Vitexin induces apoptosis through mitochondrial pathway and PI3K/Akt/mTOR signaling in human non-small cell lung cancer A549 cells

Liu, Xiaoli; Jiang, Qingfeng; Liu, Huaimin; Luo, Suxia

doi:10.1186/s40659-019-0214-y

Cited by 87 publications

(52 citation statements)

References 19 publications

(17 reference statements)

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“…PI3K-AKT-mTOR is one of the major intracellular pathways, which serve a critical regulatory role among different kinds of tumor. mTOR is a key kinase of PI3K/ AKT downstream, it could regulate tumor cell proliferation, growth, survival and angiogenesis [42][43][44]. mTOR protein being proved to be regulated by two pathways.…”

Section: Discussionmentioning

confidence: 99%

PGC-1β cooperating with FOXA2 inhibits proliferation and migration of breast cancer cells

Cao¹,

Wang²,

Wang³

et al. 2019

Cancer Cell Int

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Background: Breast cancer is one of the most common malignancy among females from the worldwide cancer incidence statistics. Peroxisome gamma coactivator-1β (PGC-1β) has long been identified to be involved in this type of tumorigenesis. However, the mechanisms of PGC-1β in human breast cancer have not been fully understood and the function requires to be further elucidated. Methods: mRNA and protein expression of PGC-1β and FOXA2 in breast cancer tissues and cell lines were determined by qRT-PCR and Western Blotting, respectively. To further visualize the expression and localization of PGC-1β and FOXA2, immunochemistry and immunofluorescence staining methods were employed. The effect of PGC-1β and FOXA2 on cell proliferation and migration were evaluated by CCK8, clone formation, transwell and wound-healing assays, which has been done either with stable PGC-1β knockdown or FOXA2 overexpression in vitro. Xenografts model of nude mice were used to evaluate tumor growth in vivo. In addition, proteins expression of the PI3K-AKT-mTOR signaling pathway involved in the regulation of breast cancer were detected by Western Blotting. Results: Our results showed that PGC-1β was upregulated and FOXA2 was downregulated in breast cancer tissues and cell lines. These two proteins can be interacted with each other to form the complex. Also, we found the combination of PGC-1β interference with FOXA2 overexpression significantly inhibited cell proliferation and migration in vitro as well as tumor growth in vivo. We further identified that PGC-1β and FOXA2 strongly correlated with the PI3K-AKT-mTOR signaling pathway, and they exerted their biological functions by activating this pathway. Conclusions: We demonstrated that downregulation of PGC-1β combined with overexpression of FOXA2 obviously inhibited the function of breast cancer cells through regulating the PI3K-AKT-mTOR pathway.

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Section: Discussionmentioning

confidence: 99%

PGC-1β cooperating with FOXA2 inhibits proliferation and migration of breast cancer cells

Cao¹,

Wang²,

Wang³

et al. 2019

Cancer Cell Int

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“…More recently, vitexin has been shown to reduce the viability of adenocarcinomic human alveolar basal epithelial cells dose-dependently, with virtually no toxicity to normal human bronchial epithelial cells. Vitexin induced apoptosis in these cells by increasing pro-apoptotic protein expression, reducing mitochondrial membrane potential and through Akt signalling [398]. In a melanoma model, vitexin inhibited growth in vitro and in vivo, arrested the cell cycle in G2/M phase, induced apoptosis, caused DNA damage, and increased ROS accumulation.…”

Section: Vitexin and Isovitexinmentioning

confidence: 98%

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Tomko

Whynot

Ellis

et al. 2020

Cancers

149

139

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In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings. Cannabinoids have been suggested and shown to be effective in the treatment of various conditions. In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of cancer cells, as well as tumour angiogenesis. However, the therapeutic use of cannabinoids is currently limited to the treatment of symptoms and pain associated with chemotherapy, while their potential use as cytotoxic drugs in chemotherapy still requires validation in patients. Along with cannabinoids, cannabis contains several other compounds that have also been shown to exert anti-tumorigenic actions. The potential anti-cancer effects of cannabinoids, terpenes and flavonoids, present in cannabis, are explored in this literature review.

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“…These results collectively demonstrated that betulinic acid might be a potential and valuable mTOR inhibitor with hypo-toxicity in pancreatic cancer. As a valuable cancer therapy targets, mTOR signaling pathway has mainly modulated cancer cell autophagy or induced apoptosis [26,27]. The nutritional status, growth factor and other environmental stresses caused by mTORC1 complex can inhibit autophagy process to affect cancer cells [28].…”

Section: Discussionmentioning

confidence: 99%

“…The nutritional status, growth factor and other environmental stresses caused by mTORC1 complex can inhibit autophagy process to affect cancer cells [28]. Recently, the mTOR signaling pathway has also been reported to induce the apoptosis of non-small lung cancer [26], esophageal cancer [29] and myeloid leukemia cancer [30]. Nevertheless, the exact molecular mechanism of mTOR signaling regulated by betulinic acid in pancreatic cancer remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Chemopreventive effect of Betulinic acid via mTOR -Caspases/Bcl2/Bax apoptotic signaling in pancreatic cancer

Guo

Zhu

Wang

et al. 2020

BMC Complement Med Ther

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Background: Pancreatic cancer is aggressive with no symptoms until the advanced stage reached. The increased resistance of pancreatic cancer to chemotherapy demonstrates a dilemma in the clinical field. Hence, it is a matter of great urgency to develop an effective drug to treat patients with pancreatic cancer. Betulinic acid is a major triterpene isolated from spina date seed. Several studies have suggested its low toxicity and side effects to patients with malaria and inflammation. However, relevant studies on betulinic acid in inhibiting cancer were insufficient and the molecular mechanism was unclear. This study aimed to systematically explore the potential anti-cancer functions of betulinic acid in pancreatic cancer, and investigate its underlying molecular mechanism. Methods: The Counting Kit-8 assay, colony formation, transwell invasion assay, wound healing assay, flow cytometry and xenograft nude mice model were used to evaluate the effect of betulinic acid on the proliferation, invasion and migration ability of pancreatic cancer cells. Results: Our results showed that betulinic acid obviously suppressed pancreatic cancer both in vitro and in vivo in a dose-dependent manner. We also determined that betulinic acid inhibited pancreatic cancer by specifically targeting mTOR signaling rather than Nrf2 or JAK2. Conclusions: These findings clarify that betulinic acid is a potential and valuable anticancer agent for pancreatic cancer, and indicate the specific molecular target of betulinic acid.

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Vitexin induces apoptosis through mitochondrial pathway and PI3K/Akt/mTOR signaling in human non-small cell lung cancer A549 cells

Cited by 87 publications

References 19 publications

PGC-1β cooperating with FOXA2 inhibits proliferation and migration of breast cancer cells

PGC-1β cooperating with FOXA2 inhibits proliferation and migration of breast cancer cells

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Chemopreventive effect of Betulinic acid via mTOR -Caspases/Bcl2/Bax apoptotic signaling in pancreatic cancer

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