Harmine combined with paclitaxel inhibits tumor proliferation and induces apoptosis through down-regulation of cyclooxygenase-2 expression in gastric cancer

Yu, Xintong; Sun, Kai; Tang, Xiao‐He; Zhou, Cun‐Jin; Sun, Haiguo; Yan, Zhe; Fang, Ling; Wu, Hong‐Wen; Xie, Yuan; Gu, Bin

doi:10.3892/ol.2016.4696

Cited by 18 publications

(8 citation statements)

References 21 publications

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“…Many anticancer drugs function by inducing apoptosis. 1 , 2 Paclitaxel induces apoptosis in different cancer cells, including breast cancer, 23 gastric cancer, 43 colon cancer, 44 and leukemia cells 45 by modifying mitochondrial transition permeability, activating caspase-8 and caspase-3, 44 , 46 and Bcl-2 inactivation by a mechanism that may involve the binding of paclitaxel to this antiapoptotic protein. 47 As demonstrated in this study, heat-killed baker’s yeast also acts as an anticancer agent via induction of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Baker’s Yeast Sensitizes Metastatic Breast Cancer Cells to Paclitaxel In Vitro

et al. 2017

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Our earlier studies have demonstrated that phagocytosis of baker’s yeast (Saccharomyces cerevisiae) induces apoptosis in different cancer cell lines in vitro and in vivo. This study aimed to examine how baker’s yeast sensitizes murine and human breast cancer cells (BCC) to paclitaxel in vitro. This sensitizing effect makes lower concentrations of chemotherapy more effective at killing cancer cells, thereby enhancing the capacity of treatment. Three BCC lines were used: the metastatic murine 4T1 line, the murine Ehrlich ascites carcinoma (EAC) line, and the human breast cancer MCF-7 line. Cells were cultured with different concentrations of paclitaxel in the presence or absence of baker’s yeast. Cell survival and the IC50 values were determined by MTT assay and trypan blue exclusion method. Percent of DNA damage, apoptosis, and cell proliferation were examined by flow cytometry. Yeast alone and paclitaxel alone significantly decreased 4T1 cell viability postculture (24 and 48 hours), caused DNA damage, increased apoptosis, and suppressed cell proliferation. Baker’s yeast in the presence of paclitaxel increased the sensitivity of 4T1 cells to chemotherapy and caused effects that were greater than either treatment alone. The chemosensitizing effect of yeast was also observed with murine EAC cells and human MCF-7 cells, but to a lesser extent. These data suggest that dietary baker’s yeast is an effective chemosensitizer and can enhance the apoptotic capacity of paclitaxel against breast cancer cells in vitro. Baker’s yeast may represent a novel adjuvant for chemotherapy treatment.

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Section: Discussionmentioning

confidence: 99%

Baker’s Yeast Sensitizes Metastatic Breast Cancer Cells to Paclitaxel In Vitro

et al. 2017

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“…The anticancer activity of harmine in human cancers has been evidenced. Harmine induces proliferation inhibition, apoptosis and pro-death autophagy in gastric cells, and shows synergistic effects with paclitaxel [57,58]. However, the efficiency, sensitivity and specificity of these compounds in the 10 NSCLC patients should be further validated in clinical practices.…”

Section: Discussionmentioning

confidence: 99%

Patient-derived organoids of non-small cells lung cancer and their application for drug screening

Li¹,

Gao²,

Liang³

et al. 2020

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Patient-derived organoids (PDOs) are emerging as preclinical models with promising values in personalized cancer therapy. The purpose of this study was to establish a living biobank of PDOs from patients with non-small cell lung cancer (NSCLC) and to study the responses of PDOs to drugs. PDOs derived from NSCLC were cultured in vitro, and then treated with natural compounds including chelerythrine chloride, cantharidin, harmine, berberine and betaine with series of concentrations (0.5-30 μM) for drug screening. Phenotypic features and treatment responses of established PDOs were reported. Cell lines (H1299, H460 and H1650) were used for drug screening. We successfully established a living NSCLC organoids biobank of 10 patients, which showed similar pathological features with primary tumors. Nine of the 10 patients showed mutations in EGFR. Natural compounds chelerythrine chloride, cantharidin and harmine showed anticancer activity on PDOs and cell lines. There was no significant difference in the 95% confidence interval (CI) for the IC50 value of chelerythrine chloride between PDOs (1.56-2.88 μM) and cell lines (1.45-3.73 μM, p>0.05). PDOs were sensitive to berberine (95% CI, 0.092-1.55 μM), whereas cell lines showed a resistance (95% CI, 46.57-2275 μM, p<0.0001). PDOs had a higher IC50 value of cantharidin, and a lower IC50 value of harmine than cell lines (p<0. 05, μM in cell lines, respectively). Both PDOs and cell lines were resistant to betaine. Chelerythrine chloride showed the highest inhibitory effect in both models. Our study established a living biobank of PDOs from NSCLC patients, which might be used for high-throughput drug screening and for promising personalized therapy design.

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“…The top two inhibitory compounds were "harmine," a drug for Parkinson's disease, and "chrysin," an antifungal drug. A search of the literature showed that harmine induces the apoptosis of gastric cancer cells by down-regulating cyclooxygenase-2 (COX-2) expression (Yu et al, 2016) and that chrysin inhibits COX-2 expression in macrophages and induces Akt inactivation in U937 cells (Woo, Jeong, Inoue, Park, & Kwon, 2005). Thus, COX-2 is a common target of harmine and chrysin.…”

Section: Cyclooxygenase-2 Is Essential For the Apical Extrusion Of mentioning

confidence: 99%

Prostaglandin E₂ and its receptor EP2 trigger signaling that contributes to YAP‐mediated cell competition

et al. 2020

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Cell competition is a biological process by which unfit cells are eliminated from “cell society.” We previously showed that cultured mammalian epithelial Madin‐Darby canine kidney (MDCK) cells expressing constitutively active YAP were eliminated by apical extrusion when surrounded by “normal” MDCK cells. However, the molecular mechanism underlying the elimination of active YAP‐expressing cells was unknown. Here, we used high‐throughput chemical compound screening to identify cyclooxygenase‐2 (COX‐2) as a key molecule triggering cell competition. Our work shows that COX‐2‐mediated PGE2 secretion engages its receptor EP2 on abnormal and nearby normal cells. This engagement of EP2 triggers downstream signaling via an adenylyl cyclase‐cyclic AMP‐PKA pathway that, in the presence of active YAP, induces E‐cadherin internalization leading to apical extrusion. Thus, COX‐2‐induced PGE2 appears a warning signal to both abnormal and surrounding normal cells to drive cell competition.

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Harmine combined with paclitaxel inhibits tumor proliferation and induces apoptosis through down-regulation of cyclooxygenase-2 expression in gastric cancer

Cited by 18 publications

References 21 publications

Baker’s Yeast Sensitizes Metastatic Breast Cancer Cells to Paclitaxel In Vitro

Baker’s Yeast Sensitizes Metastatic Breast Cancer Cells to Paclitaxel In Vitro

Patient-derived organoids of non-small cells lung cancer and their application for drug screening

Prostaglandin E₂ and its receptor EP2 trigger signaling that contributes to YAP‐mediated cell competition

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Harmine combined with paclitaxel inhibits tumor proliferation and induces apoptosis through down-regulation of cyclooxygenase-2 expression in gastric cancer

Cited by 18 publications

References 21 publications

Baker’s Yeast Sensitizes Metastatic Breast Cancer Cells to Paclitaxel In Vitro

Baker’s Yeast Sensitizes Metastatic Breast Cancer Cells to Paclitaxel In Vitro

Patient-derived organoids of non-small cells lung cancer and their application for drug screening

Prostaglandin E2 and its receptor EP2 trigger signaling that contributes to YAP‐mediated cell competition

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Prostaglandin E₂ and its receptor EP2 trigger signaling that contributes to YAP‐mediated cell competition