Anti-proliferative effect of 8α-tigloyloxyhirsutinolide-13-O-acetate (8αTGH) isolated from Vernonia cinerea on oral squamous cell carcinoma through inhibition of STAT3 and STAT2 phosphorylation

Pouyfung, Phisit; Choonate, Sirinthip; Wongnoppavich, Ariyaphong; Rongnoparut, Pornpimol; Chairatvit, Kongthawat

doi:10.1016/j.phymed.2018.09.211

Cited by 20 publications

(12 citation statements)

References 27 publications

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“…In addition, our results showed that V. polyanthes aqueous extract present no genotoxic effect on A. cepa root. As discussed before, the presence of flavonoids and terpenoids could account for the lack of mutagenic effects caused by infusions of these extract (Teixeira et al, 2003;Perveen, 2018). Similarly to what was observed in this work, Costus spiralis (Sousa et al, 2017), Sambucus australis (Tedesco et al, 2017), Luchea divaricata (Frescura et al, 2012) and Solidago microglossa (Bagatini et al, 2009) medicinal extracts also presented cytotoxic but no genotoxic or mutagenic effect using A. cepa test.…”

Section: Discussionsupporting

confidence: 84%

“…For human helthcare, the terpenoids exhibit important pharmacological activities, such as antimicrobial, antiviral, anti-fungal, anti-inflammatory, antihyperglycemic and antiparasitic activities, as well as are effective in chemoprevention and chemotherapy (Paduch et al, 2007). There are some terpenoids such as paclitaxel and its derivate which are commonly used as anticancer drugs (Perveen, 2018). However, complementary studies are necessary to determine the correlation of the flavonoids and terpenoids with the antiproliferative cell activity.…”

Section: Discussionmentioning

confidence: 99%

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Cytotoxic effect of Vernonanthura polyanthes leaves aqueous extracts

et al. 2021

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Vernonanthura polyanthes, popularly known as assa-peixe, is a medicinal plant that has been widely used by Brazilian Cerrado population for treatment of diseases without a detailed evaluation of their effectiveness, toxicity, and proper dosage. Thus, more studies investigating the safety of V. polyanthes aqueous extract before the use are needed. The purpose of this study was to evaluate the toxicity, cytotoxicity and genotoxicity of V. polyanthes leaves aqueous extract using the Artemia salina and Allium cepa assays. For the A. salina assay, three groups of 10 larvae were exposed to V. polyanthes leaves aqueous extract at the concentrations of 5, 10, 20, 40, and 80 mg/ml. For the A. cepa assay, 5 onion bulbs were exposed to V. polyanthes leaves aqueous extract at 10, 20, and 40 mg/ml, and then submitted to macroscopic and microscopic analysis. As result it was identified a toxicity and cytotoxicity of V. polyanthes dependent on the extract concentration. The A. salina assay suggests that the concentration of 24 mg/ml of the V. polyanthes extract is able to kill 50% of naupllis; while the A. cepa assay suggests that V. polyanthes leaves aqueous extract is toxic at concentrations higher than 20 mg/ml; however the cytotoxic effect in A. cepa root cells was observed at 40 mg/ml of the extract. It is important to say that the V. polyanthes leaves aqueous extract concentration commonly used in popular medicine is 20 mg/ml. Thus, the popular concentration used is very close to toxicity limit in A. salina model (24 mg/ml) and is the concentration which showed toxic effect in A. cepa root cells (20 mg/ml). No genotoxic activity of V. polyantes leaves aqueous extract was observed in the conditions used in this study. Because of the antiproliferative action and no genotoxic activity, V. polyanthes leaves aqueous extract may present compounds with potential use for human medicine. However more detailed studies need to be performed to confirm this potential.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Cytotoxic effect of Vernonanthura polyanthes leaves aqueous extracts

et al. 2021

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“…278 Pouyfung et al showed that 8α-tigloyloxyhirsutinolide-13-O-acetate (8αTGH), a compound from Vernonia cinerea, has anti-tumor activity in an HNSCC mouse model through inhibiting the JAK/STAT3 pathway. 220 JAK inhibitors were mainly designed for autoimmune dysfunction treatment. Although some of them demonstrated anti-tumor utility, the results of clinical trials for cancer treatment were still modest.…”

Section: Targeting Upstream Receptorsmentioning

confidence: 99%

STAT3 pathway in cancers: Past, present, and future

Wang

Man

Huo

et al. 2022

MedComm

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Signal transducer and activator of transcription 3 (STAT3), a member of the STAT family, discovered in the cytoplasm of almost all types of mammalian cells, plays a significant role in biological functions. The duration of STAT3 activation in normal tissues is a transient event and is strictly regulated. However, in cancer tissues, STAT3 is activated in an aberrant manner and is induced by certain cytokines. The continuous activation of STAT3 regulates the expression of downstream proteins associated with the formation, progression, and metastasis of cancers. Thus, elucidating the mechanisms of STAT3 regulation and designing inhibitors targeting the STAT3 pathway are considered promising strategies for cancer treatment. This review aims to introduce the history, research advances, and prospects concerning the STAT3 pathway in cancer. We review the mechanisms of STAT3 pathway regulation and the consequent cancer hallmarks associated with tumor biology that are induced by the STAT3 pathway. Moreover, we summarize the emerging development of inhibitors that target the STAT3 pathway and novel drug delivery systems for delivering these inhibitors. The barriers against targeting the STAT3 pathway, the focus of future research on promising targets in the STAT3 pathway, and our perspective on the overall utility of STAT3 pathway inhibitors in cancer treatment are also discussed.

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“…36 Therefore, targeting the JAK/STAT signaling may be a potential therapeutic strategy against human cancer including oral cancer. 18,37 Based on the important role of JAK/STAT signaling in oral cancer, many anticancer agents targeting JAK/STAT in oral cancer have been identified, and some of which are well studied under experimental conditions such as honokiol, 37 astaxanthin, 18 8αTGH, 38 Blueberry and malvidin. 39 Here, we demonstrated that flavopereirine obviously decreased the expression levels of p-JAK2, p-STAT3 and p-STAT5.…”

Section: Discussionmentioning

confidence: 99%

Flavopereirine Suppresses the Progression of Human Oral Cancer by Inhibiting the JAK-STAT Signaling Pathway via Targeting LASP1

Xu¹,

Wu²,

Huang³

2021

DDDT

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Objective: Flavopereirine has been identified to be a potential anti-cancer agent in several types of human cancer. This study aimed to investigate the anti-cancer activity of flavopereirine in oral cancer. Methods: The effect of flavopereirine on cell viability of human oral cancer cell lines (BcaCD885 and Tca8113) was evaluated by MTT assay and colony formation assay. Cell apoptosis and cell cycle distribution were detected by flow cytometry. Cell invasion and migration were evaluated by Transwell assay. The expression of LASP1, JAK2, p-JAK2, STST3, p-STST3, STST5 and p-STST5 was evaluated by qRT-PCR and Western blot. In addition, the xenograft mouse model was constructed to determine the anti-cancer role of flavopereirine in vivo. Results: Flavopereirine significantly inhibited cell proliferation, invasion, migration and EMT process of BcaCD885 and Tca8113 cells, while promoted cell apoptosis in vitro. Flavopereirine markedly decreased the expression levels of p-JAK2, p-STST3 and p-STST5, while increased the expression levels of LASP1. In addition, downregulation of LASP1 significantly increased the expression levels of p-JAK2, p-STAT3 and p-STAT5 compared with si-NC in BcaCD885 cells. Moreover, flavopereirine was found to decrease tumor weight and volume of xenograft tumors in vivo. Conclusion:Flavopereirine inhibited the progression of oral cancer through inactivating the JAK/STAT signaling pathway by upregulating LASP1, suggesting that flavopereirine might be a potential anti-cancer agent for oral cancer.

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Anti-proliferative effect of 8α-tigloyloxyhirsutinolide-13-O-acetate (8αTGH) isolated from Vernonia cinerea on oral squamous cell carcinoma through inhibition of STAT3 and STAT2 phosphorylation

Cited by 20 publications

References 27 publications

Cytotoxic effect of Vernonanthura polyanthes leaves aqueous extracts

Cytotoxic effect of Vernonanthura polyanthes leaves aqueous extracts

STAT3 pathway in cancers: Past, present, and future

Flavopereirine Suppresses the Progression of Human Oral Cancer by Inhibiting the JAK-STAT Signaling Pathway via Targeting LASP1

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