Bersavine: A Novel Bisbenzylisoquinoline Alkaloid with Cytotoxic, Antiproliferative and Apoptosis-Inducing Effects on Human Leukemic Cells

Abstract

Bersavine is the new bisbenzylisoquinoline alkaloid isolated from the Berberis vulgaris L. (Berberidaceae) plant. The results of cytotoxicity screening 48 h post-treatment showed that bersavine considerably inhibits the proliferation and viability of leukemic (Jurkat, MOLT-4), colon (HT-29), cervix (HeLa) and breast (MCF-7) cancer cells with IC50 values ranging from 8.1 to 11 µM. The viability and proliferation of leukemic Jurkat and MOLT-4 cells were decreased after bersavine treatment in a time- and dose-dependent manner. Bersavine manifested concentration-dependent antiproliferative activity in human lung, breast, ovarian and hepatocellular carcinoma cell lines using a xCELLigence assay. Significantly higher percentages of MOLT-4 cells exposed to bersavine at 20 µM for 24 h were arrested in the G1 phase of the cell cycle using the flow cytometry method. The higher percentage of apoptotic cells was measured after 24 h of bersavine treatment. The upregulation of p53 phosphorylated on Ser392 was detected during the progression of MOLT-4 cell apoptosis. Mechanistically, bersavine-induced apoptosis is an effect of increased activity of caspases, while reduced proliferation seems dependent on increased Chk1 Ser345 phosphorylation and decreased Rb Ser807/811 phosphorylation in human leukemic cells.

Disease Modifying Osteoarthritis Drug Discovery Using A Temporal Phenotypic Reporter In 3D Aggregates of Primary Human Chondrocytes

“…Another study showed weak anti-microbial activity against Plasmodium falciparum with low cytotoxicity in the KB cell line 42 . Although there is little published research on aromoline, various bisbenzylisoquinoline alkaloids are being studied for their anti-proliferative, anti-inflammatory and anti-microbial properties [43][44][45][46][47][48] . This is the first study to our knowledge that explores the effects of aromoline on chondrocytes and chondrogenesis.…”

In Vitro and In Silico of Cholinesterases Inhibition and In Vitro and In Vivo Anti-Melanoma Activity Investigations of Extracts Obtained from Selected Berberis Species

“…The cytotoxicity was observed against all tested cell lines, with IC 50 values ranging from 245 to 473 μg/mL. Bersavine, a bisbenzylisoquinoline alkaloid isolated from Berberis vulgaris, inhibits the proliferation and viability of leukemic (Jurkat, MOLT-4), colon (HT-29), cervix (HeLa), and breast (MCF-7) cancer cells, with IC 50 values ranging from 8.1 to 11 μM [ 12 ]. A relatively low cytotoxicity (compared to doxorubicin) was reported for Berberis integerrima leaves extract against breast cancer (MCF-7), epidermal (A431), and glioma (U87-MG) cell lines [ 13 ].…”