Cajanol: The role of phytoestrogen in cancer cells

Cajanol in cancers

Cajanol (5-hydroxy-3-(4-hydroxy-2-methoxyphenyl)-7-methoxychroman-4-one) is an isoflavanone from Pigeonpea (Cajanus cajan)roots. It is the most active phytoalexin in pigeon pea, with a chemical struture of C17H16O6. Cajanol belongs to the group of isoflavonoids with methoxy group C7 of the isoflavonoid backbone.

Benefits of cajanol in cancer cell inhibition

Cajanol is beneficial to the body. It has been proved to exert anti-tumor and anti-carcinogenesis to cancer cells. It is also a strong antibacterial compounds against both gram negative and gram positive bacteria.

Mechanism of action of Cajanol

There are several biochemical pathways by which Cajanol exert its action against cancer cells and bacteria. In this article, you will learn the mechanism of action of Cajanol against several cancer cell lines. You will also learn about the inhibitory action of Cajanol against both gram negative and gram positive bacteria.

Cajanol in breast cancer

In human breast cancer experiments, cajanol has been shown to inhibit MCF-7 cells. MCF-7 is a human breast cancer cell line with estrogen, progesterone and glucocorticoid receptors. It is said to be derived from the pleural effusion of a 69 years old Caucasian metastatic breast cancer (adenocarcinoma) in 1970 by Dr Soule of the Michigan Cancer Foundation, Detroit, MI.

Cajanol is similar to mammalian estrogens. It exerts its inhibitory role in E2-induced MCF-7 proliferation by interacting directly with estrogen receptors. Cajanol also have the ability to arrest the cell cycle in the G2/M phase and have also induced apoptosis via a reactive oxygen species (ROS)-mediated mitochondria- dependent pathway.

In Prostate cancer

Prostate cancer is the leading cause of cancer related deaths in men. It develops mainly in men of age 65 or older. It is rare among men of age below 40, and is commonly referred to as hormone-dependent cancer, because sex steroid hormones control the initiation and progression of prostate cancer.

Estrogen plays important role in prostate cancer pathogenesis. According a study on aromatase knockout mice, which cannot metabolize androgens to estrogens, high testosterone levels led prostatic hyperplasia. In contrast, high estrogen and low testosterone levels induce inflammatory events and premalignant lesions. As a man grows older, the production of testosterone decreases which estrogen level remains constant. This leads to a high estradiol/testosterone ratio, and thus leads to premalignant lesions.

E2 is the human endogenous estrogen and known to be the most active estrogen receptor agonist. To inhibit the proliferation of prostate cancer, the phytoestrogen competes effectively with E2 for the receptor sites, thus inhibiting E2-induced proliferation of PC-3 prostate cancer cells.

Cajanol modulates PC-3 cell proliferation via ERα-associated PI3K signal-regulated pathways. By interfering with ERα-associated PI3K pathway, cajanol inhibited the survival and proliferation of estrogen-responsive cells following a process that could be independent of the nuclear functions of the ERα. This is followed by the activation of effectors GSK3 and cyclin D1, and then, these cascade reactions results in cell cycle arrest and the final apoptosis.

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References

Ken LC, Qian W, Sarah O, et al. 2010. Non-nuclear estrogen recep-tor asignaling promotes cardiovascular protection but notuterine or breast cancer growth in mice. J Clin Invest 120(7):2319–2330.

Luo M, Liu X, Zu YG, et al. 2010. Cajanol, a novel anticancer agentfrom Pigeonpea [Cajanus cajan (L.) Millsp.] roots, induces apop-tosis in human breast cancer cells through a ROS-mediatedmitochondrial pathway. Chem Biol Interact 188: 151–160.

Liang, Lu & Gao, Chang & Luo, Meng & Zhao, Chunjian & Wang, Yi & gu, Chengbo & Jinghua, Yu & Fu, Yujie. (2013). The Phytoestrogenic Compound Cajanol from Pigeonpea Roots is Associated with the Activation of Estrogen Receptor α-dependent Signaling Pathway in Human Prostate Cancer Cells. Phytotherapy research : PTR. 27. 10.1002/ptr.4937.

Ellem SJ, Risbridger GP. Aromatase and regulating the estrogen: androgen ratio in the prostate gland. J Steroid Biochem Mol Biol (2010) 118:246–51. doi:10.1016/j.jsbmb.2009.10.015