# The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM

## TL;DR

Forskolin, a natural compound, enhances the effectiveness of dexamethasone in killing myeloma cells by increasing apoptosis through BIM.

## Contribution

Forskolin synergizes with dexamethasone to induce cell death in myeloma via BIM, offering a potential treatment strategy.

## Key findings

- Forskolin potentiated the killing of MM cells when combined with various drugs, including dexamethasone.
- BIM was identified as a key mediator of the synergistic apoptosis induced by forskolin and dexamethasone.
- Forskolin maintained cell death at lower concentrations of conventional agents, suggesting reduced side effects.

## Abstract

We have previously demonstrated that activation of the cyclic adenosine monophosphate (cAMP) pathway kills multiple myeloma (MM) cells both in vitro and in vivo. In the present study we have investigated the potential of enhancing the killing of MM cell lines and primary MM cells by combining the cAMP-elevating compound forskolin with the commonly used MM therapeutic drugs melphalan, cyclophosphamide, doxorubicin, bortezomib and dexamethasone. We observed that forskolin potentiated the killing induced by all the tested agents as compared to treatment with the single agents alone. In particular, forskolin had a synergistic effect on the dexamethasone-responsive cell lines H929 and OM-2. By knocking down the proapoptotic BCL-2 family member BIM, we proved this protein to be involved in the synergistic induction of apoptosis by dexamethasone and forskolin. The ability of forskolin to maintain the killing of MM cells even at lower concentrations of the conventional agents suggests that forskolin may be used to diminish treatment-associated side effects. Our findings support a potential role of forskolin in combination with current conventional agents in the treatment of MM.