V.I. Kiselev (1), V.Yu. Alakhov (2), A.B. Semov (2), L.V. Iourtchenko (2), Liu Lin Fang (2), Li Shengmin (2), Xu Yan (2), Su Xiaoxue (2), E.L. Muyzhnek (3), M.A. Paltsev (1)
1 -National Research Center «Kurchatov Institute», Moscow, Russia
2 -Supratek Pharma Inc., Montreal, Canada
3 -ZAO «MiraxBioPharma», Moscow, Russia

There is a growing body of evidence confirming the validity of the concept of cancer stem cells (CSCs). It is becoming increasingly obvious that CSCs, possessing higher tumorigenicity, metastasis-initiating activity and chemoresistance, are a source of tumor growth, including the development of recurrences and metastases. In this regard, there is an urgent need to identify new non-toxic compounds that selectively act on CSCs. We have been the first to discover 3,3'-diindolylmethane (DIM) to be a selective and potent inhibitor of CSCs, cultured in serum-free medium as tumor spheroids. Treatment with DIM helped to overcome chemoresistance of CSCs to conventional cytotoxic drugs. Pre-incubation of tumor spheroids with DIM, which preceded the implantation into syngeneic mice significantly retarded the development of primary tumor foci and increased the survival of animals compared with control. With the use of innovative nanobiotechnological approaches we have developed two drug formulations in which bioavailability of DIM has been significantly increased compared with the crystalline DIM, and with the only formulated analogue – drug BioResponse-DIM (BR-DIM). This allows realize to the fullest degree the phenomenal therapeutic potential of this active substance.
cancer stem cells, 3, 3'-diindolylmethane, Tranilast, targeted anti-cancer therapy