Baicalein induces apoptosis and autophagy of breast cancer cells via inhibiting PI3K/AKT pathway in vivo and vitro

Abstract

PurposeBaicalein, a widely used Chinese herbal medicine, has shown anticancer effects on many types of human cancer cell lines. However, little is known about the underlying mechanism in human breast cancer cells. In this study, we examined the apoptotic and autophagic pathways activated following baicalein treatment in human breast cancer cells in vitro and in vivo.Materials and methodsIn in vitro study, we used MTT and clone formation assay to confirm the inhibitory role of baicalein on proliferation of MCF-7 and MDA-MB-231 breast cancer cells. Apoptosis was detected employing Hoechst 33258 staining, JC-1 staining, and flow cytometry. Autophagy was monitored by acridine orange staining and transmission electron microscopy observation. Quantitative real-time PCR and Western blot analysis were employed to study the effects of baicalein on PI3K/AKT signaling components of MCF-7 and MDA-MB-231 breast cancer cells. In in vivo study, the effect of baicalein was tested with a breast cancer cells transplantation tumor model.ResultsOur study showed that baicalein has the potential to suppress cell proliferation, induce apoptosis and autophagy of breast cancer cells in vitro and in vivo. Furthermore, baicalein significantly downregulated the expression of p-AKT, p-mTOR, NF-κB, and p-IκB while enhancing the expression of IκB in MCF-7 and MDA-MB-231 cells. It also decreased the p-AKT/AKT and p-mTOR/mTOR ratios.ConclusionOur study demonstrated that baicalein induces apoptosis and autophagy of breast cancer cells via inhibiting the PI3K/AKT signaling pathway in vivo and vitro. Our study revealed that baicalein may be a potential therapeutic agent for breast cancer.

Drp1-mediated mitochondrial fission contributes to baicalein-induced apoptosis and autophagy in lung cancer via activation of AMPK signaling pathway

“…BA also increased the release of cytochrome c and Aif from mitochondria to cytoplasm. These results suggested that BA activated mitochondrial apoptotic pathway and induced apoptosis, which is consistent with other studies [18,20,21,34]. Moreover, BA increased mitochondrial fragmentation, promoted mitochondrial fission related protein expressions, and impaired mitochondrial functions such as cellular ATP depletion, decrease of mitochondrial mass and decrease of mitochondrial respiratory chain related protein expressions.…”

“…Previous studies have found that BA induces apoptosis and autophagy in multiple cancer cells [18,20,21,26], but the underlying mechanisms are still unclear. In the present study, we demonstrated that BA induced apoptosis and autophagy via activating Drp1-mediated mitochondrial fission in lung cancer A549 and H1299 cells.…”

“…Baicalein (BA) is a principle flavonoid component mainly isolated from the roots of Scutellaria baicalensis Georgi which is known as Huangqin in traditional Chinese medicine. The molecular structure of BA is shown in Fig 1a. Growing evidences demonstrate BA's role in treating and preventing multiple types of cancer, including breast cancer, bladder cancer, cervical cancer, hepatocellular cancer, lung cancer, ovarian cancer, osteosarcoma, and gallbladder cancer [18][19][20][21][22][23][24][25]. Inducing apoptosis [18,20,21], initiating autophagy [18], inhibiting tumor invasion and metastasis [19] and causing cell cycle arrest [26] may underlie the anticancer property of BA.…”

<p>Induction of Autophagy by Baicalin Through the AMPK-mTOR Pathway Protects Human Skin Fibroblasts from Ultraviolet B Radiation-Induced Apoptosis</p>

“…34 It is also effective in inhibiting UVB-induced photodamage in keratinocytes by harvesting reactive oxygen species, 20 reducing the increased apoptosis rate and suppressing oxidative DNA adducts, in which process the relevant cytokine secretion and the expression of several genes like p53 and p21 were reduced. 35 Meanwhile, baicalin has been shown to induce autophagy in a variety of cell types including hepatocellular carcinoma cells, 26,36 breast cancer cells, 37 and even mice brain. 38 In this context, we examined whether baicalin could protect fibroblast cells against UVB radiation via reducing apoptosis and inducing autophagy, and explored if the underlying mechanism of autophagy induction is via activation of AMPK and downregulation of mTOR.…”

PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer

“…The controls (untreated photoactivated and nonphotoactivated cells) displayed a physiological level of ca. 10% of apoptotic cells, corresponding with [61,62], but exhibited no necrosis ( Figure 6, SI Table S1). Similar results were detected for compound 1 at 0.1-1 µM concentration without photoactivation.…”