Matrine suppresses proliferation and induces apoptosis in human cholangiocarcinoma cells through suppression of JAK2/STAT3 signaling

Yang, Nanying; Han, Feng; Cui, Hong; Huang, Jinxi; Wang, Tao; Zhou, Yi; Zhou, Jinxue

doi:10.1016/j.pharep.2014.10.016

Cited by 46 publications

(28 citation statements)

References 27 publications

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“…Previous studies have shown that matrine may be used as one type of antitumor drug for leukemia and lung, liver, gastric, breast and cervical cancers, as well as numerous other types of malignant tumors with high drug resistant activity (14,15). The present study confirmed that certain concentrations of matrine could significantly inhibit the proliferation and invasion of the human hepatocellular carcinoma (HCC) cell line (16,17). However, to the best of our knowledge, the effect and mechanism of matrine on hepatic cancer stem cells in vitro has not yet been reported.…”

Section: Introductionsupporting

confidence: 80%

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Antitumor effects of matrine on cancer stem like cells isolated from the human liver cancer SMMC‑7721 cell line

et al. 2017

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Abstract. The existence of cancer stem cells (CSCs) or cancer stem-like cells (CSLCs) is regarded as the cause of tumor formation and recurrence. Matrine has been reported to exhibit antitumor effects in cancer cells. In the present study, a preliminary study was performed on the mechanisms of matrine on hepatocellular carcinoma (HCC) stem-like cells. The HCC SMMC-7721 cell line was cultured in tumor stem cell-specific medium to form spheres, and different concentrations (1, 2 and 5 mg/kg) of cisplatin were then used in order to purify the most drug-resistant cells, which were used as CSLCs. An MTT assay was performed to detect the inhibitory effects of matrine against CSLC proliferation. Quantitative polymerase chain reaction (qPCR) and western blot analysis were used to detect changes in cell adhesion regulating gene (CAR), E-cadherin, laminin and fibronectin. As a result, using tryptose sulfite cycloserine medium culture and cisplatin-resistance screening, CSLCs were successfully isolated from the SMMC-7721 cell line. Matrine inhibited the proliferation of CSLCs in vitro. The results of qPCR and western blot analysis demonstrated that matrine upregulated the expression of CAR, E-cadherin, laminin and fibronectin in CSLCs compared with the control treatment. A certain concentration of matrine exhibited antitumor effects on HCC stem like cells.

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Section: Introductionsupporting

confidence: 80%

“…Previous studies have suggested that matrine may eliminate tumor cells by apoptosis induction (20,21). Ma et al (22) demonstrated that matrine significantly inhibited the invasion of human pancreatic cancer cells by downregulating the expression of membrane type 1-matrix metalloproteinase.…”

Section: Discussionmentioning

confidence: 99%

Antitumor effects of matrine on cancer stem like cells isolated from the human liver cancer SMMC‑7721 cell line

et al. 2017

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“…Matrine, a traditional Chinese medicine, is an alkaloid isolated from plants in the genus Sophora , comprised of four rings of quinolizidine classes (C 15 H 24 N 2 O). Matrine exhibits different biological properties, including anti-inflammatory (16), antitumor (17), anti-viral (18), anti-fibrosis (19), anti-arrhythmia (20), anti-asthmatic (21) and immunosuppressive activity (22). However, the effects of matrine on the proliferation and apoptosis of FLS have yet to be reported.…”

Section: Introductionmentioning

confidence: 99%

Matrine induces the apoptosis of fibroblast-like synoviocytes derived from rats with collagen-induced arthritis by suppressing the activation of the JAK/STAT signaling pathway

Yang

Dong

2016

International Journal of Molecular Medicine

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The induction of apoptosis-resistant rheumatoid synovial tissue cells has been related to constitutively active Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling in rheumatoid arthritis (RA). The excessive proliferation and inherent resistance to apoptosis of fibroblast-like synoviocytes (FLS) is an important mechanism by which RA originates. However, the effects of matrine on FLS in RA is unclear. The present study aimed to investigate the mechanism of action of matrine in a rat model of collagen-induced arthritis (CIA). The CIA model was established using bovine type II collagen. FLS were isolated from control and CIA rats, cultured in vitro, and confirmed to harbor fibroblast-like characteristics. After treatment of FLS with varying concentrations of matrine, the JAK2 inhibitor AG490, or a combination of both drugs, cell proliferation, apoptosis rate, expression of apoptotic markers and the activation of the JAK/STAT pathway were assessed. Additionally, CIA rats were administered either matrine or methotrexate by oral gavage to examine the effects of therapeutic intervention on arthritis pathogenesis. The arthritis index (AI) was measured and ankle joint structure was analyzed histologically to determine the severity of CIA. Furthermore, expression levels of apoptotic markers and members of the JAK/STAT family were also examined in vivo. Compared with the CIA group, matrine reduced AI and improved ankle pathology. Matrine also inhibited FLS proliferation, induced G0/G1 cell cycle arrest, and increased the rate of apoptosis in vitro. The effects of matrine on apoptosis induction were further confirmed by observations that Bcl-2 levels were decreased, whereas Bax and caspase-3 levels were increased in the matrine-treated synovial tissues and FLS. Finally, matrine treatment also diminished the phosphorylation, and hence activation of JAK2, STAT1 and STAT3. Our results suggest that matrine induces the apop-tosis of FLS from rats with CIA by inhibiting activation of the JAK/STAT signaling pathway.

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“…It has been reported that the formulation has physiological functions, such as improving gastrointestinal function, strengthening the immune system, and speeding up the production of red blood cells (29). This formulation can also be used for the treatment of malignant tumors (9). However, in the context of evidence-based medicine, the determination of efficacy requires critical evaluation using modern medical research approaches.…”

Section: Discussionmentioning

confidence: 99%

“…Indigo jade red is used in the treatment of chronic myelogenous leukemia and can significantly inhibit tumor growth (4,5). Matrine is able to inhibit the growth of a variety of solid tumors, and has exhibited activity against pancreatic cancer, breast cancer, lung cancer and bile duct cancer cells (6)(7)(8)(9). In recent years, increasing numbers of Chinese herbal medicines or prescriptions have gained international recognition and acceptance for their anticancer effects (10).…”

Section: Introductionmentioning

confidence: 99%

Sijunzi decoction‑treated rat serum induces apoptosis of side population cells in gastric carcinoma

et al. 2017

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Abstract. Sijunzi decoction (SJZD) is a traditional Chinese herbal medicine. Previous studies have indicated that SJZD exhibits antitumor activity. However, the underlying molecular mechanism has not been fully elucidated. To explore the antitumor mechanism of SJZD, the effects of serum from rats treated with SJZD on the proliferation of MKN-28 and HGC-27 gastric carcinoma cell lines were systematically investigated. It was found that SJZD-treated rat serum significantly inhibited the growth of MKN-28 and HGC-27 cells in vitro. The results obtained from a colony formation assay showed that SJZD-treated rat serum decreased the colony formation ability of MKN-28 and HGC-27 cells. The apoptosis rate in MKN-28 and HGC-27 cells was also increased following treatment with SJZD-treated rat serum. Flow cytometry with cell sorting revealed the presence of side population (SP) cells in MKN-28 and HGC-27 cells though Hoechst 33342 staining, and verapamil reduced the SP percentage. Further analysis showed that SJZD-treated rat serum promoted the apoptosis of SP cells in MKN-28 and HGC-27 cell lines by upregulating Bax, caspase-3 and PARP and downregulating bcl-2. These data revealed the therapeutic effect of SJZD-treated rat serum on gastric carcinoma. Following the preliminary identification of the inhibitory effect on the growth of gastric cancer cells in vitro, the growth inhibitory effect of SJZD-treated rat serum on SP cells was confirmed, and this inhibition particularly involved the induction of cell apoptosis.

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Matrine suppresses proliferation and induces apoptosis in human cholangiocarcinoma cells through suppression of JAK2/STAT3 signaling

Abstract: Matrine can trigger mitochondrial apoptotic death of cholangiocarcinoma cells largely through inhibition of JAK2/STAT3 signaling. Therefore, matrine represents a potentially effective anticancer agent for cholangiocarcinoma.

Cited by 46 publications

References 27 publications

Antitumor effects of matrine on cancer stem like cells isolated from the human liver cancer SMMC‑7721 cell line

Antitumor effects of matrine on cancer stem like cells isolated from the human liver cancer SMMC‑7721 cell line

Matrine induces the apoptosis of fibroblast-like synoviocytes derived from rats with collagen-induced arthritis by suppressing the activation of the JAK/STAT signaling pathway

Sijunzi decoction‑treated rat serum induces apoptosis of side population cells in gastric carcinoma

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