Serum-resistant, reactive oxygen species (ROS)-potentiated gene delivery in cancer cells mediated by fluorinated, diselenide-crosslinked polyplexes

Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.

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ent-Kaurane Diterpenoids from Croton tonkinensis Induce Apoptosis in Colorectal Cancer Cells through the Phosphorylation of JNK Mediated by Reactive Oxygen Species and Dual-Specificity JNK Kinase MKK4

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520614666140127111407 ◽

2014 ◽

Vol 14 (7) ◽

pp. 1051-1061 ◽

Cited By ~ 8

Author(s):

Phuong Thuong ◽

Nguyen Khoi ◽

Saho Ohta ◽

Shinichiro Shiota ◽

Hironori Kanta ◽

...

Keyword(s):

Colorectal Cancer ◽

Reactive Oxygen Species ◽

Cancer Cells ◽

Reactive Oxygen ◽

Oxygen Species ◽

Dual Specificity ◽

Colorectal Cancer Cells

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Photo-Responsive Supramolecular Micelles for Controlled Drug Release and Improved Chemotherapy

International Journal of Molecular Sciences ◽

10.3390/ijms22010154 ◽

2020 ◽

Vol 22 (1) ◽

pp. 154

Author(s):

Fasih Bintang Ilhami ◽

Kai-Chen Peng ◽

Yi-Shiuan Chang ◽

Yihalem Abebe Alemayehu ◽

Hsieh-Chih Tsai ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Drug Release ◽

Visible Light ◽

Cancer Cells ◽

Laser Irradiation ◽

Reactive Oxygen ◽

Controlled Drug Release ◽

Grand Challenge ◽

Supramolecular System ◽

Oxygen Species

Development of stimuli-responsive supramolecular micelles that enable high levels of well-controlled drug release in cancer cells remains a grand challenge. Here, we encapsulated the antitumor drug doxorubicin (DOX) and pro-photosensitizer 5-aminolevulinic acid (5-ALA) within adenine-functionalized supramolecular micelles (A-PPG), in order to achieve effective drug delivery combined with photo-chemotherapy. The resulting DOX/5-ALA-loaded micelles exhibited excellent light and pH-responsive behavior in aqueous solution and high drug-entrapment stability in serum-rich media. A short duration (1–2 min) of laser irradiation with visible light induced the dissociation of the DOX/5-ALA complexes within the micelles, which disrupted micellular stability and resulted in rapid, immediate release of the physically entrapped drug from the micelles. In addition, in vitro assays of cellular reactive oxygen species generation and cellular internalization confirmed the drug-loaded micelles exhibited significantly enhanced cellular uptake after visible light irradiation, and that the light-triggered disassembly of micellar structures rapidly increased the production of reactive oxygen species within the cells. Importantly, flow cytometric analysis demonstrated that laser irradiation of cancer cells incubated with DOX/5-ALA-loaded A-PPG micelles effectively induced apoptotic cell death via endocytosis. Thus, this newly developed supramolecular system may offer a potential route towards improving the efficacy of synergistic chemotherapeutic approaches for cancer.

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