Induction of G1 Arrest and Apoptosis in Human Cancer Cells by Crebanine, an Alkaloid from <i>Stephania venosa</i>

Abstract

In this study, we focused the effects of crebanine, an alkaloid isolated from the tuber of Stephania venosa, on various human cancer cells. Crebanine treatment was found to significantly inhibit the proliferation of human leukemic cells (HL-60, U937 and K562), human fibrosarcoma cells (HT1080) and cervix cancer cell lines (KB-3-1 and KB-V1), of which HL-60 cells were the most sensitive to its treatment. In contrast, crebanine caused much less toxicity in human normal fibroblast cells. Our results demonstrated that crebanine mediated cell cycle arrest at G0/G1 phase and this was associated with down-regulation of cyclins A and D. In addition, crebanine induced apoptosis, which was detected by observation of the membrane phospholipid exposure in flow cytometry. Its induction of apoptosis was accompanied by an increase in cleavage of caspase-3, -8, -9 and poly(ADP-ribose) polymerase (PARP), and was attributable to the augmentation of Bax/Bcl proteins level. Crebanine also decreased mitochondrial membrane potential. Taken together, crebanine exerts anti-proliferative effects on human cancer cells through the induction of cell cycle arrest at the G1 phases and apoptosis. Our results suggest that crebanine is a promising new candidate as a chemotherapeutic agent for cancer therapy.

Antiinflammatory Activities of Crebanine by Inhibition of NF-κB and AP-1 Activation through Suppressing MAPKs and Akt Signaling in LPS-Induced RAW264.7 Macrophages

“…Crebanine exhibits a variety of biological properties including, anti-microbial activities, improvement of neurodegenerative diseases, as well as antiinvasion and anti-proliferation activities in cancer cells. [14][15][16] Moreover, our previous report demonstrated that crebanine reduced TNF-α induced lung cancer cells proliferation and invasion via suppressing NF-κB activity.…”

Roles of Plant Extracts and Constituents in Cervical Cancer Therapy

“…Additionally, it was also shown in the same study that presence of a free phenolic function at C-6 or C-7 show significantly high cytotoxicity toward the KB cancer cell line as in the case of some of the alkaloids. In this same cell line, another alkaloid-crebanine, isolated from the tuber of Stephania venosa, has also been investigated for its anticancer properties in vitro (Wongsirisin et al, 2012). Here, cells treated with 70.7 μM of crebanine for 48 h demonstrated inhibition in cell growth, with the IC 50 of 24 μg/mL.…”

Stephanine from Stephania venosa (Blume) Spreng Showed Effective Antiplasmodial and Anticancer Activities, the Latter by Inducing Apoptosis through the Reverse of Mitotic Exit

“…The phytochemical studies on this genus have indicated the isoquinoline alkaloids as the main chemical constituents with over 200 of which have been described (Semwal et al, 2010). Many of these constituents have important pharmacological activities including anti-proliferative (Bun et al, 2009;Nantapap et al, 2010;Wongsirisin et al, 2012), antimalarial (Likhitwitayawuid et al, 1993), antimicrobial (Deng et al, 2011), acetylcholinesterase-inhibiting (Tran et al, 2010), antihyperglycemic (Tsutsumi et al, 2003) and antiprotozoal activities (Camacho et al, 2000). The extracts of the tubes of S. venosa and their aporphine alkaloids isolated (e.g.…”