Extensive research has been carried out to study the effects useful site of berberine on cancer cells in vitro. This may be related to recent discovery of anti-cancer drugs with natural compound origin, for example, paclitaxel and topotecan.Various human cancer cell lines were used to demonstrate the anti-cancer effects of berberine in vitro. These include cancer cell lines of the tongue, stomach, lung, colon, liver, breast, prostate, nasopharyngeal, neurones, epidermal, and blood [18�C28]. Berberine has shown to induce cancer cell death via several mechanisms such as regulation of apoptosis proteins and cell cycle arrest.Berberine treatment increased the expression of apoptotic cell death proteins, promotes cell cycle arrest, and induces cell death in human cancer cell lines.

For instance, in human prostate epithelial cells (PWR-1E), berberine-increased expression of BCL2-associated X protein (Bax) was observed after berberine treatment, inducing cell death and demonstrating pro-apoptotic properties [29]. Similar effects of berberine were observed in prostate carcinoma cells (DU145, PC-3, and LNCaP) [21, 30]. Berberine also increased levels of Bax in promyelocytic leukemia cells [31], gastric carcinoma cells [24], and lung cancer cells [20].Berberine can also promote cell death by the regulation of antiapoptotic proteins. Decreased expression of antiapoptotic Bcl-2 protein was observed in human oral squamous cell carcinoma after berberine treatment [23]. Studies done in other cancer cell lines such as lung cancer, gastric cancer, and prostate cancer also showed reduced levels of Bcl-2 after berberine treatment [20, 21, 24, 30].

Cell cycle arrest at different phases has also been observed in human cancer cell lines after treatment with berberine. In giant cell carcinoma and prostate carcinoma cells, berberine also decreased G0/G1 phase-associated cyclins (D1, D2, E, Cdk2, Cdk4, and Cdk6), inducing G0/G1 arrest and suppressing cell proliferation [21, 25, 30, 32]. Further, in HepG2 cells, berberine acted on B-cell CLL/lymphoma 2 (BCL2), procaspase-3 and -9, and poly (ADP-ribose) polymerase (PARP), induced cell cycle arrest at G2/M phase and inhibited cell proliferation [22].Further, berberine can promote cell death via the regulation of pro- and antiapoptotic proteins. In addition to this, berberine can also promote apoptosis via mitochondrial/caspase pathway.

In cancer cell lines (tongue Drug_discovery cancer, oral squamous cell carcinoma and prostate epithelial) [18, 23, 29, 33], activation of caspases-3 & -9 promotes G1 cell cycle arrest in different human cancer cell lines (lung, stomach, and prostate) [20, 21, 24, 30, 33].Berberine also showed anti-metastatic properties in several cancer cell lines, acting on 72kDa type IV collagenase (MMP2), Cdc42 effector protein 1 (CDC42EP1), and ras-related C3 botulinum toxin substrate 1 (RAC1), transforming protein RhoA (RHOA) and urokinase-plasminogen activator A (PLAU) [34, 35].