Identification of anti-cancer potential of doxazocin: Loading into chitosan based biodegradable hydrogels for on-site delivery to treat cervical cancer

Background: Persistent infection with the high-risk of human papillomavirus (HR-HPVs) is the primary etiological factor of cervical cancer; HR-HPVs express oncoproteins E6 and E7, both of which play key roles in the progression of cervical carcinogenesis. Zinc Finger Nucleases (ZFNs) targeting HPV E7 induce specific shear of the E7 gene, weakening the malignant biological effects, hence showing great potential for clinical transformation. Objective: Our aim was to develop a new comprehensive therapy for better clinical application of ZFNs. We here explored the anti-cancer efficiency of HPV targeted ZFNs combined with a platinum-based antineoplastic drug Cisplatin (DDP) and an HDAC inhibitor Trichostatin A (TSA). Methods: SiHa and HeLa cells were exposed to different concentrations of DDP and TSA; the appropriate concentrations for the following experiments were screened according to cell apoptosis. Then cells were grouped for combined or separate treatments; apoptosis, cell viability and proliferation ability were measured by flow cytometry detection, CCK-8 assays and colony formation assays. The xenograft experiments were also performed to determine the anti-cancer effects of the combined therapy. In addition, the HPV E7 and RB1 expressions were measured by western blot analysis. Results: Results showed that the combined therapy induced about two times more apoptosis than that of ZFNs alone in SiHa and HeLa cells, and much more inhibition of cell viability than either of the separate treatment. The colony formation ability was inhibited more than 80% by the co-treatment, the protein expression of HPV16/18E7 was down regulated and that of RB1 was elevated. In addition, the xenografts experiment showed a synergistic effect between DDP and TSA together with ZFNs. Conclusion: Our results demonstrated that ZFNs combined with DDP or TSA functioned effectively in cervical cancer cells, and it provided novel ideas for the prevention and treatment of HPV-related cervical malignancies.

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Evaluation of Dimer of Epicatechin from an Endophytic Fungus Curvularia australiensis FC2AP on Acute Toxicity Levels, Anti-Inflammatory and Anti-Cervical Cancer Activity in Animal Models

Molecules ◽

10.3390/molecules26030654 ◽

2021 ◽

Vol 26 (3) ◽

pp. 654

Author(s):

Vellingiri Manon Mani ◽

Arockiam Jeyasundar Parimala Gnana Soundari ◽

Balamuralikrishnan Balasubramanian ◽

Sungkwon Park ◽

Utthapon Issara ◽

...

Keyword(s):

Cervical Cancer ◽

Acute Toxicity ◽

Endophytic Fungus ◽

Lethal Dose ◽

Chemotherapeutic Agents ◽

Cancer Drug ◽

Dependent Manner ◽

Anti Cancer ◽

Albino Mice ◽

Anti Inflammatory

Cervical cancer, as the most frequent cancer in women globally and accounts almost 14% in India. It can be prevented or treated with vaccines, radiation, chemotherapy, and brachytherapy. The chemotherapeutic agents cause adverse post effects by the destruction of the neighboring normal cells or altering the properties of the cells. In order to reduce the severity of the side effects caused by the chemically synthesized therapeutic agents, the current research developed an anti-cancer agent dimer of epicatechin (DoE), a natural bioactive secondary metabolite (BSM) mediated from an endophytic fungus Curvularia australiensis FC2AP. The investigation has initiated with the evaluation of inhibiting the angiogenesis which is a main activity in metastasis, and it was assessed through Hen’s Egg Test on Chorio Allantoic Membrane (HET-CAM) test; the BSM inhibited the growth of blood vessels in the developing chick embryo. Further the DoE was evaluated for its acute toxicity levels in albino mice, whereas the survival dose was found to be 1250 mg/kg and the lethal dose was 1500 mg/kg body weight of albino mice; hematological, biochemical, and histopathological analyses were assessed. The anti-inflammatory responses of the DoE were evaluated in carrageenan induced Wistar rats and the reduction of inflammation occurred in a dose-dependent manner. By fixing the effective dose for anti-inflammation analysis, the DoE was taken for the anti-cervical cancer analysis in benzo (a) pyrene induced female Sprague-Dawley rats for 60 days trial. After the stipulated days, the rats were taken for hematological antioxidants, lipid peroxidation (LPO), member bound enzymes, cervical histopathological and carcinogenic markers analyses. The results specified that the DoE has the capability of reducing the tumor in an efficient way. This is the first report of flavonoid-DoE production from an endophytic fungus C. australiensis has the anticancer potentiality and it can be stated as anti-cancer drug.

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Anti-cancer effects of disulfiram in cervical cancer cell lines via both autophagy and apoptosis

Cell Technologies in Biology and Medicine ◽

10.47056/1814-3490-2021-4-238-245 ◽

2021 ◽

pp. 238-245

Author(s):

W. Zhang ◽

◽

Q. Zhai ◽

M. Li ◽

S. Huang ◽

...

Keyword(s):

Cervical Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Cervical Cancer Cell ◽

Anti Cancer

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Mechanisms and Applications of the Anti-cancer Effect of Pharmacological Ascorbic Acid in Cervical Cancer Cells

Frontiers in Oncology ◽

10.3389/fonc.2020.01483 ◽

2020 ◽

Vol 10 ◽

Author(s):

Tsai-Ming Wu ◽

Shu-Ting Liu ◽

Ssu-Yu Chen ◽

Gunng-Shinng Chen ◽

Chia-Chun Wu ◽

...

Keyword(s):

Cervical Cancer ◽

Ascorbic Acid ◽

Cancer Cells ◽

Anti Cancer ◽

Cervical Cancer Cells

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Anti-Cancer Effect of Kaffir Lime (Citrus Hystrix DC) Leaf Extract in Cervical Cancer and Neuroblastoma Cell Lines

Procedia Chemistry ◽

10.1016/j.proche.2015.03.062 ◽

2015 ◽

Vol 14 ◽

pp. 465-468 ◽

Cited By ~ 14

Author(s):

Woro Anindito Sri Tunjung ◽

Jindrich Cinatl ◽

Martin Michaelis ◽

C. Mark Smales

Keyword(s):

Cervical Cancer ◽

Cell Lines ◽

Leaf Extract ◽

Neuroblastoma Cell ◽

Anti Cancer ◽

Neuroblastoma Cell Lines

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Intracellular delivery of NF-κB small interfering RNA for modulating therapeutic activities of classical anti-cancer drugs in human cervical cancer cells

Drugs and Therapy Studies ◽

10.4081/dts.2013.e7 ◽

2013 ◽

Vol 3 (1) ◽

pp. 7 ◽

Cited By ~ 1

Author(s):

Anthony Stanislaus ◽

Anil Philip Kunnath ◽

Snigdha Tiash ◽

Tahereh Fatemian ◽

Nur Izyani Kamaruzman ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Intracellular Delivery ◽

Cyclin B1 ◽

Carbonate Apatite ◽

Cancer Drugs ◽

Small Interfering Rnas ◽

Strong Electrostatic Interaction ◽

Anti Cancer ◽

Gene Transcripts

Cervical cancer is the second most common cancer and fourth leading cause of cancer-related deaths among women. Advanced stage of the disease is treated with radiation therapy and chemotherapy with poor therapeutic outcome and adverse side effects. NFκB, a well-known transcription factor in the control of immunity and inflammation, has recently emerged as a key regulator of cell survival through induction of antiapoptotic genes. Many human cancers, including cervical carcinoma, constitutively express NF-κB and a blockade in expression of its subunit proteins through targeted knockdown of the gene transcripts with small interfering RNAs (siRNA) could be an attractive approach in order to sensitize the cancer cells towards the widely used anti-cancer drugs. However, the inefficiency of the naked siRNA to cross the plasma membrane and its sensitiveness to nuclease-mediated degradation are the major challenges limiting the siRNA technology in therapeutic intervention. pH-sensitive carbonate apatite has been established as an efficient nano-carrier for intracellular delivery of siRNA, due to its strong electrostatic interaction with the siRNA, the desirable size distribution of the resulting siRNA complex for effective endocytosis and the ability of the endocytosed siRNA to be released from the degradable particles and escape the endosomes, thus leading to the effective knockdown of the target gene of cyclin B1 or ABCB1. Here, we report that carbonate apatite-facilitated delivery of the siRNA targeting NF-κB1 and NF-κB2 gene transcripts in HeLa, a human cervical adenocar- cinoma cell line expressing NF-κB, led to a synergistic effect in enhancement of chemosensitivity to doxorubicin, but apparently not to cisplatin or paclitaxel.

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