Novel action modality of the diterpenoid anisomelic acid causes depletion of E6 and E7 viral oncoproteins in HPV-transformed cervical carcinoma cells

Paul, Preethy; Rajendran, Senthil Kumar; Peuhu, Emilia; Alshatwi, Ali A.; Akbarsha, Mohammad A.; Hietanen, Sakari; Eriksson, John E.

doi:10.1016/j.bcp.2014.02.011

Cited by 15 publications

(13 citation statements)

References 38 publications

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“…This phenomenon was different from other compounds, e.g. anisomelic acid, which recover the expression level of p53 when E6/E7 degrade 18 . The decreased expression level of p53 after NADA treatment also revealed that NADA-induced apoptosis was p53 independent.…”

Section: Discussioncontrasting

confidence: 66%

“…In recent years, natural compounds have been extensively explored for their potential usage as treatments for cervical cancer via suppressing E6/E7. For example, Tanshinone IIA inhibited E6/E7 at the transcription level and led to the reactivation of the p53-dependent growth inhibition of cervical cancer cells 17 ; Anisomelic acid down-regulated E6/E7 at protein level by proteasome degradation and induced p53-independent mitochondrial apoptosis in Siha cells 18 ; N-benzylcinnamide, purified from Piper submultinerve, promoted human cervical carcinoma CaSki and HeLa cell lines apoptosis by inhibiting E6/E7 expression at mRNA level 19 ; Docosahexaenoic acid caused ROS-dependent-UPS-mediated E6/E7 degradation and the death of HPV-associated cancer cells 20 . Thus, natural compounds which induce E6/E7 degradation could be a remarkable source of anti-cervical cancer agents.…”

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confidence: 99%

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Marine Streptomyces sp. derived antimycin analogues suppress HeLa cells via depletion HPV E6/E7 mediated by ROS-dependent ubiquitin–proteasome system

Zhang

Che

Tan

et al. 2017

Sci Rep

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Four new antimycin alkaloids (1–4) and six related known analogs (5–10) were isolated from the culture of a marine derived Streptomyces sp. THS-55, and their structures were elucidated by extensive spectroscopic analysis. All of the compounds exhibited potent cytotoxicity in vitro against HPV-transformed HeLa cell line. Among them, compounds 6–7 were derived as natural products for the first time, and compound 5 (NADA) showed the highest potency. NADA inhibited the proliferation, arrested cell cycle distribution, and triggered apoptosis in HeLa cancer cells. Our molecular mechanic studies revealed NADA degraded the levels of E6/E7 oncoproteins through ROS-mediated ubiquitin-dependent proteasome system activation. This is the first report that demonstrates antimycin alkaloids analogue induces the degradation of high-risk HPV E6/E7 oncoproteins and finally induces apoptosis in cervical cancer cells. The present work suggested that these analogues could serve as lead compounds for the development of HPV-infected cervical cancer therapeutic agents, as well as research tools for the study of E6/E7 functions.

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Section: Discussioncontrasting

confidence: 66%

mentioning

confidence: 99%

Marine Streptomyces sp. derived antimycin analogues suppress HeLa cells via depletion HPV E6/E7 mediated by ROS-dependent ubiquitin–proteasome system

Zhang

Che

Tan

et al. 2017

Sci Rep

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“…In addition, cdc2 activation depends on the dephosphorylation of Tyr15 by cdc25c. Otherwise, p53 and the p53-responsive gene, p21, can suppress cyclin B1 and cdc2 expression by inhibiting either cdc2 kinase activity or blocking the interaction of cyclin B1-cdc2 complexes with their substrates, leading to G2/M-phase cell cycle arrest (23)(24)(25)(26)(27). Furthermore, the MEK-ERK pathway has crosstalk with p53/p21, and Bax is a key target of the p53 transcription process in aspects of cell apoptosis (26).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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Abstract. Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with high incidence and mortality worldwide. Diallyl disulfide (DADS) is a natural organosulfur compound, isolated from garlic. In this study, MTT assay showed that DADS significantly reduced cell viability in a dose-and timedependent manner in ESCC cells, with lower toxicity in normal liver cells. Cell cycle analysis revealed that DADS made G2/M phase arrest. Molecular analysis suggested that this cell cycle arrest was likely made by the decrease of cyclin B1, cdc2, p-cdc2, cdc25c in concomitance with activation of the p53/p21 pathway. Apoptosis was detected by Annexin V/PI staining. The molecule markers showed that DADS induced apoptosis through activating caspases, altering the Bax/Bcl-2 balance and suppressing the MEK-ERK pathway. Our data indicated that DADS has the potential to be an effective and safe anticancer agent for ESCC therapy in the near future.

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“…S1 †) is a diterpenoid compound isolated from the medicinal plant Anisomeles malabarica 7 , which we have previously shown to be cytotoxic to oral and cervical cancer cells. 8 Recently, we have shown that AA induces apoptosis and cause cell cycle arrest in SiHa cervical cancer cells by specifically down-regulating the viral oncoproteins, E6 and E6, 9,10 which are the main reasons behind cervical carcinogenesis. 10 Targeted delivery of anticancer drugs using nanocarriers is a promising approach to alleviate the drawbacks of conventional cancer therapy, offering the advantages of reduced dosage of drug, and delivering it at the tumor site to avoid sideeffects.…”

Section: Introductionmentioning

confidence: 99%

Targeted delivery of a novel anticancer compound anisomelic acid using chitosan-coated porous silica nanorods for enhancing the apoptotic effect

et al. 2015

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Targeted delivery of a novel anticancer compound anisomelic acid using chitosan-coated porous silica nanorods for enhancing the apoptotic effect, 2015, BIOMATERIALS SCIENCE, (3) Targeted cancer therapies are currently a strong focus in biomedical research. The most common approach is to use nanocarrier-based targeting to specifically deliver conventional anticancer drugs to enhance their therapeutic efficacy, increase bioavailabil ity, and decrease the side-effects on normal cells. A step further towards higher specificity and efficacy would be to employ specific novel drugs along with specific nanocarrier -based targeting. Our recent studies have demonstrated that a plant-derived diterpenoid compound, anisomelic acid (AA), induces apoptosis in cervical cancer cells. In this work, we describe the development of a folic acid (FA)-targeted AA delivery system using chitosan-coated rod-shaped mesoporous silica particles (Chitosan-NR-MSP). The cellular internalization and and uptake enhancement of the FA-Chitosan-NR-MSP towards cancerous folate receptor (FR) -positive (SiHa and HeLa) and/or normal FR-negative (HEK 293) cells were assessed, which indicated that the intracellular uptake of FA-conjugated Chitosan-NR-MSP was more target-specific. Furthermore, the induction of apoptosis by AA-loaded chitosan-coated rod-shaped particles on SiHa cells was studied. By employing caspase activation and PARP cleavage as measure of apoptosis, the FA-particle mediated AA treatment was clearly more effective, significantly enhancing apoptosis in comparison to non-targeted Chitosan-NR-MSP or free AA in SiHa cells, suggesting that the FA-Chitosan-NR-MSPs can be potentially utilized as a drug delivery system for cervical cancer treatment.

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Novel action modality of the diterpenoid anisomelic acid causes depletion of E6 and E7 viral oncoproteins in HPV-transformed cervical carcinoma cells

Cited by 15 publications

References 38 publications

Marine Streptomyces sp. derived antimycin analogues suppress HeLa cells via depletion HPV E6/E7 mediated by ROS-dependent ubiquitin–proteasome system

Marine Streptomyces sp. derived antimycin analogues suppress HeLa cells via depletion HPV E6/E7 mediated by ROS-dependent ubiquitin–proteasome system

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

Targeted delivery of a novel anticancer compound anisomelic acid using chitosan-coated porous silica nanorods for enhancing the apoptotic effect

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