Therapeutic effects of cantharidin analogues without bridging ether oxygen on human hepatocellular carcinoma cells

Yeh, Chao‐Bin; Su, Cheng‐Kuan; Hwang, Jin-Ming; Chou, Ming-Chih

doi:10.1016/j.ejmech.2010.05.053

Cited by 42 publications

(32 citation statements)

References 18 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, because of nephrotoxic and other side effects, norcantharidin (NCTD) was synthesized in an effort to reduce toxicity. Currently, NCTD is widely used in the treatment of tumors (7,15).…”

Section: Discussionmentioning

confidence: 99%

Atg5 siRNA inhibits autophagy and enhances norcantharidin-induced apoptosis in hepatocellular carcinoma

Xiong

Zhang

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Cantharidin is a terpenoid isolated from Chinese blister beetles, and norcantharidin (NCTD) is a demethylated analog of cantharidin. It has been reported that cantharidin and norcantharidin have anticancer activities. Growing evidence suggests that inhibiting autophagy can induce apoptosis in the human hepatoma cell line HepG2. The objective of the present study was to determine whether inhibition of autophagy enhances NCTD-induced apoptosis in HepG2 cells. HepG2 cells were cultured in DMEM containing NCTD. Autophagy was upregulated in the presence of HBSS media supplemented with Ca 2+ and Mg 2+ and 10 mM HEPES and downregulated in the presence of 3-methyladenine (3-MA) and Atg5 siRNA. Autophagy, cell viability, and the expression of apoptotic proteins were assessed in HepG2 cells. Our data showed that cell apoptosis generally increased after norcantharidin treatment in HepG2 cells. Expression of LC3-II, an autophagosome marker, increased when cells were treated with HBSS media. It also increased cell viability. However, in the presence of 3-MA and Atg5 siRNA, autophagy was inhibited, LC3-II expression decreased and cell apoptosis increased. There was increased expression of Bax, cytochrome c, cleaved caspase-3, caspase-9 and PARP and the mitochondrial membrane potential was disrupted. Additionally, increased apoptosis was accompanied by increased reactive oxygen species (ROS) production. NCTD has anticancer activity, and Atg5 siRNA-mediated downregulation of autophagy enhanced its anticancer actions due to ROS generation and activation of the mitochondrial apoptosis pathway. IntroductionLiver cancer is the sixth most frequent cancer and the second leading cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) represents 90% of all primary liver cancers (1-3). The 5-year survival rate for HCC is <30% and the recurrence rate is ~70% (4,5). Current HCC treatments, including surgical resection, liver transplantation, chemotherapy, or immuno-biological cancer therapies, are typically not very effective.Cantharidin is a terpenoid isolated from Chinese blister beetles, and norcantharidin (NCTD) is a demethylated analog of cantharidin that has anticancer activity in breast cancer, lung cancer, leukemia, colon and liver cancer. One possible explanation for the anticancer actions of NCTD is its inhibition of protein phosphatases, through which G0/G1 or G2/M arrest is triggered. Thus, apoptosis is subsequently induced via ROS generation and the mitochondrial pathway (6,7).Autophagy, an important pathophysiological process, is crucial for cell development, differentiation, survival and homeostasis. Additionally, autophagy has an important role in liver cancer. Previous studies have shown that autophagy is induced in liver cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Atg5 siRNA inhibits autophagy and enhances norcantharidin-induced apoptosis in hepatocellular carcinoma

Xiong

Zhang

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…Also, CTD has been used as a medical agent over 2,000 years and there are many applications, including abortifacient, dropsy, aphrodisiac and warts (13). In recent studies, CTD was shown to be able to inhibit cell proliferation in many types of cancer cell lines such as pancreatic cancer, hepatoma, bladder carcinoma and breast cancer (15)(16)(17). CTD can also reduce the activity of protein phosphatase 2A (PP2A) (15) which is likely to suppress tumor proliferation and also used as a target molecule to detect the suppression of tumor (17).…”

Section: Introductionmentioning

confidence: 99%

“…In recent studies, CTD was shown to be able to inhibit cell proliferation in many types of cancer cell lines such as pancreatic cancer, hepatoma, bladder carcinoma and breast cancer (15)(16)(17). CTD can also reduce the activity of protein phosphatase 2A (PP2A) (15) which is likely to suppress tumor proliferation and also used as a target molecule to detect the suppression of tumor (17). Therefore, the purpose of this study was to examine whether CTD might inhibit proliferation and in vitro anticancer mechanisms of apoptosis in human colorectal cancer colo 205 cells.…”

Section: Introductionmentioning

confidence: 99%

Cantharidin induces G2/M phase arrest and apoptosis in human colorectal cancer colo 205 cells through inhibition of CDK1 activity and caspase-dependent signaling pathways

Chen¹

2011

Int J Oncol

View full text Add to dashboard Cite

Abstract. Cantharidin (CTD) is a traditional Chinese medicine and an effective component isolated from blister beetle, and it has been demonstrated to have anticancer, antibiotic, antivirus activities and immune-regulated functions. It has been reported that CTD induces cell cycle arrest and apoptosis in many cancer cell types. However, there are no reports showing that CTD would induce cell cycle arrest and apoptosis in human colorectal cancer colo 205 cells. In this study, we studied colo 205 cells which were treated with CTD and demonstrated its molecular mechanisms in apoptosis. CTD induced growth inhibition, G2/M phase arrest and apoptosis in colo 205 cells. The IC 50 is 20.53 µM in CTD-treated colo 205 cells. DAPI/TUNEL double staining and Annexin V assays were used to confirm the apoptotic cell death in colo 205 cells after CTD exposure. CTD caused G2/M arrest, down-regulated CDK1 activity, decreased Cyclin A, Cyclin B, CDK1 and increased CHK1 and p21 protein levels. Colorimetric assays also indicated that CTD triggered activities of casapse-8, -9 and -3 in colo 205 cells. Moreover, CTD increased ROS production and decreased the level of mitochondrial membrane potential (ΔΨm) in colo 205 cells. Consequently, CTD-induced growth inhibition was significantly attenuated by N-acetylcysteine (NAC, a scavenger). CTD stimulated the protein levels of Fas/CD95, the caspase-3 active form, cytochrome c and Bax, but suppressed the protein levels of pro-caspase-8, pro-caspase-9 and Bcl-2, determined by Western blot analysis. Based on our observations, we suggest that CTD is able to induce G2/M phase arrest and apoptosis in colo 205 cells through inhibition of CDK1 activity and caspase-dependent signaling pathways.

show abstract

“…1 Therefore, scientists have persisted in the search to maximize its potential, and many CTD derivatives and several novel drug-delivery systems have been developed. [10][11][12][13] Non-ionic surfactant vehicles (NSVs), the so-called niosomes, have attracted major attention as a new drugdelivery system in the pharmaceutical field since the late 1980s. As an alternative approach to the conventional l iposomal devices, NSVs are formed by the self-assembly of non-ionic amphiphiles in aqueous media, resulting in closed spheroidal structures.…”

Section: Introductionmentioning

confidence: 99%

Non-ionic surfactant vesicles simultaneously enhance antitumor activity and reduce the toxicity of cantharidin

Han¹,

Wang²,

Liang³

et al. 2013

IJN

View full text Add to dashboard Cite

Objective:The objective of the present study was to prepare cantharidin-entrapped non-ionic surfactant vesicles (CTD-NSVs) and evaluate their potential in enhancing the antitumor activities and reducing CTD's toxicity. Methods and results: CTD-NSVs were prepared by injection method. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry analysis showed that CTD-NSVs could significantly enhance in vitro toxicity against human breast cancer cell line MCF-7 and induce more significant cell-cycle arrest in G0/G1 phase. Moreover, Hoechst 33342 staining implicated that CTD-NSVs induced higher apoptotic rates in MCF-7 cells than free CTD solution. In vivo therapeutic efficacy was investigated in imprinting control region mice bearing mouse sarcoma S 180 . Mice treated with 1.0 mg/kg CTD-NSVs showed the most powerful antitumor activity, with an inhibition rate of 52.76%, which was significantly higher than that of cyclophosphamide (35 mg/kg, 40.23%) and the same concentration of free CTD (1.0 mg/kg, 31.05%). In addition, the acute toxicity and liver toxicity of CTD were also distinctly decreased via encapsulating into NSVs. Conclusion: Our results revealed that NSVs could be a promising delivery system for enhancing the antitumor activity and simultaneously reducing the toxicity of CTD.

show abstract

Therapeutic effects of cantharidin analogues without bridging ether oxygen on human hepatocellular carcinoma cells

Cited by 42 publications

References 18 publications

Atg5 siRNA inhibits autophagy and enhances norcantharidin-induced apoptosis in hepatocellular carcinoma

Atg5 siRNA inhibits autophagy and enhances norcantharidin-induced apoptosis in hepatocellular carcinoma

Cantharidin induces G2/M phase arrest and apoptosis in human colorectal cancer colo 205 cells through inhibition of CDK1 activity and caspase-dependent signaling pathways

Non-ionic surfactant vesicles simultaneously enhance antitumor activity and reduce the toxicity of cantharidin

Contact Info

Product

Resources

About