Farnesol inhibits tumor growth and enhances the anticancer effects of bortezomib in multiple myeloma xenograft mouse model through the modulation of STAT3 signaling pathway

Lee, Jong Hyun; Chulwon, Kim; Kim, Sung Hoon; Sethi, Gautam; Ahn, Kwang Seok

doi:10.1016/j.canlet.2015.02.024

Cited by 118 publications

(77 citation statements)

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“…S. polyanthum leaves extract has also exhibited cytotoxic effect on HB4C5 human hybridoma and mouse colon 26 adenocarcinoma cells; 29 and on 3T3-L1 cell lines proliferation. 30 Some anti-tumour compounds such as farnesol 31 and squalene 32 were also found in this study. Previously, S. polyanthum leaves extract were reported to exhibit some anti-tumour promoting activity, but against Raji cells.…”

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confidence: 76%

GC-MS Analysis of Phytochemical Compounds in Syzygium polyanthum Leaves Extracted using Ultrasound-Assisted Method

Rahim¹,

Ismail²,

Omar³

et al. 2017

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Context:Syzygium polyanthum has been traditionally formulated by the folklore for the treatment of diseases including diarrhea, rheumatism, diabetes mellitus, hypercholesterolemia, hypertension, gastritis and hyperuricemia. Normally, its phytochemicals are always extracted using solvent, maceration and steam distillation methods, but the use of ultrasound-assisted extraction (UAE) method is still not well documented. Aims: This study aims to extract the phytochemical compounds present in S. polyanthum leaves using UAE and to identify them by Gas Chromatography-Mass Spectrometry (GC-MS) analysis. Methodology: The leaves were consecutively soaked with n-hexane, ethyl acetate and methanol in a bath sonicator to derive n-hexane (HSP), ethyl acetate (EASP), and methanol (MSP) extracts of S. polyanthum leaves and then the extracts were subjected to GC-MS analysis. Mass-spectral databases of peaks were compared with database from Wiley, NIST and FNSCC libraries for compound identification. Results: GC-MS analyses of HSP, EASP and MSP showed the presence of 21, 27, and 31 peaks, respectively. The major compound for HSP (31.912%), EASP (27.042%), and MSP (22.386%) were unknown compounds which were detected at retention time between 61.980 and 62.29 min, thus requires further characterization. Squalene and phytol were among the other major compounds present in all three extracts. Several identified compounds in the extracts such as squalene, phytol, hentriacontane, palmitic acid, α-pinene, nerolidol, linalool, α-tocopherol and β-tocopherol were known bioactive compounds. analysis of crude methanolic S. polyanthum leaves extract showed the presence of tannins, flavonoids, glycosides, alkaloids, carbohydrates, steroids, triterpenoids and flavonoids. 5,6 Phenolic compounds such as caffeic acid and gallic acid were previously identified in crude macerated methanolic extract of S. polyanthum leaves by high performance liquid chromatography and liquid chromatography mass spectrometry analyses. Conclusion: GC-MS analyses of n-hexane (HSP), ethyl acetate (EASP),7 Analysis on the crude macerated methanolic extract of S. polyanthum leaves has detected squalene as the major compound. 5,8 Another analysis on the macerated n-hexane extract similarly found squalene as the major compound (30.45%) followed by n-hentriacontane (6.57%). 8Most phytochemicals previously studied were extracted using solvent maceration and steam distillation methods, however, the use of ultrasound-assisted extraction (UAE) method is not well-documented. The present study has utilized UAE method, a different extraction method from the other previous studies. Basically, UAE method Rahim et al.: GC-MS Analysis of Syzygium polyanthum Leaves Extracted using Ultrasound-Assisted Extraction MethodPharmacognosy Journal, Vol 10, Issue 1, Jan-Feb, 2018 111 GC conditionThe injector temperature was set at 250 º C, column temperature program was set at 50ºC (0 min) with an increasing rate of 3 º C/min to 300 º C (10 min). The carrier gas used was pure helium gas (9...

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supporting

confidence: 76%

GC-MS Analysis of Phytochemical Compounds in Syzygium polyanthum Leaves Extracted using Ultrasound-Assisted Method

Rahim¹,

Ismail²,

Omar³

et al. 2017

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“…Signal transducer and activator of transcription 3 (STAT3) plays a critical role in proliferation, survival, apoptosis, angiogenesis, and metastasis [6,7] upon stimulation by several cytokines and growth factors during tumorigenesis [8,9]. STAT3 is a convergent point for a number of oncogenic signaling pathways via phosphorylation at tyrosine residue 705 [10].…”

Section: Introductionmentioning

confidence: 99%

Allicin Inhibits Proliferation and Invasion in Vitro and in Vivo via SHP-1-Mediated STAT3 Signaling in Cholangiocarcinoma

Chen

Zhu

Zhao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cholangiocarcinoma (CCA) is a malignant tumor that is resistant to chemotherapy, so new therapeutic agents are needed. Allicin which is rapidly converted from allin by allinase, is one of the most biologically active compounds in freshly crushed garlic and has been shown to have strong anti-tumor effects. Our aim was to explore the molecular mechanism by which allicin affects the cell proliferation and invasion of CCA. Methods: Cell viability and apoptosis were measured using the CCK-8 assay, colony formation assay, and flow cytometry. Cell migration and invasion were evaluated by wound healing and Transwell assays, respectively. The expression of several proteins involved in cell apoptosis and invasion were assessed by Western blot. The activation of STAT3 signaling was detected by Western blot and immunofluorescence staining. The involvement of SHP-1 was determined using small interfering RNA (siRNA). Moreover, a nude mouse model of human CCA was established to assess the anti-tumor effects of allicin in vivo. Results: Allicin significantly suppressed CCA cell proliferation by activating the caspase cascade, inducing apoptosis, and reducing the expression of proteins downstream of STAT3, such as B-cell lymphoma 2 (Bcl-2), while upregulating Bcl-2-associated X (Bax) protein. In addition, allicin inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of CCA cells. Moreover, the protein expression of MMP-2 and MMP-9 was significantly downregulated in CCA cells treated with allicin compared with CCA cells treated with control. Mechanistic investigations indicated that allicin upregulated SHP-1 expression in CCA, and pervanadate treatment reversed the allicin-induced downregulation of STAT3. Moreover, suppression of SHP-1 by siRNA overturned the effect of allicin on the induction of SHP-1 and inhibition of STAT3 activation. Additionally, treatment with allicin attenuated tumor growth in the nude mouse model of CCA. Conclusions: Our findings suggest that allicin suppresses cell proliferation and invasion via STAT3 signaling and may be a potential therapeutic agent for CCA.

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“…Reverse transcription polymerase chain reaction (RT-PCR) was performed as previously described [36]. …”

Section: Methodsmentioning

confidence: 99%

Capsazepine inhibits JAK/STAT3 signaling, tumor growth, and cell survival in prostate cancer

et al. 2016

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Persistent STAT3 activation is seen in many tumor cells and promotes malignant transformation. Here, we investigated whether capsazepine (Capz), a synthetic analogue of capsaicin, exerts anticancer effects by inhibiting STAT3 activation in prostate cancer cells. Capz inhibited both constitutive and induced STAT3 activation in human prostate carcinoma cells. Capz also inhibited activation of the upstream kinases JAK1/2 and c-Src. The phosphatase inhibitor pervanadate reversed Capz-induced STAT3 inhibition, indicating that the effect of Capz depends on a protein tyrosine phosphatase. Capz treatment increased PTPε protein and mRNA levels. Moreover, siRNA-mediated knockdown of PTPε reversed the Capz-induced induction of PTPε and inhibition of STAT3 activation, indicating that PTPε is crucial for Capz-dependent STAT3 dephosphorylation. Capz also decreased levels of the protein products of various oncogenes, which in turn inhibited proliferation and invasion and induced apoptosis. Finally, intraperitoneal Capz administration decreased tumor growth in a xenograft mouse prostate cancer model and reduced p-STAT3 and Ki-67 expression. These data suggest that Capz is a novel pharmacological inhibitor of STAT3 activation with several anticancer effects in prostate cancer cells.

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Farnesol inhibits tumor growth and enhances the anticancer effects of bortezomib in multiple myeloma xenograft mouse model through the modulation of STAT3 signaling pathway

Cited by 118 publications

References 46 publications

GC-MS Analysis of Phytochemical Compounds in Syzygium polyanthum Leaves Extracted using Ultrasound-Assisted Method

GC-MS Analysis of Phytochemical Compounds in Syzygium polyanthum Leaves Extracted using Ultrasound-Assisted Method

Allicin Inhibits Proliferation and Invasion in Vitro and in Vivo via SHP-1-Mediated STAT3 Signaling in Cholangiocarcinoma

Capsazepine inhibits JAK/STAT3 signaling, tumor growth, and cell survival in prostate cancer

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