Cantharidin induces G2/M phase arrest and apoptosis in human gastric cancer SGC-7901 and BGC-823 cells

Zhang, Chenjing; Chen, Zhongting; Zhou, Xinglu; Xu, Wen; Wang, Gang; Tang, Xiaoxiao; Luo, Laisheng; Tu, Jiangfeng; Zhu, Yimiao; Hu, Wen; Xu, Xin; Pan, Wensheng

doi:10.3892/ol.2014.2611

Cited by 33 publications

(28 citation statements)

References 32 publications

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“…Previous studies have reported that CTD efficiently inhibited proliferation and induced apoptosis in various cancer cells, including oral squamous cell carcinoma, renal carcinoma and gastric cancer cells (18)(19)(20). The results of the present study also demonstrated that CTD inhibited A549 cell proliferation and migration, which is consistent with the results of previous studies (18)(19)(20).…”

Section: Discussionsupporting

confidence: 93%

“…The results of the present study also demonstrated that CTD inhibited A549 cell proliferation and migration, which is consistent with the results of previous studies (18)(19)(20). The combined results of these studies provide evidence that CTD is a promising therapeutic candidate for the treatment of NSCLC.…”

Section: Discussionsupporting

confidence: 92%

“…A number of studies have reported that CTD exerted an inhibitory effect on cell proliferation by inducing apoptosis in a variety of tumor cells, including gastric, colorectal and pancreatic cancer cell lines (20)(21)(22). The results of the present study also demonstrated that CTD had a similar effect in promoting the apoptosis of NSCLC cells, by detecting levels of apoptotic markers, including anti-apoptosis protein Bcl-2 and pro-apoptosis proteins like Bax and active caspase-3.…”

Section: Discussionsupporting

confidence: 76%

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Cantharidin suppresses cell growth and migration, and activates autophagy in human non-small cell lung cancer cells

Liu

et al. 2018

Oncol Lett

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Abstract. Cantharidin (CTD), a component of Mylabris (blister beetle), is a traditional Chinese medicine that exerts an anticancer effect in multiple types of cancer cells. The aim of the present study was to investigate whether CTD exhibited anti-metastatic and inhibitory cell proliferation effects against human non-small cell lung cancer (NSCLC) A549 cells, and the possible underlying mechanism by which this occurs. The results of the present study demonstrated that CTD arrested proliferation, suppressed invasion and migration and induced apoptosis in A549 cells in vitro. Alterations of apoptosis-associated protein levels, including B-cell lymphoma-2 (Bcl-2), Bcl-associated X (Bax) and active caspase-3, were detected. Furthermore, the present study demonstrated that CTD activated autophagy through downregulation of p62 expression and upregulation of microtubule-associated proteins 1A/1B light chain 3B and Beclin-1 expression. Additionally, western blot analysis identified that CTD inhibited the phosphatidylinositol 3-kinase (PI3K)/RAC serine/threonine protein kinase (Akt)/mechanistic target of rapamycin (mTOR) signaling pathway in NSCLC, demonstrating that the levels of phosphorylated (p-)Akt, p-mTOR, phosphorylated ribosomal p70S6 protein kinase (p-p70-S6K) and cyclin D1 were significantly decreased following treatment with CTD. In conclusion, the results of the present study indicated that CTD impeded cell growth and migration by inhibiting PI3K/Akt/mTOR signaling in NSCLC, and promoted autophagy and apoptosis. CTD exhibited anticancer activity against NSCLC in vitro, revealing it as a potential candidate for the treatment of NSCLC.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 76%

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Cantharidin suppresses cell growth and migration, and activates autophagy in human non-small cell lung cancer cells

Liu

et al. 2018

Oncol Lett

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“…Cantharidin (CTD) is a type of terpenoid extracted from the traditional Chinese medicine mylabris ( blister beetle ). CTD and its demethylated analogue, norcantharidin (NCTD), were reported to induce G2/M cell cycle arrest and apoptosis in many human solid tumor cells such as hepatocellular carcinoma, pancreatic cancer, prostate cancer, gastric cancer, colon cancer, bladder carcinoma, breast cancer, oral carcinoma, esophageal carcinoma, and melanoma . In contrast to solid tumor cells, the anti‐leukemic effects of CTD and NCTD were also documented .…”

Section: Introductionmentioning

confidence: 99%

Cantharidic acid induces apoptosis of human leukemic HL‐60 cells via c‐Jun N‐terminal kinase‐regulated caspase‐8/‐9/‐3 activation pathway

Wang

Chow

Chien

et al. 2018

Environmental Toxicology

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Cantharidin, a natural toxin from blister beetles, has shown potent anticancer activities on many solid tumor cells. Recently, cantharidin and its analogue, norcantharidin, were also shown to suppress nonsolid tumors such as chronic myeloid leukemia, acute myeloid leukemia (AML), and leukemic stem cells. However, there is no available information to address the effects of cantharidic acid (CAC), a hydrolysis product of cantharidin, on human AML cells. The present study showed that CAC, at a range of concentrations (0-20 μM), concentration-dependently inhibited cell proliferation in the HL-60 AML cell line. Western blot and flow cytometric assays demonstrated that CAC induced several features of apoptosis such as sub G1-phase cell increase, phosphatidylserine (PS) externalization, and significantly activated proapoptotic signaling including caspase-8, -9, and -3 activation and poly(ADP-ribose) polymerase (PARP) cleavage in HL-60 AML cells. Moreover, treatment of HL-60 cells with CAC induced concentration- and time- dependent activation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK). Only JNK-, but not p38 MAPK-specific inhibitor can reverse the CAC-induced activation of the caspase-8, -9, and -3. We concluded that CAC can induce apoptosis in human leukemic HL-60 cells via a caspases-dependent pathway, and that the apoptosis-inducing effect of CAC can be regulated by JNK activation signaling.

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“…Normal cells will cycle through checkpoints signaling pathways to ensure cells have time to repair damaged DNA (Orren et al, 1997). There have been earlier reports of CTD inducing apoptotic cell death in different human cancer cell lines such as colorectal carcinoma cells (Peng et al, 2001), hepatoma cells (Chen et al, 2002), bladder carcinoma cells (Huan et al, 2006), multiple myeloma cells (Sagawa et al, 2008) and lung cancer cells (Hisa et al, 2014b) and gastric cancer cells (Zhang et al, 2014). It was also reported that CTD inhibited cell migration and invasion of human bladder carcinoma cells (Huang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Anticancer effects of cantharidin in A431 human skin cancer (Epidermoid carcinoma) cells in vitro and in vivo

Fan

et al. 2016

Environ. Toxicol.

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Cantharidin (CTD), a potential anticancer agent of Traditional Chinese Medicine has cytotxic effects in different human cancer cell lines. The cytotoxic effects of CTD on A431 human skin cancer (epidermoid carcinoma) cells in vitro and in A431 cell xenograft mouse model were examined. In vitro, A431 human skin cell were treated with CTD for 24 and 48 h. Cell phase distribution, ROS production, Ca release, Caspase activity and the level of apoptosis associated proteins were measured. In vivo, A431 cell xenograft mouse model were examined. CTD-induced cell morphological changes and decreased percentage of viable A431 cells via G0/G1 phase arrest and induced apoptosis. CTD-induced G0/G1 phase arrest through the reduction of protein levels of cyclin E, CDK6, and cyclin D in A431 cells. CTD-induced cell apoptosis of A431 cells also was confirm by DNA gel electrophoresis showed CTD-induced DNA fragmentation. CTD reduced the mitochondrial membrane potential and stimulated release of cytochrome c, AIF and Endo G in A431 cells. Flow cytometry demonstrated that CTD increased activity of caspase-8, -9 and -3. However, when cells were pretreated with specific caspase inhibitors activity was reduced and cell viability increased. CTD increased protein levels of death receptors such as DR4, DR5, TRAIL and levels of the active form of caspase-8, -9 and -3 in A431 cells. AIF and Endo G proteins levels were also enhanced by CTD. In vivo studies showed that CTD significantly inhibited A431 cell xenograft tumors in mice. Taken together, these in vitro and in vivo results provide insight into the mechanisms of CTD on cell growth and tumor production. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 723-738, 2017.

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Cantharidin induces G2/M phase arrest and apoptosis in human gastric cancer SGC-7901 and BGC-823 cells

Cited by 33 publications

References 32 publications

Cantharidin suppresses cell growth and migration, and activates autophagy in human non-small cell lung cancer cells

Cantharidin suppresses cell growth and migration, and activates autophagy in human non-small cell lung cancer cells

Cantharidic acid induces apoptosis of human leukemic HL‐60 cells via c‐Jun N‐terminal kinase‐regulated caspase‐8/‐9/‐3 activation pathway

Anticancer effects of cantharidin in A431 human skin cancer (Epidermoid carcinoma) cells in vitro and in vivo

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