Arsenic trioxide induces programmed cell death through stimulation of ER stress and inhibition of the ubiquitin–proteasome system in human sarcoma cells

Anticancer metal drugs and immunogenic cell death

“…This is surprising as multiple metal complexes including arsenic [78,79], iron [80], ruthenium [81], gold [82], copper [83][84][85], osmium [86], and iridium [87] compounds have been demonstrated to activate some hallmarks of ICD including ROS production and UPR as well as ER stress [59]. Thus we conclude that a systematic re-evaluation of promising experimental metal-containing anticancer compounds in an immunogenic environment is urgently needed.…”

“…In this context, CD47-blocking antibodies can also be considered potential factors to be used in ICD combinatorial strategies. Taking into account the broad involvement of ROS-mediated processes and ER stress in the mode-of-action of multiple experimental anticancer metal drugs mentioned above [64,78,79,[81][82][83][84][85][86][87], some of these compounds might also act as ICD adjuvants.…”

Induction of apoptosis via proteasome inhibition in leukemia/lymphoma cells by two potent piperidones

“…Inhibition of the proteasome affects the ubiquitin-proteasome pathway (UPP) leading to the accumulation of misfolded and unfolded proteins [19, 20]. This, in turn, causes proteotoxic stress within the endoplasmic reticulum (ER), which leads to activation of the unfolded protein response (UPR) [20, 21]. Thus, when the proteasome is inhibited, cancer cells become overloaded with UPR stress, which ultimately results in apoptosis [20–22].…”

Arsenic induced complete remission in a refractory T-ALL patient with a distinct T-cell clonal evolution without molecular complete remission: A case report

“…ATO has been demonstrated to selectively inhibit growth and induce apoptosis in several cell lines, including the megakaryocytic leukemia cell lines HEL, Meg-01, UT7, and M07e (32), the myeloid leukemia cell lines U937 and KG-1, plasma cells and cell lines from myeloma patients (33) and B cell leukemia cell lines (34). Notably, ATO has been demonstrated to be capable of inducing apoptosis in certain solid tumor cells, for example non-small cell lung cancer cells and sarcoma cells (35,36), demonstrating the broad antitumor activity of arsenic. Due to a lack of effective treatments against adult T-cell leukemia/lymphoma (ATLL), ATO activity was also tested in vitro in several HTLV-1-infected cell lines.…”