoside mixture against MCF-7 cells were significant, and the antiproliferative activity of the different citrus limonoids was also dose and time dependent. No significant effects were observed on growth of the other cancer cell lines treated with the four individual limonoids at 100 micrograms/ml. At 100 micrograms/ml, the limonoid glucoside mixture demonstrated a partial inhibitory effect on SKOV-3 cancer cells. With use of flow cytometry, it was found that all the limonoid samples could induce apoptosis in MCF-7 cells at relatively high concentrations (100 micrograms/ml). Considering the high concentration needed to induce apoptosis, it is unlikely that this is the primary mechanism of action for the cytotoxic effects seen with limonoids in this study. Further work is needed in this area to establish the mechanism of action of citrus limonoids on human breast cancer cells.

Grapefruit Juice Suppresses Azoxymethane-induced Colon Aberrant Crypt Formation and Induces Antioxidant Capacity in Mice

“…In this field, various reports with grapefruit juice (GJ) both in vivo and in vitro have shown a clear antigenotoxic effect on the DNA and chromosomes damaged by mutagens with different mechanisms of action (Alvarez-González et al, 2004;Miyata et al, 2004;Razo-Aguilera et al, 2011). Besides, in the area of carcinogenesis, in vitro studies conducted on MCF-7 human breast cancer cells, or in Caco-2 and HL-60 cells support the idea that components of grapefruit (limonin and naringenin) have apoptotic activity that limits the growing of cancerous cells; also, the capacity to inhibit the development of cancer by grapefruit or because the activity of specific constituents have also been suggested in in vitro studies, as well as at the in vivo initiation or post-initiation stages (So et al, 1996;Tian et al, 2001;Kanno et al, 2005;Vanamala et al, 2006;Miller et al, 2008;Hwang et al, 2010). The findings obtained in these studies are in close agreement with the general suggestion that the consumption of fruits and vegetables reduces the risk of colon cancer (Koushik et al, 2007).…”

Citrus (Rutaceae): A Review of Recent Advances in Etymology, Systematics and Medical Applications

“…Flavonoids, particularly flavonones from the hesperidia have been intensively studied for antioxidant, anticancer (e.g. breast cancer - Tian et al, 2001), antiviral and anti-inflammatory activities, effects on capillary fragility and an observed inhibition of human platelet aggregation. Commercially valuable flavonoid-based industrial products are the anti-sweetening agents, hesperidin and naringin and their byproducts (Licandro & Olio, 2002: 170) -used in some tonic water for example.…”

Lepidotrichilins A and B, New Protolimonoids with Cytotoxic Activity from Trichilia Lepidota (Meliaceae)

“…Other studies on limonoids showed that these compounds were able to reduce cell viability and induce apoptosis in some cancer cells. Tian et al showed that four isolated limonoids from Citrus reticulata induced cell death by apoptosis in breast cancer cell line (MCF-7) [17]. Additionally neuroblastoma cell culture was shown to die by apoptosis when incubated with limonoids isolated from Citrus [8].…”