Pancracine, a montanine-type Amaryllidaceae alkaloid (AA), is one of the most potent compounds among natural isoquinolines. In previous studies, pancracine exhibited cytotoxic activity against diverse human cancer cell lines in vitro. However, further insight into the molecular mechanisms that underlie the cytotoxic effect of pancracine have not been reported and remain unknown. To fill this void, the cell proliferation and viability of cancer cells was explored using the Trypan Blue assay or by using the xCELLigence system. The impact on the cell cycle was determined by flow cytometry. Apoptosis was evaluated by Annexin V/PI and by quantifying the activity of caspases (-3/7, -8, and -9). Proteins triggering growth arrest or apoptosis were detected by Western blotting. Pancracine has strong antiproliferative activity on A549 cells, lasting up to 96 h, and antiproliferative and cytotoxic effects on MOLT-4 cells. The apoptosis-inducing activity of pancracine in MOLT-4 cells was evidenced by the significantly higher activity of caspases. This was transmitted through the upregulation of p53 phosphorylated on Ser392, p38 MAPK phosphorylated on Thr180/Tyr182, and upregulation of p27. The pancracine treatment negatively altered the proliferation of A549 cells as a consequence of an increase in G1-phase accumulation, associated with the downregulation of Rb phosphorylated on Ser807/811 and with the concomitant upregulation of p27 and downregulation of Akt phosphorylated on Thr308. This was the first study to glean a deeper mechanistic understanding of pancracine activity in vitro. Perturbation of the cell cycle and induction of apoptotic cell death were considered key mechanisms of pancracine action.

• MeSH
• Adenocarcinoma of Lung pathology   MeSH
• Alkaloids isolation & purification   pharmacology   MeSH
• Amaryllidaceae chemistry   MeSH
• Apoptosis drug effects   MeSH
• A549 Cells MeSH
• Hep G2 Cells MeSH
• Antineoplastic Agents, Phytogenic isolation & purification   pharmacology   MeSH
• Heterocyclic Compounds, 4 or More Rings isolation & purification   pharmacology   MeSH
• Leukemia pathology   MeSH
• Humans MeSH
• MCF-7 Cells MeSH
• Cell Line, Tumor MeSH
• Lung Neoplasms pathology   MeSH
• Cell Proliferation drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Bersavine is the new bisbenzylisoquinoline alkaloid isolated from the Berberis vulgaris L.(Berberidaceae) plant. The results of cytotoxicity screening 48 h post-treatment showed thatbersavine 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 bersavinetreatment in a time- and dose-dependent manner. Bersavine manifested concentration-dependentantiproliferative activity in human lung, breast, ovarian and hepatocellular carcinoma cell linesusing a xCELLigence assay. Significantly higher percentages of MOLT-4 cells exposed to bersavineat 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. Theupregulation of p53 phosphorylated on Ser392 was detected during the progression of MOLT-4 cellapoptosis. Mechanistically, bersavine-induced apoptosis is an effect of increased activity ofcaspases, while reduced proliferation seems dependent on increased Chk1 Ser345 phosphorylationand decreased Rb Ser807/811 phosphorylation in human leukemic cells.

• MeSH
• Alkaloids * chemistry   isolation & purification   pharmacology   MeSH
• Apoptosis drug effects   MeSH
• Berberis chemistry   MeSH
• Hep G2 Cells MeSH
• HT29 Cells MeSH
• Cytotoxins * chemistry   isolation & purification   pharmacology   MeSH
• Antineoplastic Agents, Phytogenic * chemistry   isolation & purification   pharmacology   MeSH
• G1 Phase drug effects   MeSH
• HeLa Cells MeSH
• Jurkat Cells MeSH
• Leukemia drug therapy   metabolism   pathology   MeSH
• Humans MeSH
• MCF-7 Cells MeSH
• Drug Screening Assays, Antitumor MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH