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Abstract

Sanguinarine, a benzophenanthridine alkaloid, has anticancer potential through induction of cell death. We previously demonstrated that sanguinarine treatment at a low level induced apoptosis or programmed cell death (PCD) in the Bcl-2 low-expressing K562 human erythroleukemia cells, and that a high level induced blister cell death (BCD); whereas Bcl-2 overexpressing, sanguinarine-treated JM1 pre-B lymphoblastic cells displayed neither apoptosis nor BCD morphologies. Here, we report that sanguinarine-treated K562 cells, when analyzed by western blot, showed significant increase in expression of the pro-apoptotic Bax protein in apoptosis, but not in BCD. cDNA expression array of PCD in K562 cells failed to reveal the presence of Bax at the gene transcript level, which suggests that this cell death process does not require de novo protein synthesis. Treated JM1 cells, on the other hand, showed an increase in the expression of Bcl-2 protein in both forms of cell death, but failed to show Bax expression. The role of other members of the Bcl-2 family remained negligible. Caspase-3 activation was observed in apoptosis of K562 cells but not in BCD or in sanguinarine-treated JM1 cells. These results suggest that sanguinarine in K562 cells induces apoptosis through increasing Bax and activating caspase-3, whereas sanguinarine-induced BCD involves neither. These results also suggest that in JM1 cells, Bcl-2 may play a role in susceptibility of cells to induction of apoptosis and BCD.

Oncolytic Group B Adenovirus Enadenotucirev Mediates Non-apoptotic Cell Death with Membrane Disruption and Release of Inflammatory Mediators

“…Cisplatin also induced death with features of apoptosis. In contrast, cells treated with EnAd and Ad11p usually clumped together, showed little evidence of apoptosis, and underwent sudden formation of large single membrane blisters at the time of death 9 (Movies S1, S2, S3, S4, and S5). This dramatic cellular demise, termed single blister cell death (BCD) is a typical marker of cell death by oncosis10, 11 and is thought to reflect loss of control over ion transport and consequent osmotic rupture.…”

Sanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling

“…Consequently, we observed that treated MM cells presented an increase in cytochrome c levels in their cytosolic fraction and a concomitant loss in their mitochondrial fraction. One of the functions of cytosolic cytochrome C is to interact with apoptotic protease-activating factor-1 (APAF-1) and procaspase 9 in the presence of ATP to form the multimeric complex, apoptosome, which in turn activates caspase 9 and induce apoptosis (34). Since we show that caspase 9 expression was efficiently increased in MM cells in response to SNG treatment, we suggest that SNG-mediated apoptosis in MM cell lines involves mitochondria-mediated caspase activity.…”

Toxicological Effects of Berberine and Sanguinarine

“…In similarity to berberine, sanguinarine also have antimicrobial, antioxidant and anti-inflammatory properties (Firatli et al, 1994 ). The cytotoxic and cytostatic effects of sanguinarine on a variety of human cancer cells, including human epidermoid carcinoma, erythroleukemia, prostate cancer, pancreatic carcinoma, colon cancer, breast cancer, lung cancer, promyelocytic leukemia, and bone cancer (Weerasinghe et al, 2001a , b ; Matkar et al, 2008 ; Vrba et al, 2009 ; Park et al, 2010 ), have been reported. Sanguinarine exhibits the highest cytotoxicity among benzophenanthridine alkaloids (Slaninová et al, 2001 ; Vogel et al, 2010 ).…”