Fangchinoline Inhibits Cell Proliferation Via Akt/GSK-3beta/cyclin D1 Signaling and Induces Apoptosis in MDA-MB-231 Breast Cancer Cells

Wang, Chang‐Dong; Yuan, Chengfu; Bu, Youquan; Wu, Xiangbing; Wan, Jinyuan; Zhang, Li; Hu, Ning; Liu, Xianjun; Zu, Yong; Liu, Geli; Song, Fangzhou

doi:10.7314/apjcp.2014.15.2.769

Cited by 42 publications

(37 citation statements)

References 14 publications

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“…Fangchinoline also induced autophagic cell death via p53/sestrin2/AMPK signaling in human hepatocellular carcinoma cells (24). Reports also indicated that fangchinoline inhibited cell proliferation via Akt/GSK-3β/cyclin D1 signaling and induce apoptosis in MDA-MB-231 breast cancer cells (10,11,25). Researchers pointed out that fangchinoline could achieve the inhibition of lung cancer and glioma role by regulating multiple signaling pathways (26,27).…”

Section: Discussionmentioning

confidence: 99%

Fangchinoline suppresses growth and metastasis of melanoma cells by inhibiting the phosphorylation of FAK

et al. 2017

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Melanoma is a malignant tumor with high degree of malignancy, metastasis and high mortality. The etiology of melanoma has not been fully elucidated, and there is no effective drug for the complete treatment of melanoma. In recent years, many traditional Chinese herbal medicines have played an important role in clinical treatment and experimental research on cancer. As a natural product, fangchinoline has the characteristics of enhancing immune function, low toxicity and good liver protection features, so it is considered to be a new type of anticancer drug. In the present study, we found that fangchinoline has inhibitory effects on the proliferation and metastasis of A375 and A875 cells in a concentration-dependent manner. Fangchinoline inhibited the proliferation of A375 and A875 cell activity with IC50 values of 12.41 and 16.20 µM. We also found that fangchinoline could significantly reduce the phosphorylation of Focal adhesion kinase (FAK). In summary, we demonstrated that fangchinoline inhibits the proliferation and metastasis of melanoma cells by suppressing FAK and its downstream signaling pathway. More importantly, we provide a novel mechanism that fangchinoline could be an effective candidate for the treatment of melanoma.

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Section: Discussionmentioning

confidence: 99%

Fangchinoline suppresses growth and metastasis of melanoma cells by inhibiting the phosphorylation of FAK

et al. 2017

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“…antagonizes multidrug resistance-related drugs by targeting P-glycoprotein, which may improve drug resistance in chemotherapy [21]. Fcn targets the PI3K/Akt/GSK-3β pathway and induces apoptosis [13]. Fcn can also modulate cell cycle-related proteins, such as PCNA, p27 and cyclin D, and thus induces G1/S arrest in prostate cancer [20].…”

Section: Fangchinoline Induces Energetic Impairment In Bladder Cancermentioning

confidence: 99%

“…Fcn is a potent antioxidant, showing protective effects in oxidative cell injury [10]. This compound was also found to inhibit the growth of several cancers, such as lung cancer, breast cancer and prostate cancer, through proliferation inhibition and/or apoptosis [11][12][13][14] and induces autophagic cell death in hepatocellular cancer cells [15]. More recently, Fcn was found to block the well-known P-glycoprotein, indicating that Fcn may enhance the effects of chemotherapy drugs and prevents multidrug resistance [16].…”

Section: Introductionmentioning

confidence: 99%

Fangchinoline Induces Apoptosis, Autophagy and Energetic Impairment in Bladder Cancer

Fan¹,

Zhang²,

Ma³

et al. 2017

Cell Physiol Biochem

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Key Words Bladder cancer • Fangchinoline • Autophagy • Apoptosis • ProliferationAbatract Background/Aims: Tetrandrine and Fangchinoline (Fcn) are two natural products that are found in Stephania tetrandra. Tetrandrine is a known anti-bladder cancer compound, but the effects of Fcn on bladder cancer have been previously unclear. In the present study, we focused on the anti-tumor effects of Fcn on bladder cancer. Methods and Results: We treated T24 and 5637 bladder cancer cell lines with Fcn in vitro. We observed that Fcn inhibited the viability of bladder cancer cells in a concentration-dependent manner. The expression of PCNA, a biomarker of proliferation, was down-regulated. Fcn treatment induced both apoptosis and autophagy in bladder cancer cells, as shown by the increased cleavage of caspase-3, an upregulated LC3-II/LC3-I ratio and the down-regulated p62 level. Blocking autophagy with 3-MA (3-Methyladenine) enhanced Fcn-induced apoptosis, indicating that Fcn-induced autophagy was adaptive. Additionally, we observed that Fcn treatment inhibited mTOR and reduced the intracellular ATP levels. The exogenous addition of methyl pyruvate (MP) to compensate metabolic substrates alleviated Fcn-induced apoptosis and autophagy. Conclusions: Our data indicated that Fcn caused an impairment in energy generation, which led to apoptosis and adaptive autophagy in bladder cancer. These results demonstrated that Fcn may be a potential candidate for use in the prevention and treatment of bladder cancer.

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“…Additionally, most studies have revealed the therapeutic potential of fangchinoline, an alkaloid derived from the dry roots of Stephania tetrandra S Moore (Menispermaceae). It can inhibit the proliferation of MCF-7 and MDA-MB-231 human breast cancer cells and PC3 human prostate carcinoma cells via G1-phase arrest [125, 126] and induce apoptosis in breast cancer cells via the mitochondrial apoptotic pathway and Akt/GSK-3beta/cyclin D1 signaling [127, 128]. Fangchinoline effectively suppressed the proliferation and invasion of lung cancer A549 cells by inhibiting p-FAK and its downstream pathways [129] and induced autophagic cell death via p53/sestrin2/AMPK signaling in hepatocellular carcinoma HepG2 and PLC/PRF/5 cells [130].…”

Section: Effects Of Tetrandrine Analogs and Other Bisbenzylisoquinolimentioning

confidence: 99%

Tetrandrine, a Chinese plant-derived alkaloid, is a potential candidate for cancer chemotherapy

Liu

2016

Oncotarget

143

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Cancer is a disease caused by the abnormal proliferation and differentiation of cells governed by tumorigenic factors. Chemotherapy is one of the major cancer treatment strategies, and it functions by targeting the physiological capabilities of cancer cells, including sustained proliferation and angiogenesis, the evasion of programmed cell death, tissue invasion and metastasis. Remarkably, natural products have garnered increased attention in the chemotherapy drug discovery field because they are biologically friendly and have high therapeutic effects. Tetrandrine, isolated from the root of Stephania tetrandra S Moore, is a traditional Chinese clinical agent for silicosis, autoimmune disorders, inflammatory pulmonary diseases, cardiovascular diseases and hypertension. Recently, the novel anti-tumor effects of tetrandrine have been widely investigated. More impressive is that tetrandrine affects multiple biological activities of cancer cells, including the inhibition of proliferation, angiogenesis, migration, and invasion; the induction of apoptosis and autophagy; the reversal of multidrug resistance (MDR); and the enhancement of radiation sensitization. This review focuses on introducing the latest information about the anti-tumor effects of tetrandrine on various cancers and its underlying mechanism. Moreover, we discuss the nanoparticle delivery system being developed for tetrandrine and the anti-tumor effects of other bisbenzylisoquinoline alkaloid derivatives on cancer cells. All current evidence demonstrates that tetrandrine is a promising candidate as a cancer chemotherapeutic.

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Fangchinoline Inhibits Cell Proliferation Via Akt/GSK-3beta/cyclin D1 Signaling and Induces Apoptosis in MDA-MB-231 Breast Cancer Cells

Cited by 42 publications

References 14 publications

Fangchinoline suppresses growth and metastasis of melanoma cells by inhibiting the phosphorylation of FAK

Fangchinoline suppresses growth and metastasis of melanoma cells by inhibiting the phosphorylation of FAK

Fangchinoline Induces Apoptosis, Autophagy and Energetic Impairment in Bladder Cancer

Tetrandrine, a Chinese plant-derived alkaloid, is a potential candidate for cancer chemotherapy

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