Phenethyl isothiocyanate suppresses cervical carcinoma metastasis potential and its molecular mechanism

Zhang, Li; Qin, Hao; Bao, Lewen; Liu, Wenxin; Fu, Xin; Chen, Ying; Wu, Huijuan

doi:10.3892/mmr.2014.2565

Cited by 12 publications

(9 citation statements)

References 17 publications

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“…It activates downstream target genes, including IL-6, IL-8, cyclin D and Bcl-2. A previous study suggests that the downstream target genes may play an important role in cervical cancer cell metastasis (28). Our results provide evidence that ATAD2 is not only important in cervical cancer cell proliferation, but is also involved in cervical cancer cell invasion and migration.…”

Section: Discussionsupporting

confidence: 71%

Oncogene ATAD2 promotes cell proliferation, invasion and migration in cervical cancer

Zheng

Zhang

et al. 2015

Oncology Reports

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The ATPase family AAA domain-containing protein 2 (ATAD2) is associated with many cellular processes, such as cell proliferation, invasion and migration. However, the molecular biological function of the ATAD2 gene in cervical cancer is unclear. The purpose of this study was to explore ATAD2 expression in cervical cancer, evaluate the relationship between the development of cervical cancer, metastasis and clinicopathological characteristics, and discuss the implications for its use in clinical treatment. Protein and mRNA expression of ATAD2 was examined in tissues and cell lines. Tumor tissues from 135 cases of cervical cancer were collected for evaluation of ATAD2 expression by immunohistochemistry and western blotting. Prognostic significance was evaluated by the Cox hazards model and Kaplan-Meier survival method. HeLa and SiHa cells were transfected with two siRNAs targeting ATAD2. ATAD2 knockdown was used to analyze cell proliferation, invasion and migration. Cell viability was evaluated with the Cell Counting Κit-8 (CCK-8) assay, cell invasion by a Transwell assay and cell migration by a wound healing/scratch migration assay. ATAD2 was shown to be highly expressed in cervical cancer tissues, both at the transcriptional and protein levels, and was correlated with poor patient survival (P<0.05). Knockdown of ATAD2 in the HeLa and SiHa cells was found to reduce the capacity for invasion and migration (P<0.05), and inhibited the growth and clonogenic potential of the HeLa and SiHa cell lines. Our results suggest that cervical cancer tissues may have highly expressed ATAD2, which is associated with tumor stage and lymph node status (P<0.05). Oncogene ATAD2 may play an important role in cervical cancer proliferation, invasion and migration. It could serve as a prognostic marker and a therapeutic target for cervical cancer.

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Section: Discussionsupporting

confidence: 71%

Oncogene ATAD2 promotes cell proliferation, invasion and migration in cervical cancer

Zheng

Zhang

et al. 2015

Oncology Reports

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“…Our previous study showed that PEITC and BITC suppress metastasis potential of lung cancer cells . Interestingly, other groups also revealed the inhibitory effect of isothiocyanates on metastasis in ovarian cancer, prostate cancer, breast cancer, and cervical carcinoma . Although these studies indicated that several mechanisms are involved, such as the inhibition of CRM1‐mediated nuclear export and mTOR‐STAT3 pathway, regulation on miRNA‐194, and involvement of HIF‐1alpha, however, the role of autophagy has not been elucidated.…”

Section: Discussionmentioning

confidence: 98%

Inhibition of autophagy potentiates the anti‐metastasis effect of phenethyl isothiocyanate through JAK2/STAT3 pathway in lung cancer cells

Wang

Cao

et al. 2018

Molecular Carcinogenesis

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Phenethyl isothiocyanate (PEITC) is a natural compound abundant in cruciferous vegetables. PEITC possesses anti-tumor effect in various human malignances. Our previous study has shown that benzyl isothiocyanates (BITC) induce autophagy in lung cancer cells. However, whether autophagy play a role in the inhibitory effect of PEITC on lung cancer metastasis is unclear. In this study, we found that PEITC suppressed migration and invasion of lung cancer cells by regulating MMP2. It also induced autophagy, evidenced by the formation of acidic vesicular organelles (AVOs), the punctate pattern of LC3, the accumulation of LC3-II, and the expression of Beclin-1. Inhibition of autophagy by 3-MA and chloroquine (CQ) or knock down of Beclin-1 enhanced PEITC-caused metastasis inhibition. JAK2/STAT3 pathway was suppressed by PEITC, and further inhibited by 3-MA and CQ or Beclin-1 knock down, as a result of decreased expression of p-JAK2 and p-STAT3. Blocking JAK2/STAT3 pathway by inhibitor AG490 and Stattic suppressed cell migration and decreased the expression of MMP2, MMP9, Twist, and c-Myc. Further in vivo study showed that PEITC inhibited tumor growth, induced autophagy and suppressed JAK2/STAT3 pathway, and inhibitor CQ enhanced this effect. Taken together, our results demonstrate that PEITC inhibits metastasis potential of lung cancer cells, and induces autophagy. The autophagy induced by PEITC preserves metastasis potential of lung cancer cells, via activation of JAK2/STAT3 pathway. Inhibition of autophagy enhanced the inhibitory effect of PEITC on metastasis potential of lung cancer cells. Our finding suggests that targeting autophagy could be a promising strategy for anti-metastasis therapies.

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“…It was considered to act via the transforming growth factor (TGF)β/Smad2 pathway, evident by increasing TGFβ, IL6, and IL8 production and Smad2 phosphorylation. 116 In another study, phenethyl isothiocyanate was demonstrated to have cytotoxic potential against OVCAR-3 cells by its anti-proliferative effect in a dosedependent manner. Apoptosis induction was through caspase-3 and -9 activation.…”

Section: 73mentioning

confidence: 98%

The Role of Secondary Metabolites on Gynecologic Cancer Therapy: Some Pathways and Mechanisms

Demırel¹,

Süntar²

2017

tjps

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ÖZJinekolojik kanserler insanlarda ve hayvanlarda en yaygın görülen kanserler arasındadır. Tedavi başarısı tanıdaki evre, tümör tipi, orijini ve metastazı içeren birçok faktöre bağlıdır. Günümüzde bu kanserlerin tedavisinde, cerrahi müdahale, kemoterapi ve radyoterapi uygulanmaktadır. Ancak, birçok anti-karsinojenik ilaç ciddi yan etkilere neden olabilir ve ayrıca tedaviye beklenen yanıt alınamayabilir. Son yıllarda yapılan çalışmalarda kanser ve inflamasyon arasındaki ilişkinin önemi vurgulanmıştır. Ve bununla birlikte, inflamatuvar yolaklara karşı yararlı biyoaktif etkiler gösteren birçok fitokimyasalın jinekolojik kanser tedavisi için antikarsinojenik potansiyele sahip olduğu kanıtlanmıştır. Bu derlemede, jinekolojik kanserlerdeki inflamatuvar yolaklar ve bu yolaklarda etkili sekonder metabolitlerin tedavideki rolü özetlenmektedir. Anahtar kelimeler: Jinekolojik kanserler, yolak, sekonder metabolitler, bitkisel bileşenler, inflamasyon Gynecologic cancers are among the most common cancers in humans and animals. Treatment success depends on several factors including stage at diagnosis, tumor type, origin and metastasis. Currently, surgery, chemotherapy, and radiotherapy are preferred in the treatment of these cancers. However, many anticarcinogenic drugs can cause severe adverse effects and also the expected response to treatment may not be obtained. In recent studies, the importance of the relationship between cancer and inflammation has been emphasized. Therefore, several phytochemicals that exhibit beneficial bioactive effects towards inflammatory pathways were proven to have anticarcinogenic potential for gynecologic cancer therapy. This review summarizes the role of inflammatory pathways in gynecologic cancers and effective secondary metabolites for cancer therapy.

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Phenethyl isothiocyanate suppresses cervical carcinoma metastasis potential and its molecular mechanism

Cited by 12 publications

References 17 publications

Oncogene ATAD2 promotes cell proliferation, invasion and migration in cervical cancer

Oncogene ATAD2 promotes cell proliferation, invasion and migration in cervical cancer

Inhibition of autophagy potentiates the anti‐metastasis effect of phenethyl isothiocyanate through JAK2/STAT3 pathway in lung cancer cells

The Role of Secondary Metabolites on Gynecologic Cancer Therapy: Some Pathways and Mechanisms

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