Luteolin : A Natural Fighter of Cancers

Luteolin : A Natural Fighter of Cancers

Luteolin (3',4',5,7-tetrahydroxyflavone) is a natural occuring flavonoid that exists in many plants including in their fruits, vegetables, and also in few medicinal herbs.

Vegetables and fruits such as celery, parsley, broccoli, onion leaves, carrots, green peppers, cabbages, apple skins, chamomile tea, olive oil, peppermint, rosemary and chrysanthemum flowers are luteolin rich [1,2]. Plants rich in luteolin have been used as Chinese traditional medicine for hypertension, inflammatory diseases, and cancer [3]. Luteolin and its glycosides are widely distributed in the plant kingdom; they are present in many plant families and have been identified in Bryophyta, Pteridophyta, Pinophyta and Magnoliophyta [4]. Flavonoids are have been beneficial to human as well as animal kingdom due to their important pharmacologically activities such as being antioxidants, estrogenic regulators, and/or antimicrobial agents [5]. Moreover, there are evidences that suggest that flavonoids may block several points in the progression of carcinogenesis, including cell transformation, invasion, metastasis, and angiogenesis, through inhibiting kinases, reducing transcription factors, regulating cell cycle, and inducing apoptotic cell death [5].

Interestingly, the pharmacological activities of luteolin could be functionally related to each other. For instance, the anti-inflammatory effect of luteolin also may be linked to its anticancer function. The anticancer property of luteolin is associated with inducing apoptosis, which involves redox regulation, DNA damage, and protein kinases in inhibiting proliferation of cancer cells and suppressing metastasis and angiogenesis. Furthermore, luteolin sensitizes a variety of cancer cells to therapeutically induced cytotoxicity through suppressing cell survival pathways and stimulating apoptosis pathways [6]. Likewsie, luteolin displays specific anti-inflammatory effects at micromolar concentrations which are only partly explained by its anti-oxidant capacities [7].

When compared to other flavonoids, luteolin was usually among the most effective ones, inhibiting tumor cell proliferation with IC₅₀ values between 3 and 50 µM in vitro and in vivo by 5 to 10 mg/kg i.p., intragastric application of 0.1-0.3 mg/kg/d, or as food additive in concentrations of 50 to 200 ppm. Luteolin has been shown to penetrate into human skin, making it also a candidate for the prevention and treatment of skin cancer [8]. Notably, luteolin is blood-brain barrier permeable, rendering it applicable to the therapy of central nerve system diseases, including brain cancer [9].

Epidemiological studies suggest that dietary intake of flavonoids is inversely associated with risk of lung, prostate, stomach, and breast cancer in humans [1]. However, there are few epidemiological reports designed to study the role of luteolin in cancer prevention. As more such studies will be reported a clearer image of luteolin, and its role as an anticancer and/or chemoprevention agent will emerge.

Researchers have formulated water soluble polymer-encapsulated Nano-luteolin from hydrophobic luteolin, and studied its anticancer activity against lung cancer and head and neck cancer. In vitro studies demonstrated that, like luteolin, Nano-luteolin inhibited the growth of lung cancer cells (H292 cell line) and squamous cell carcinoma of head and neck (SCCHN) cells (Tu212 cell line). In Tu212 cells, the IC₅₀ value of Nano-luteolin was 4.13 µM, and that of luteolin was 6.96 µM. In H292 cells, the IC₅₀ of luteolin was 15.56 µM, and Nano-luteolin was 14.96 µM [10].

Finally, in a recent study, luteolin was identified as the inhibitor of vaccinia-related kinase 1 (VRK1) by screening a small-molecule natural compound library [11]. Luteolin is also being considered as a potential cure for colorectal cancer [12].

Luteolin synthesis: Bull Korean Chem Soc 2012, 33(5), 1773-1776

References:

1. Neuhouser, M. L. Dietary flavonoids and cancer risk: evidence from human population studies. Nutr Cancer 2004, 50, 1-7.

2. Miean, K. H.; et. al. Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. J Agric Food Chem 2001, 49(6), 3106-3112.

3. Harborne, J. B.; et. al. Advances in flavonoid research since 1992. Phytochemistry 2000, 55, 481-504.

4. López-Lázaro M. Distribution and biological activities of the flavonoid luteolin. Mini Rev Med Chem 2009, 9(1), 31-59.

5. Birt, D. F.; et. al. Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacol Ther 2001, 90, 157-177.

6. Lin, Y.; et. al. Luteolin, a flavonoid with potentials for cancer prevention and therapy. Curr Cancer Drug Targets 2008, 8(7), 634-646.

7. Seelinger, G.; et. al. Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin. Planta Med 2008, 74(14), 1667-1677.

8. Seelinger, G.; et. al. Anti-carcinogenic effects of the flavonoid luteolin. Molecules 2008, 13(10), 2628-2651.

9. Wruck, C. J.; et. al. Luteolin protects rat PC12 and C6 cells against MPP+ induced toxicity via an ERK dependent Keap1-Nrf2-ARE pathway. J Neural Transm Suppl 2007, 72, 57-67.

10. Majumdar, D.; et. al. Luteolin nanoparticle in chemoprevention-in vitro and in vivo anticancer activity. Cancer Prev Res (Phila) 2014, 7(1), 65-73.

11. Kim, Y. S.; et. al. Luteolin suppresses cancer cell proliferation by targeting vaccinia-related kinase 1. PLoS One 2014, 9(10), e109655.

12. Pandurangan, A. K.; et. al. Luteolin, a bioflavonoid inhibits colorectal cancer through modulation of multiple signaling pathways: a review. Asian Pac J Cancer Prev 2014, 15(14), 5501-5508.