Bendamustine HCl is an alkylating agent associated with DNA damage with IC50 of 50 μM [1].

It has been reported that bendamustine is activated under DNA damage stress and apoptosis. Bendamustine inhibits mitotic checkpoints and induces mitotic catastrophe by inhibiting several mitosis-related genes such as Polo-like kinase 1, Aurora kinase A, and Cyclin B1 [1]. In myeloma cell lines, bendamustine induced apoptosis by cleavage of caspase 3, and resulted in G2 cell cycle arrest [2]. In chronic lymphocytic and mantle cell lymphoma cell lines, bendamustine HCL has been shown to activate both the mitochondrial cell death pathway and caspase-dependent apoptosis. Some assays showed that bendamustine exhibited anti-proliferation effects on dexamethasone-sensitive (MM1.S) and -resistant (MM1.R) multiple myeloma cells in a dose-dependent manner, with IC50s of 119.8 μM (MM1.S) and 138 μM (MM1.R), respectively. The apoptosis by activation of caspase-3 and caspase-8 was induced in both MM1.S and MM1.R cell lines [4].

References:
[1]. Leoni LM, Bailey B, Reifert J, Bendall HH, Zeller RW, Corbeil J, Elliott G, Niemeyer CC. Bendamustine (Treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylating agents. Clin Cancer Res. 2008 Jan 1;14(1):309-17.
[2]. Gaul L, Mandl-Weber S, Baumann P, Emmerich B, Schmidmaier R. Bendamustine induces G2 cell cycle arrest and apoptosis in myeloma cells: the role of ATM-Chk2-Cdc25A and ATM-p53-p21-pathways. J Cancer Res Clin Oncol. 2008 Feb;134(2):245-53.
[3]. Roué G, López-Guerra M, Milpied P, Pérez-Galán P, Villamor N, Montserrat E, Campo E, Colomer D. Bendamustine is effective in p53-deficient B-cell neoplasms and requires oxidative stress and caspase-independent signaling. Clin Cancer Res. 2008 Nov 1;14(21):6907-15.
[4]. Cai B, Wang S, Huang J, Lee CK, Gao C, Liu B. Cladribine and bendamustine exhibit inhibitory activity in dexamethasone-sensitive and -resistant multiple myeloma cells. Am J Transl Res. 2013;5(1):36-46.