Gallic Acid Induces the Apoptosis of Human Osteosarcoma Cells <i>In Vitro</i> and <i>In Vivo</i> via the Regulation of Mitogen-Activated Protein Kinase Pathways

Liang, Chengzhen; Zhang, Xin; Li, Hao; Tao, Yiqing; Tao, Lijiang; Yang, Zi-ru; Zhou, Xiaopeng; Shi, Zhijun; Tao, Huimin

doi:10.1089/cbr.2012.1245

Cited by 61 publications

(44 citation statements)

References 40 publications

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“…Cucurbitacin B exposure caused marked activation and enhanced expression of caspase-9, -8 and -3. These observations suggest that cucurbitacin B induces apoptosis via the intrinsic pathway, which is in accordance with a previous study using chemotherapeutic drugs as gallic acid (54). Furthermore, Liu et al (55) reported that the majority of chemotherapeutic drugs were able to induce apoptosis through the intrinsic mitochondrial pathway.…”

Section: Discussionsupporting

confidence: 91%

Cucurbitacin B inhibits cell proliferation and induces apoptosis in human osteosarcoma cells via modulation of the JAK2/STAT3 and MAPK pathways

Zhang

Gao

Yang

2017

Experimental and Therapeutic Medicine

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Abstract. Osteosarcoma (OS) is the most commonly diagnosed tumor of the bones in children and young adults. Even with conventional therapies the 5-year survival rate is ~65% in patients with OS. Considering the side effects and aggressiveness of malignant bone tumors, research is focussing on multi-targeted strategies in treatment. Cucurbitacin B, a triterpenoid compound has been demonstrated to induce apoptosis in various cancer cell types. The Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signalling cascades and mitogen activated protein kinases (MAPK) signalling cascades are critical regulators of tumorigenesis. The present study assessed the influence of cucurbitacin B on the viability and expression of MAPKs and proteins of the JAK2/STAT3 cascades in human OS cells (U-2 OS). Cucurbitacin B (20-100 µM) significantly reduced cell viability (P<0.05) and induced apoptosis, as assessed by MTT and Annexin V/propidium iodide staining, along with inhibiting cell migration. Gelatin zymography revealed supressed activities of matrix metalloproteinase (MMP-)2 and 9. Furthermore, cucurbitacin B effectively upregulated the apoptotic pathway and caused the effective inhibition of MAPK signalling and JAK2/STAT3 cascades. Multifold suppression of vascular endothelial growth factor by cucurbitacin B was also observed, indicating inhibition of angiogenesis. Thus, by downregulating major pathways-MAPK and JAK2/STAT3 and MMPs, cucurbitacin B has potent anti-proliferative and anti-metastatic effects that require further investigation with regards to cancer treatment.

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Section: Discussionsupporting

confidence: 91%

Cucurbitacin B inhibits cell proliferation and induces apoptosis in human osteosarcoma cells via modulation of the JAK2/STAT3 and MAPK pathways

Zhang

Gao

Yang

2017

Experimental and Therapeutic Medicine

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“…Several studies have suggested that Akt, p38, JNK, and ERK1/2 cascades have critical roles in the induction of apoptosis [30,31]. Therefore, to elucidate the mechanisms underlying IUA-induced apoptosis, the levels of Akt, p-Akt, p38, p-p38, JNK, p-JNK, ERK1/2, and p-ERK1/2 were analyzed by Western blotting in osteosarcoma cells.…”

Section: Discussionmentioning

confidence: 99%

A New Synthetic Ursolic Acid Derivative IUA with Anti-Tumor Efficacy Against Osteosarcoma Cells via Inhibition of JNK Signaling Pathway

Chen

Wang

et al. 2014

Cell Physiol Biochem

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Background: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and is characterized by frequent metastasis and resistance to chemotherapy. Because osteosarcoma cells are not highly susceptible to current chemotherapy drugs, new alternative strategies for the treatment of osteosarcoma are needed. This study was undertaken to investigate the inhibitory effects of a new synthetic ursolic acid derivative IUA on osteosarcoma cells and to explore its molecular mechanism. We also intended to identify new therapeutic candidates. Methods: We used MTT assay to assess the effect of IUA on the proliferation of osteosarcoma cells. Western-blot analysis was performed to examine downstream molecular events. The Annexin V method was used to evaluate the effect of IUA on apoptosis of osteosarcoma cells. The cell cycle of IUA-treated cells was examined by flow cytometry, and the in vivo effects of this new ursolic acid derivative were evaluated in a mouse osteosarcoma model. Results: The results showed that the new synthetic ursolic acid derivative IUA significantly decreased viability of osteosarcoma cells in vitro and in vivo. It could also induce apoptosis and G1 phase arrest of osteosarcoma cells. The JNK signaling pathway was significantly inhibited, and cleaved caspase-3 protein was increased. Conclusion: We concluded that the new synthetic ursolic acid derivative IUA induces proliferation inhibition and apoptosis of osteosarcoma cells in vitro and in vivo via the down-regulation of the JNK signaling pathway, making it a promising agent for the prevention and treatment of human osteosarcoma.

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“…In a similar fashion, ferulic acid at a dose of 10, 30 and 50 mg/kg body weight inhibited the melanoma tumor development in nude mice [88]. The trihydroxy benzoic acid (gallic acid at 0.3 and 1.0%) also inhibited the growth of osteocarcinomas in xenograft mice models [89]. The data showed a significant reduction in the tumor volume from 2392.99 mm 3 in control group to 1896.34 mm 3 and 1476.55 mm 3 in the treated groups [89].…”

Section: In Vivo Studiesmentioning

confidence: 99%

“…The trihydroxy benzoic acid (gallic acid at 0.3 and 1.0%) also inhibited the growth of osteocarcinomas in xenograft mice models [89]. The data showed a significant reduction in the tumor volume from 2392.99 mm 3 in control group to 1896.34 mm 3 and 1476.55 mm 3 in the treated groups [89]. Another study also demonstrated the anti-tumor potential of gallic acid.…”

Section: In Vivo Studiesmentioning

confidence: 99%

An overview on the role of dietary phenolics for the treatment of cancers

Anantharaju

Prathima

Vimalambike

et al. 2016

Nutr J

410

248

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Plant derived phenolic compounds have been shown to inhibit the initiation and progression of cancers by modulating genes regulating key processes such as: (a) oncogenic transformation of normal cells; (b) growth and development of tumors; and (c) angiogenesis and metastasis. Recent studies focusing on identifying the molecular basis of plant phenolics-induced cancer cell death have demonstrated down-regulation of: (a) oncogenic survival kinases such as PI3K and Akt; (b) cell proliferation regulators that include Erk1/2, D-type Cyclins, and Cyclin Dependent Kinases (CDKs); (c) transcription factors such as NF-kβ, NRF2 and STATs; (d) histone deacetylases HDAC1 and HDAC2; and (e) angiogenic factors VEGF, FGFR1 and MIC-1. Furthermore, while inhibiting oncogenic proteins, the phenolic compounds elevate the expression of tumor suppressor proteins p53, PTEN, p21, and p27. In addition, plant phenolic compounds and the herbal extracts rich in phenolic compounds modulate the levels of reactive oxygen species (ROS) in cells thereby regulate cell proliferation, survival and apoptosis. Furthermore, recent studies have demonstrated that phenolic compounds undergo transformation in gut microbiota thereby acquire additional properties that promote their biological activities. In vitro observations, preclinical and epidemiological studies have shown the involvement of plant phenolic acids in retarding the cancer growth. However, to date, there is no clinical trial as such testing the role of plant phenolic compounds for inhibiting tumor growth in humans. More over, several variations in response to phenolic acid rich diets-mediated treatment among individuals have also been reported, raising concerns about whether phenolic acids could be used for treating cancers. Therefore, we have made an attempt to (a) address the key structural features of phenolic acids required for exhibiting potent anti-cancer activity; (b) review the reported findings about the mechanisms of action of phenolic compounds and their transformation by gut microbiota; and (c) update the toxicological aspects and anti-tumor properties of phenolic compounds and extracts containing phenolic compounds in animals.

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Gallic Acid Induces the Apoptosis of Human Osteosarcoma Cells In Vitro and In Vivo via the Regulation of Mitogen-Activated Protein Kinase Pathways

Cited by 61 publications

References 40 publications

Cucurbitacin B inhibits cell proliferation and induces apoptosis in human osteosarcoma cells via modulation of the JAK2/STAT3 and MAPK pathways

Cucurbitacin B inhibits cell proliferation and induces apoptosis in human osteosarcoma cells via modulation of the JAK2/STAT3 and MAPK pathways

A New Synthetic Ursolic Acid Derivative IUA with Anti-Tumor Efficacy Against Osteosarcoma Cells via Inhibition of JNK Signaling Pathway

An overview on the role of dietary phenolics for the treatment of cancers

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