Distinctive molecular signaling in triple-negative breast cancer cell death triggered by hexadecylphosphocholine (miltefosine).

Krittalak Chakrabandhu (1) , Sébastien Huault (1) , Anne-Odile Hueber (1)

1 IBDC - Institut de signalisation, biologie du développement et cancer - Institute of Developmental Biology and Cancer

This study describes the molecular signaling involved in the different cell death modes of triple-negative breast cancer cells induced by hexadecylphosphocholine (HePC/miltefosine), a clinically relevant anticancer alkylphosphocholine. We found that the HePC treatment triggers cell-type-dependent apoptotic and non-apoptotic cell death processes. Moreover, the expression level of the apoptosis activator Fas, and Fas/Fas ligand signaling capacity are not attributing factors for the preference toward apoptosis. Using Fas siRNA and overexpression approaches we establish that Fas is not a pro-apoptotic factor but a contributor to cell protection in HePC-apoptosis-sensitive cells. The insight in the multi-modal anticancer capability of HePC in triple-negative breast cancer cells may facilitate the targeted design of therapeutic strategies against triple-negative breast cancers.

Domaines: Biologie du développement

Krittalak Chakrabandhu, Sébastien Huault, Anne-Odile Hueber. Distinctive molecular signaling in triple-negative breast cancer cell death triggered by hexadecylphosphocholine (miltefosine).. FEBS Letters, 2008, 582 (30), pp.4176-84. ⟨10.1016/j.febslet.2008.11.019⟩. ⟨hal-00349454⟩