Fumitremorgin C (FTC) is the simplest member of Fumitremorgin family. It was isolated from the fungus Aspergillus Fumigatus by Cole and coworkers in 1977. Fumitremorgin C is a chemo sensitizing agent, a potent and sensitive pharmacological tool. Reverses multidrug resistance in several tumor cell lines. Research with breast cancer cell lines has provided evidence and also given insight into mechanism of action of Fumitremorgin C.
In breast cancers S1-M1-3.2 cell line overexpresses BCRP mRNA (Breast Cancer Resistance Protein). This is a membrane embedded protein, which acts as a drug efflux pump and prevents accumulation of cytotoxic agents (anticancer therapeutic agents) from reaching lethal levels in the cells. Mechanism of Action of Fumitremorgin C: It resensitizes the drug resistant cells by inhibiting BCRP-mediated drug transport. However, other mechanisms of resistance also exist in the drug selected cells, including alterations in topoisomerase activity, and FTC may overcome resistance through these mechanisms.
In Globlastoma multiforme a subset of tumor cells display stem cell like characteristics:
- The self-renewal ability.
- Expression of stem cell markers
These cells rely on the activity of ATP-Binding Cassette Transporter called ABCG2. ABCG2 increases the cells drug efflux capability, thereby conferring multidrug resistance to tumor cells. Both mice and human glioma cell lines present overexpression of ABCG2. Fumitremorgin C inhibits and reverses the activity of ABCG2.
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