Diallyl disulfide induces G2/M arrest and promotes apoptosis through the p53/p21 and MEK-ERK pathways in human esophageal squamous cell carcinoma

Yin, Xiaonan; Zhang, Rong; Feng, Cheng; Zhang, Jun; Liu, Dong; Xu, Kun; Wang, Xijing; Zhang, Shuqun; Li, Zongfang; Liu, Xinlian; Ma, Hongbing

doi:10.3892/or.2014.3361

Cited by 49 publications

(37 citation statements)

References 26 publications

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“…31 Some studies have reported that ERK-or JNK/MAPK activation induces G2/M phase arrest and apoptosis in solid tumors. [32][33][34][35][36] We found that palbociclib destabilizes HIF-1a and activates ERK1/2 under either normoxic or hypoxic conditions (Fig. 3).…”

Section: Discussionmentioning

confidence: 78%

The CDK4/6 inhibitor palbociclib synergizes with irinotecan to promote colorectal cancer cell death under hypoxia

et al. 2017

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Hypoxia is an inherent impediment to cancer therapy. Palbociclib, a highly selective inhibitor for CDK4/6, has been tested in numerous clinical trials and has been approved by the FDA. We previously reported that CDK inhibitors can destabilize HIF1a regardless of the presence of hypoxia and can sensitize tumor cells to TRAIL through dual blockade of CDK1 and GSK-3b. To translate this knowledge into a cancer therapeutic strategy, we investigated the therapeutic effects and molecular mechanisms of CDK inhibition against colon cancer cells under normoxia and hypoxia. We found that palbociclib sensitizes colon cancer cells to hypoxia-induced apoptotic resistance via deregulation of HIF-1a accumulation. In addition to inhibition of cell proliferation, we observed that palbociclib promotes colon cancer cell death regardless of the presence of hypoxia at a comparatively high concentration via regulating ERK/GSK-3b signaling and GSK-3b expression. Furthermore, palbociclib synergized with irinotecan in a variety of colon cancer cell lines with various molecular subtypes via deregulating irinotecan-induced Rb phosphorylation and reducing HIF-1a accumulation under normoxia or hypoxia. Collectively, our findings provide a novel combination therapy strategy against hypoxic colon cancer cells that may be further translated in the clinic.

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Section: Discussionmentioning

confidence: 78%

The CDK4/6 inhibitor palbociclib synergizes with irinotecan to promote colorectal cancer cell death under hypoxia

et al. 2017

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“…Previous studies have demonstrated that oncogenes, such as p53, c-Myc, matrix metallopepti- dase 9 and human sterile alpha motif domain-containing 9, are abnormally expressed in ESCC tissues (22)(23)(24). Furthermore, increased expression levels of transforming growth factor-β may stimulate the PTEN/PI3K pathway and promote epithelial-mesenchymal transition in the human esophageal epithelium (25).…”

Section: Discussionmentioning

confidence: 99%

Low expression of microRNA-202 is associated with the metastasis of esophageal squamous cell carcinoma

Zhang

Dong

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The present study aimed to determine the expression levels and biological functions of in patients with esophageal squamous cell carcinoma (ESCC). A total of 60 patients with ESCC and 30 healthy individuals were enrolled and reverse transcription-quantitative polymerase chain reaction was performed to measure the expression levels of miR-202. In order to investigate the effects of miR-202 expression levels on the proliferative, migratory and invasive abilities of ESCC cells, methylthiazolyl-tetrazolium bromide proliferation, in vitro scratch and Transwell ® chamber assays were performed. Expression levels of miR-202 were significantly decreased in the peripheral blood of patients with ESCC, which is associated with the degree of cell differentiation and lymph node metastasis (P<0.05). Following miR-202 transfection, cell proliferation was significantly inhibited (P<0.05). Cell migration and invasion was also significantly inhibited by miR-202 transfection (P<0.05). The results of the present study demonstrated that the expression of miR-202 inhibited the proliferation, migration and invasion of ESCC cells. Furthermore, low expression levels of miR-202 were detected in the peripheral blood of patients with ESCC, which is associated with the development, invasion and metastasis of ESCC.

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“…G 2 /M phase arrest was induced by diallyl disulfide by decreasing cyclin B1, CDC2, p-CDC2 and cdc25c, and activating the p53/p21 pathway. Apoptosis was induced by diallyl disulfide through activation of caspases, alteration of Bax/Bcl-2 balance and suppression of the MEK-ERK pathway [151]. The results were also verified in human esophageal carcinoma ECA109 cells and in mice [152].…”

Section: Garlicmentioning

confidence: 97%

Spices for Prevention and Treatment of Cancers

et al. 2016

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Spices have been widely used as food flavorings and folk medicines for thousands of years. Numerous studies have documented the antioxidant, anti-inflammatory and immunomodulatory effects of spices, which might be related to prevention and treatment of several cancers, including lung, liver, breast, stomach, colorectum, cervix, and prostate cancers. Several spices are potential sources for prevention and treatment of cancers, such as Curcuma longa (tumeric), Nigella sativa (black cumin), Zingiber officinale (ginger), Allium sativum (garlic), Crocus sativus (saffron), Piper nigrum (black pepper) and Capsicum annum (chili pepper), which contained several important bioactive compounds, such as curcumin, thymoquinone, piperine and capsaicin. The main mechanisms of action include inducing apoptosis, inhibiting proliferation, migration and invasion of tumors, and sensitizing tumors to radiotherapy and chemotherapy. This review summarized recent studies on some spices for prevention and treatment of cancers, and special attention was paid to bioactive components and mechanisms of action.

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Diallyl disulfide induces G2/M arrest and promotes apoptosis through the p53/p21 and MEK-ERK pathways in human esophageal squamous cell carcinoma

Cited by 49 publications

References 26 publications

The CDK4/6 inhibitor palbociclib synergizes with irinotecan to promote colorectal cancer cell death under hypoxia

The CDK4/6 inhibitor palbociclib synergizes with irinotecan to promote colorectal cancer cell death under hypoxia

Low expression of microRNA-202 is associated with the metastasis of esophageal squamous cell carcinoma

Spices for Prevention and Treatment of Cancers

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