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

Abstract

Abstract. Scutellaria baicalensis (SB; Chinese name, huangqin) is widely used in Chinese medicine as a traditional adjuvant in the chemotherapy of lung and liver cancer. Baicalein is one of the bioactive flavonoid components isolated from the root of SB. The present study aimed to observe the effect of baicalein, in combination with platin-based systemic chemotherapy (cisplatin), on cytotoxicity and apoptosis of human A549 lung cancer cells. The cell cultures were treated with baicalein, cisplatin, or a combination of the two. Cell viability and cytotoxicity was assayed by XTT, and cell apoptosis was measured by flow cytometry. The apoptosis-associated proteins were detected by western blot analysis. The cytokines in the culture supernatant were detected by ELISA. The present study revealed that cisplatin and the baicalein-cisplatin combination inhibited viability and promoted cytotoxicity of A549 cells. Cisplatin, baicalein and baicalein-cisplatin combination treatments were effective in the promotion of apoptosis of A549 cells. Baicalein and baicalein-cisplatin combination treatments also inhibited B cell lymphoma-2 (Bcl-2) and increased Bcl-2-associated X protein (Bax) expression. Additionally, cisplatin, baicalein and the baicalein-cisplatin combination promoted caspase-3 expression. Furthermore, the baicalein-cisplatin combination suppressed the secretion of interleukin-6, and baicalein and the combination of baicalein cisplatin decreased the secretion of tumor necrosis factor-α of A549 cells. The present study concluded that baicalein combined with cisplatin induced cytotoxicity and apoptosis of A549 cells, and such activity may be associated with the regulation of Bcl-2, Bax and caspase-3, indicating a promising alternative method for lung cancer.

Inhibitory Effects of Scutellaria baicalensis Root Extract on Linoleic Acid Hydroperoxide-induced Lung Mitochondrial Lipid Peroxidation and Antioxidant Activities

“…SBR is a traditional Chinese medicine that is known as Huang-Qin, it was the first recorded in Shennong Bencaojing (The Classic of Herbal Medicine), and written between about 200 and 250 AD, for the treatment of bitter, cold, lung, and liver problems [35]. Recent studies have reported the anti-inflammatory properties activities to treat lung injury of SBR, the ability to blocked protein expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), phosphorylation of IκB-α protein and MAPKs in LPS-induce lung injury [36], the therapeutic effects of flavonoids-enriched extract from SBR on acute lung injury (ALI) induced by influenza A virus (IAV) in mice [37], reduced tumor progression and metastasis, directly induced tumor cell death, and inhibited tumor angiogenesis [38], attenuated the lung injury that was induced by myocardial ischemia and reperfusion, and, combined with cisplatin decreased the secretion of tumor necrosis factor-α of A549 cells, indicated a promising alternative method for lung cancer [39]. Accordingly, the present data (although far from conclusive) evidence a possible lung damage protection role of baicalein and the EtOAc extract of SBR.…”

Baicalein inhibits cell growth and increases cisplatin sensitivity of A549 and H460 cells via miR‐424‐3p and targeting PTEN/PI3K/Akt pathway

“…13,14 In addition, some studies have demonstrated the effects of baicalein on cisplatin sensitivity via different pathways in various cancer cells. [15][16][17] Baicalein has also exhibited a wide range of anti-inflammatory effects associated with airway injury, liver injury and rheumatoid arthritis. [18][19][20] In summary, baicalein has the potential to become an ideal adjuvant therapy in the treatment of cancer.…”

“…In addition to lung cancer, baicalein also inhibits the growth and metastasis of prostate cancer cells, the invasion of gastric cancer cells, the migration, adhesion and invasion of breast cancer cells, and induces apoptosis and autophagy in hepatocellular carcinoma cells . In addition, some studies have demonstrated the effects of baicalein on cisplatin sensitivity via different pathways in various cancer cells . Baicalein has also exhibited a wide range of anti‐inflammatory effects associated with airway injury, liver injury and rheumatoid arthritis .…”

Baicalein enhances the antitumor efficacy of docetaxel on nonsmall cell lung cancer in a β‐catenin‐dependent manner

“…As a bioactive flavone extracted from S. baicalensis Georgi, baicalein has been reported to inhibit the proliferation of various types of cancer cells and suppress tumor growth in vivo with limited toxicity to normal tissues, including NSCLC (Gong et al, ; Kiartivich et al, ; Yu et al, ), hepatocellular carcinoma (Bie et al, ; Zheng et al, ), breast cancer (Nguyen, Song, & Cho, ; Wang et al, ), and so on. Our previous studies have demonstrated that baicalein could inhibit nicotine‐induced proliferation and migration as well as augment the antitumor efficacy of cisplatin in A549 cells (Gong et al, ; Kiartivich et al, ). On the basis of our findings in vitro and the lack of studies concerning its combination with chemotherapy in vivo, we selected docetaxel, another commonly used chemotherapy agent in the treatment of NSCLC, and investigated whether the combination of baicalein and docetaxel would be more efficacious both in vitro and in vivo.…”

“…It contains a large number of flavonoids that possess antitumor activities, with baicalein being one of the major bioactive flavones (Gong, Zhao, Liu, Lu, & Dong, ). In recent years, an abundance of research has revealed that baicalein displays cytotoxicity to different kinds of NSCLC cells as well as antitumor efficacy in xenograft animal models with the capability to induce apoptosis, lead to cell‐cycle arrest, suppress angiogenesis, and inhibit metastasis (Gong et al, ; Kiartivich et al, ; Li‐Weber, ; Yu, Qi, Wu, Xu, & Liu, ). Furthermore, baicalein shows limited toxicity to normal tissues (Li‐Weber, ).…”