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Anticancer activity of vitamin D, genistein and indoloquinoline analogs

Joanna Wietrzyk 

Polish Academy of Sciences, Institute of Immunology and Experimental Therapy (IITD), Rudolfa Weigla 12, Wrocław 53-114, Poland


The natural products with various chemical structures have been identified as anticancer agents. Several potential lead molecules such as vincristine, vinblastine, camptothecin, taxol etc. have been isolated from plants and many of them have been modified to obtain compounds with optimal pharmacological properties. Among them, successful molecules like irinotecan, topotecan, teniposide, taxotere, etoposide, etc. have appeared as drugs after modification of natural leads. Therefore the studies concentrated on natural products from various sources are still intensive. Our studies were focused on two groups of plant derived compounds as well as on vitamin D derivatives. The first group represents isoflavones, such as genistein, which are phytochemicals found along with soy protein. They are supposed to be responsible for the low incidence of prostate, mammary gland and colon cancer in Asian countries. Another one plant derived phytochemical is configuration of indolo[2,3-b]quinoline which exist in nature as indole alkaloid – neocryptolepine. It was discovered in extract from African plant Cryptolepis sanguinolenta. This alkaloid possess, among others, cytotoxic and antimalaric activity. Synthetic analog of neocryptolepine - 5,11-dimetylo-5H-indolo[2,3-b]quinoline (DIMIQ)) is also structurally similar to elipticine – plant alkaloid with cytotoxic activity. On the other hand, serum active form of vitamin D3, 1,25-dihydroxyvitamin D3 (calcitriol) level is found to be inversely related to incidence of some cancers. Calcitriol levels are determined by skin exposure to ultraviolet light and, to a minor extent, nutritional uptake and subsequent conversion of the precursor vitamin D to the active hormone by the cytochrome P450 hydroxylases.

In our studies we evaluated the anticancer effect of series of analogs of these three natural compounds alone and in combined therapy with known anticancer agents in several mouse and human tumour models. In the course of these studies we selected lead compounds especially from the group of vitamin D analogs, which represents agents showing better anticancer activity with lowered toxicity in comparison to calcitriol. We also conducted the studies on its mechanisms of action.


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Related papers

Presentation: Invited oral at IX Multidyscyplinarna Konferencja Nauki o Leku, by Joanna Wietrzyk
See On-line Journal of IX Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2014-03-14 19:47
Revised:   2014-05-02 19:35