Upregulation of miR-34a by diallyl disulfide suppresses invasion and induces apoptosis in SGC-7901 cells through inhibition of the PI3K/Akt signaling pathway

Wang, Guojun; Liu, Guanghui; Ye, Yanwei; Fu, Yang; Zhang, Xiefu

doi:10.3892/ol.2016.4266

Cited by 29 publications

(15 citation statements)

References 42 publications

(49 reference statements)

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“…PI3K/AKT signaling pathway is deregulated in various cancers, which plays a key role in cell survival and proliferation, glucose metabolism, apoptosis, adhesion and metastasis (38). DADS was found to cause a significant reduction in the invasion of SGc-7901 cells by upregulating miR-34a, via the inhibition of the PI3K/AKT signaling pathway (39). Our data are consistent with this concept.…”

Section: Discussionsupporting

confidence: 84%

Diallyl disulfide inhibits the metastasis of type Ⅱ esophageal‑gastric junction adenocarcinoma cells via NF-κB and PI3K/AKT signaling pathways in vitro

et al. 2017

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Esophageal-gastric junction adenocarcinoma (AEG) is an aggressive tumor with high incidence and dismal prognosis worldwide. Despite significant advances in therapeutic strategies, the 5-year survival rate still remains low. Diallyl disulfide (DADS), which is one of the major volatile components isolated from garlic, has been shown to have multi-targeted antitumor activities in a variety of cancer cells. However, the exact anti-metastatic effects and underlying molecular mechanisms of DADS in AEG have not been elucidated. The present study demonstrated that DADS inhibited cell viability of OE19 cells with low cytotoxicity to healthy hepatocytes, L02 cells, in vitro. Non-toxic doses of DADS were ≤10 µg/ml for a 24-h treatment. Our data showed that these non-toxic doses of DADS were found to block the metastasis of OE19 cells by suppressing MMPs, increasing u-PA and TIMPs, as well as altering the balance of MMPs/TIMPs, which at least in part resulted from the suppression of NF-κB and PI3K/AKT signaling pathways. The present study provides a previously neglected insight into the investigation of DADS in suppressing tumor metastasis and its underlying molecular mechanisms in vitro. Hence, DADS could be a promising anticancer agent for anti-metastatic treatment of AEG in the future.

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Section: Discussionsupporting

confidence: 84%

Diallyl disulfide inhibits the metastasis of type Ⅱ esophageal‑gastric junction adenocarcinoma cells via NF-κB and PI3K/AKT signaling pathways in vitro

et al. 2017

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“…DADS can silence HIF-1α (hypoxia inducible factor 1α) via increasing expression of miR-22 to repress VEGF (vascular endothelial growth factor) expression to block angiogenesis, leading to the disruption of cancer progression [79,84]. The upregulation of miR-22 induced by DADS may post-transcriptionally target cyclin A2 and CDKN1A (cyclin-dependent kinase inhibitor 1A) to arrest the cell cycle in G0/G1 phage in CRC and liver cancer cells, respectively [85,86]. The recent researches have confirmed that DADS induces apoptosis of SGC-7901 cells by upregulation of miR-34a, via inhibition of the PI3K-Akt signaling pathway [87].…”

Section: Regulation Of the Mirnas By Dadsmentioning

confidence: 99%

The Progress of Diallyl Disulfide in Anti-Cancer

Lz¹,

Liao²,

Wang³

et al. 2017

Chemotherapy

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Considerable evidence in recent years suggests that garlic has anti-proliferative effects on various types of cancer. Garlic contains water-soluble and oil-soluble sulfur compounds. Oil-soluble compounds (OSCs), such as diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS) and ajoene are more effective than watersoluble compounds in protection against cancer. DADS, a major organosulfur compound derived from garlic, can reduce carcinogen-induced cancers in experimental animals and inhibit the proliferation of various types of cancer cells. The mechanisms of these action of DADS include activation of metabolic enzymes that detoxify carcinogens, suppression of the formation of DNA adducts, antioxidant effects, regulation of cell-cycle progression, induction of apoptosis, and inhibition of angiogenesis and metastasis. These topics are discussed in depth in this review.

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“…Among these miRNAs, miR-34a is significantly downregulated in chemoresistant prostate cancer cell line (3) or CD44 + cancer stem cells (4). As a tumor suppressor miRNA, miR-34a is responsible for promoting tumor cell apoptosis, inhibiting tumor metastasis (5) and chemoresistance (6). Thus, miR-34a replenishment might be a novel therapeutic method to reverse PTX-resistance for the treatment of chemoresistant prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Micellar Delivery of miR-34a Modulator Rubone and Paclitaxel in Resistant Prostate Cancer

et al. 2017

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Treatment of prostate cancer with paclitaxel (PTX) often fails due to development of chemoresistance caused by downregulation of the tumor suppressor gene miR-34a. In this study, we demonstrate that co-delivery of PTX and 2′-hydroxy-2,4,4′,5,6′-pentamethoxychalcone (termed rubone) drives upregulation of miR-34a and chemosensitizes PTX-resistant prostate cancer cells, killing both cancer stem-like cells (CSCs) and bulk tumor cells. Rubone upregulated miR-34a and reversed its downstream target genes in DU145-TXR and PC3-TXR cells. PTX and rubone combination therapy inhibited tumor cell growth, migration, and CSC population growth. We synthesized poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-dodecanol) (PEG-PCD) to prepare micelles. The drug-loading capacities were 9.70 ± 0.10% and 5.34 ± 0.02% for PTX and rubone, respectively, controlling a drug release of 60.20 ± 2.67% and 60.62 ± 4.35% release of PTX and rubone at 24 h. Delivery of miR-34a and rubone decreased PC3-TXR cell viability with increasing PTX concentration. Co-incubation with a miR-34a inhibitor diminished the effect of rubone. PTX IC50 in PC3 and PC3-TXR cells was 55.6 and 2580 nM, respectively, but decreased to 49.8 and 93.2 nM when treated in combination with rubone, demonstrating a reversal of PTX resistance by rubone. Systemic administration of micelles carrying PTX and rubone inhibited orthotopic prostate tumor growth in nude mice, compared to monotherapy, by reversing the expression of miR-34a, SIRT1, Cyclin D1 and E-cadherin. In summary, our results showed how rubone acts as an efficient small molecule modulator of miR-34a to reverse chemoresistance and further enhance the therapeutic efficacy of PTX in PTX-resistant prostate cancer.

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Upregulation of miR-34a by diallyl disulfide suppresses invasion and induces apoptosis in SGC-7901 cells through inhibition of the PI3K/Akt signaling pathway

Abstract: Abstract. Diallyl disulfide (DADS) exerts anticarcinogenic activity in various types of cancer. However, the mechanism underlying its anticarcinogenic activity remains to be elucidated.

Cited by 29 publications

References 42 publications

Diallyl disulfide inhibits the metastasis of type Ⅱ esophageal‑gastric junction adenocarcinoma cells via NF-κB and PI3K/AKT signaling pathways in vitro

Diallyl disulfide inhibits the metastasis of type Ⅱ esophageal‑gastric junction adenocarcinoma cells via NF-κB and PI3K/AKT signaling pathways in vitro

The Progress of Diallyl Disulfide in Anti-Cancer

Micellar Delivery of miR-34a Modulator Rubone and Paclitaxel in Resistant Prostate Cancer

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