Tetramethylpyrazine (TMPZ) triggers S-phase arrest and mitochondria- dependent apoptosis in lung cancer cells

Huang, Haiyan; Liu, F B; Ruan, Zhengyi; Zheng, Jiawei; Su, Yun-Ai; Wang, J

doi:10.4149/neo_2018_170112n26

Cited by 16 publications

(18 citation statements)

References 28 publications

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“…It indicated that the inhibitory effect of ligustrazine on cell proliferation was a positive correlation to the concentration and treatment time. The findings demonstrated that ligustrazine had significant anti-tumor activity, which was consistent with previous studies (21)(22)(23).…”

Section: Discussionsupporting

confidence: 92%

Ligustrazine induces the colorectal cancer cells apoptosis via p53-dependent mitochondrial pathway and cell cycle arrest at the G0/G1 phase

Bian¹,

Yang²,

Sheng³

et al. 2021

Ann Palliat Med

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Background: Ligustrazine, active ingredients extracted from the natural herb Ligusticum Chuanxiong Hort, has promising anti-tumor properties on tumor cell lines. However, the potential anti-tumor activity of ligustrazine on colorectal cancer (CRC) cells and the molecular mechanisms have not been elucidated. In this study, we explored the critical functions of ligustrazine on SW480 and CT26 cells at cellular levels.Methods: CCK-8 assay was performed to analyze the cell viability. Flow cytometry analysis was applied to study cell apoptosis and cell cycle. The expressions of cell apoptosis and cell cycle-associated proteins were conducted by western blot and qRT-PCR analysis.Results: Ligustrazine showed significant inhibitory effects on the proliferation of SW480 and CT26 cells.Ligustrazine induced cell apoptosis was associated with the up-regulation of pro-apoptotic protein and the down-regulation of anti-apoptotic protein in an activated mitochondrial-dependent pathway. And it indicated that ligustrazine induced cell cycle arrest by changing the cell cycle distribution, which leads to cell cycle arrest at the G0/G1 phase. Besides, the ligustrazine-induced cell apoptosis and cell cycle arrest were markedly reversed by pifithrin-α (p53 inhibitor), which suggested that ligustrazine-induced cell apoptosis was achieved by regulating p53-dependent mitochondrial pathway and cell cycle arrest at the G0/G1 phase.Conclusions: These findings demonstrated that ligustrazine could induce SW480 and CT26 cells apoptosis via a p53-dependent mitochondrial pathway and cell cycle arrest at the G0/G1 phase. Ligustrazine may serve as a potential anti-cancer agent for CRC.

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Section: Discussionsupporting

confidence: 92%

Ligustrazine induces the colorectal cancer cells apoptosis via p53-dependent mitochondrial pathway and cell cycle arrest at the G0/G1 phase

Bian¹,

Yang²,

Sheng³

et al. 2021

Ann Palliat Med

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“…TMP has shown antitumor effects on various tumor types ( Figure 2 ), including brain glioma ( Cai et al, 2014 ), breast ( Fan et al, 2021 ), prostate ( Zhou et al, 2020 ), and lung cancers ( Huang et al, 2018 ). Tumor growth can be reversed by applying different concentrations of TMP to tumor cells.…”

Section: Antitumor Mechanism Underlying the Effects Of Tetramethylpyrazine In Multiple Organsmentioning

confidence: 99%

Tetramethylpyrazine: A Review of Its Antitumor Potential and Mechanisms

Yang

Dai

et al. 2021

Front. Pharmacol.

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Cancer remains a major public health threat. The mitigation of the associated morbidity and mortality remains a major research focus. From a molecular biological perspective, cancer is defined as uncontrolled cell division and abnormal cell growth caused by various gene mutations. Therefore, there remains an urgent need to develop safe and effective antitumor drugs. The antitumor effect of plant extracts, which are characterized by relatively low toxicity and adverse effect, has attracted significant attention. For example, increasing attention has been paid to the antitumor effects of tetramethylpyrazine (TMP), the active component of the Chinese medicine Chuanqiong, which can affect tumor cell proliferation, apoptosis, invasion, metastasis, and angiogenesis, as well as reverse chemotherapeutic resistance in neoplasms, thereby triggering antitumor effects. Moreover, TMP can be used in combination with chemotherapeutic agents to enhance their effects and reduce the side effect associated with chemotherapy. Herein, we review the antitumor effects of TMP to provide a theoretical basis and foundation for the further exploration of its underlying antitumor mechanisms and promoting its clinical application.

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“…The underlying mechanisms involve inhibition of platelet aggregation, suppression of apoptosis, and scavenging peroxyl radicals, superoxide, and hydroxyl radicals[ 8 ]. Recent studies have demonstrated that TMP has potent inhibitory effects on a number of types of tumors, such as lung, breast, ovarian carcinoma, gastric carcinoma, osteosarcoma, leukemia, and hepatocellular carcinoma, through affecting the proliferation and apoptosis of tumor cells[ 9 - 13 ]. However, the effects of TMP on colon cancer have not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Tetramethylpyrazine inhibits proliferation of colon cancer cells in vitro

Hou

et al. 2021

WJCC

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BACKGROUND Colon cancer is one of the most common malignancies worldwide, and chemotherapy is a widely used strategy in colon cancer clinical therapy. However, chemotherapy resistance is a major cause of disease recurrence and progression in colon cancer, and thus novel drugs for treatment are urgently needed. Tetramethylpyrazine (TMP), a component of the traditional Chinese medicine Chuanxiong Hort, has been proven to exhibit a beneficial effect in tumors. AIM To investigate the potential anticancer activity of TMP in colon cancer and its underlying mechanisms. METHODS Colon cancer cells were incubated with different concentrations of TMP. Cell viability was evaluated by crystal violet staining assay and cell counting kit-8 assay, and cell apoptosis and cell cycle were assessed by flow cytometry. RESULTS TMP significantly inhibited the proliferation of colon cancer cells in a dose- and time-dependent manner. In addition, flow cytometry revealed that TMP induced cell cycle arrest at the G0/G1 phase. TMP treatment caused early stage apoptosis in SW480 cells, whereas it caused late stage apoptosis in HCT116 cells. CONCLUSION Our studies demonstrated that TMP inhibits the proliferation of colon cancer cells in a dose- and time-dependent manner by inducing apoptosis and arresting the cell cycle at the G0/G1 phase. Our findings suggest that TMP might serve as a potential novel therapeutic drug in the treatment of human colon cancer.

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Tetramethylpyrazine (TMPZ) triggers S-phase arrest and mitochondria- dependent apoptosis in lung cancer cells

Cited by 16 publications

References 28 publications

Ligustrazine induces the colorectal cancer cells apoptosis via p53-dependent mitochondrial pathway and cell cycle arrest at the G0/G1 phase

Ligustrazine induces the colorectal cancer cells apoptosis via p53-dependent mitochondrial pathway and cell cycle arrest at the G0/G1 phase

Tetramethylpyrazine: A Review of Its Antitumor Potential and Mechanisms

Tetramethylpyrazine inhibits proliferation of colon cancer cells in vitro

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