In-vitro anti-cancer activity of shape controlled silver nanoparticles (AgNPs) in various organ specific cell lines

104 Background: Castrate resistant prostate cancer (CRPC) continues to be sensitive to anti-androgen therapy as evidenced by the recent successes of abiraterone acetate (AA) and enzalutamide (ENZ). VT-464 is a novel, non-steroidal, small molecule CYP17A1 inhibitor with selectivity for the lyase activity of this dual enzyme. The objective of this study was to evaluate the anti-cancer activity of VT-464 compared to AA in CRPC in vitro models that are ENZ-responsive and ENZ-resistant and in an ENZ-resistant xenograft model. Methods: In vitro studies used the human CRPC, C4-2, and ENZ-resistant cell lines, MR49C and MR49F cells, in androgen-free media. AR transcriptional activity was assessed by probasin luciferase. AR-related and steroidogenesis pathways were assessed by western blot and/or qRT-PCR. A MR49F xenograft model in castrate mice compared oral VT-464 treatment to vehicle and AA. Steroid concentrations were measured using LC-MS chromatography. Results: VT-464 demonstrated a greater decrease in AR transactivation compared to AA in C4-2 and both ENZ-resistant cell lines. A greater decrease in AR-dependent gene transcription occurred with VT-464 treatment compared to AA in all cell lines. Prostate-specific antigen (PSA) protein levels in vitro were also lower with VT-464. Gene transcripts StAR, CYP17A1, HSD17B3 and SRD5A1 increased following treatment with VT-464 both in vitro and in vivo. A greater increase was seen with VT-464 treatment compared to AA. In vivo results demonstrated greater tumor growth inhibition and decreased serum PSA levels in mice treated with oral VT-464 compared to AA. Steroid analysis revealed lower testosterone (T) and dihydrotestosterone (DHT) concentrations in C4-2 cells with VT-464 treatment compared to AA. In vivo, the intra-tumoral DHT and T levels were significantly lower in response to VT-464 or AA compared to vehicle, with the greatest decrease seen with VT-464. Conclusions: The selective CYP17 inhibitor VT-464 demonstrated anti-cancer activity in pre-clinical models of CRPC, lowering intratumoral T and DHT concentrations significantly in castrate mice. These results suggest greater androgen suppression and inhibition of AR axis signaling by VT-464 than by AA.

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Screening of Amodiaquine for its in vitro Anti-cancer Activity on Breast Cancer Cell Lines- a Case Study for Drug Reprofiling

Pan African Journal of Life Sciences ◽

10.36108/pajols/1202.50.0240 ◽

2021 ◽

Vol 5 (2) ◽

pp. 263-273

Author(s):

Kehinde S. Salako

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Flow Cytometry Analysis ◽

Anti Cancer ◽

Cancer Activity

Background: Cancer is one of the foremost contributors to global disease bur den and constantly requires new therapeutic options. The development of new drugs has failed to keep up with its incidence. Hence, drug reprofiling strategies are emerging as novel therapeutic options. The study aimed to evaluate the anti-cancer activity of amodiaquine (anti-malarial drug) using a combination of murine and human breast cancer cell lines Methods: Amodiaquine was authenticated by ultra-violet spectrophotometry, high- performance liquid chromatography and 1D nuclear magnetic resonance. In vitro cytotoxicity of amodiaquine was evaluated against three breast cancer cell lines. MDA-MB-453, 4T1 and MDA-MB-231 cells were incubated with the drug at different concentrations (0.78, 1.56, 3.13, 6.25, 12.50, 25.00, 50.00, 100.00 μM) for 72 h, after which cell viability testing was conducted using the cell counting kit-8 assay. Negative control in which no drug was added to the cells was also evaluated. The flow cytometry analysis of MDA-MB-231 cells when treated with amodiaquine was also evaluated by a flow cytometer using annexin V/propidium iodide staining assay. Results: Cell viability studies showed that the IC50 values of amodiaquine on MDA-MB-453, 4T1, and MDAMB-231 cells were 6.48 ± 1.12, 10.50 ± 1.17, and 19.23 ± 1.16 μM, respectively. The flow cytometry analysis of MDA-MB-231 cancer cells treated with amodiaquine showed cancer cell death by necrosis. Conclusion: This study has shown that amodiaquine may be potentially reprofiled as an anti-cancer agent in managing androgen receptor-positive / HER-2 positive and triple-negative breast cancer types. An additional probable mechanism of action of anti-cancer activity of amodiaquine was found to be necrosis .

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