Baicalein, a component of Scutellaria baicalensis, induces apoptosis by Mcl-1 down-regulation in human pancreatic cancer cells

Abstract

Scutellaria baicalensis (SB) and SB-derived polyphenols possess anti-proliferative activities in several cancers, including pancreatic cancer (PaCa). However, the precise molecular mechanisms have not been fully defined. SB extract and SB-derived polyphenols (wogonin, baicalin, and baicalein) were used to determine their anti-proliferative mechanisms. Baicalein significantly inhibited the proliferation of PaCa cell lines in a dose-dependent manner, whereas wogonin and baicalin exhibited a much less robust effect. Treatment with baicalein induced apoptosis with release of cytochrome c from mitochondria, and activation of caspase-3 and -7 and PARP. The general caspase inhibitor zVAD-fmk reversed baicalein-induced apoptosis, indicating a caspase-dependent mechanism. Baicalein decreased expression of Mcl-1, an anti-apoptotic member of the Bcl-2 protein family, presumably through a transcriptional mechanism. Genetic knockdown of Mcl-1 resulted in marked induction of apoptosis. The effect of baicalein on apoptosis was significantly attenuated by Mcl-1 over-expression, suggesting a critical role of Mcl-1 in this process. Our results provide evidence that baicalein induces apoptosis in pancreatic cancer cells through down-regulation of the anti-apoptotic Mcl-1 protein.

Regulation of cytotoxicity and apoptosis-associated pathways contributes to the enhancement of efficacy of cisplatin by baicalein adjuvant in human A549 lung cancer cells

“…However, there are numerous side effects associated with this type of treatment (5). Baicalein has been proposed in several extensive studies as a potential candidate for the treatment of cancer (14,15,18). In the present study, the effect of cisplatin combined with baicalein (a flavonoid component isolated from the root of traditional Chinese medicine SB) on cytotoxicity and apoptosis of human lung cancer cells A549 was examined.…”

“…Baicalein, an important bioactive flavonoid purified from SB, is one of the most prominent and multi-therapeutic traditional Chinese medicines used in ancient China for the therapeutics of numerous diseases. Baicalein can increase the chemosensitivity of anti-cancer drugs by regulating cell proliferation, apoptosis and the cell cycle, as well as by preventing and attenuating the side effects of chemotherapeutic agents and radiation through the modulation of various targets (18). Over the past decade, numerous studies have demonstrated the potent anti-cancer effects of baicalein in various types of lung malignancies (19,20).…”

Virtual Screening of Phytochemicals to Novel Target (HAT) Rtt109 in Pneumocystis Jirovecii using Bioinformatics Tools

“…A low clog p-value indicates that the compound has high hydrophylicity and better absorption. The compound also has a high drug likeness score indicating that it is a potential drug candidate [28].…”

Modulation of Colitis-associated Colon Tumorigenesis by Baicalein and Betaine

“…21 Baicalein exhibits various biological effects, including anti-inflammatory 22 and anti-tumor activity. 23 So far, Scutellaria has been shown to have almost no or very low toxicity to animals and humans. 24 It is also evident that this flavonoid exhibits selective cytotoxicity against malignant cells.…”