The pterocarpanquinone LQB 118 induces apoptosis in tumor cells through the intrinsic pathway and the endoplasmic reticulum stress pathway

Abstract

LQB 118 is a pterocarpanquinone compound synthesized by our group. It has already been shown that it acts against different leukemia cell lines. However, little is known about the pathway through which this compound induces the death of these cells. In this work, we analyzed the cell death process induced by LQB 118 in K562, a chronic myeloid leukemia cell line, and in Jurkat, a lymphoblastic acute leukemia cell line. For this, we carried out a cell viability assay by MTT, an apoptosis/necrosis assay through the annexin/propidium iodide label, cell cycle by flow cytometry, assessed changes in the mitochondrial membrane potential using DiOC6(3), cytoplasmic calcium analysis by Fluo-3-AM, and a caspase-9 and caspase-12 activity assay. We found that LQB 118 induced apoptosis in both cell lines, measuring caspase-12 and caspase-9 activation, phosphatidylserine externalization, and DNA fragmentation. The compound induced an increase in cytoplasmic calcium on both cell lines. However, the compound could only induce mitochondrial membrane depolarization on K562 cells. Our data show that LQB 118 may have potential therapeutic value for leukemia, being able to overcome multiple resistance mechanisms.

Pterocarpanquinone LQB-118 Induces Apoptosis in Leishmania (Viannia) braziliensis and Controls Lesions in Infected Hamsters

“…These results suggest LQB-118 induces mitochondrion-dependent apoptosis in Leishmania spp. On the other hand, LQB-118-induced apoptosis in tumor cells is believed to involve different routes, depending on the cell type: increasing ROS, intracellular calcium levels and the activity of caspase 9 or 12 [23] .…”

Towards Comprehension of the ABCB1/P-Glycoprotein Role in Chronic Myeloid Leukemia

“…Different pathways have been proposed to explain the mechanisms of action of LQB-118 in CML. de Sá Bacelar et al [ 143 ] investigated cell death induction by LQB-118 in a K562 cell line. In agreement with Maia et al [ 142 ], the authors confirmed the cytotoxic effect of LQB-118 on apoptosis induction.…”

“…Moreover, this compound induced an increase in reactive oxygen species (ROS) through its reduction at the mitochondria. Finally, the authors showed that LQB-118 induced time- and dose-dependent endoplasmic reticulum stress (ER) via the caspase-12 activation pathway [ 143 ]. The LQB-118 mechanism of action in CML cells was further studied by de Faria et al [ 144 ].…”

TIPE‑2 suppresses growth and aggressiveness of hepatocellular carcinoma cells through downregulation of the phosphoinositide 3‑kinase/AKT signaling pathway

“…Endoplasmic reticulum stress is implicated in the progression of human carcinoma via the regulation of apoptotic signaling pathways in tumor cells ( 41 ). Edagawa et al ( 42 ) indicated that endoplasmic reticulum stress induced sensitization of P53-deficient human colon cancer cells to TNF-related apoptosis-inducing ligand-mediated apoptosis via the upregulation of death receptor 5, which may further lead to tumor growth inhibition.…”