Antitumor Activity of Methanolic Fractions Extracted From the Aerial Part of Algerian Hyoscyamus albus and apoptotic cell Aspect Visualization

Neocryptolepine (5-methyl-5H-indolo[2,3-b] quinoline) analogs were synthesized and evaluated in vitro and in vivo for their effect versus Ehrlich ascites carcinoma (EAC). The analogs showed stronger cytotoxic activity against EAC cells than the reference drug. The in vivo evaluation of the target compounds against EAC-induced solid tumor in the female albino Swiss mice revealed a remarkable decrease in the tumor volume (TV) and hepatic lipid peroxidation. A noticeable increase of both superoxide dismutase (SOD) and catalase (CAT) levels was reported (p < 0.001), which set-forth proof of their antioxidant effect. In addition, the in vitro antioxidant activity of the neocryptolepine analogs was screened out using the DPPH method and showed promising activities activity. The histopathological investigations affirmed that the tested analogs have a remarkable curative effect on solid tumors with minimal side-effect on the liver. The study also includes illustrated mechanism of the antitumor activity at the cell level by flow cytometry. The cell cycle analysis showed that the neocryptolepine analogs extensively increase the aggregation of tumor cells in three phases of the cell cycle (G0/G1, S and G2/M) with the emergence of a hypo-diploid DNA content peak (sub-G1) in the cell cycle experiments, which is a clear-cut for the apoptotic cell population. Furthermore, the immunological study manifested a significant elevation in splenic lymphocyte count (p < 0.001) with the elevation of the responsiveness of lymphocytes to phytohemagglutinin (PHA). These results indicate that these naturally-based neocryptolepine alkaloids exhibit marked antitumor activity in vivo and represent an important lead in the development of natural-based anticancer drugs.

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Antitumor activity via apoptotic cell death pathway of water soluble copper(II) complexes: effect of the diamino unit on selectivity against lung cancer NCI-H460 cell line

BioMetals ◽

10.1007/s10534-021-00302-3 ◽

2021 ◽

Author(s):

Wagner da S. Terra ◽

Érika S. Bull ◽

Samila R. Morcelli ◽

Rafaela R. Moreira ◽

Leide Laura F. Maciel ◽

...

Keyword(s):

Lung Cancer ◽

Cell Death ◽

Antitumor Activity ◽

Cell Line ◽

Apoptotic Cell ◽

Apoptotic Cell Death ◽

Water Soluble ◽

Cell Death Pathway ◽

H460 Cell

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Phase Ib/II trial of tisotumab vedotin (TV) ± bevacizumab (BEV), pembrolizumab (PEM), or carboplatin (CBP) in recurrent or metastatic cervical cancer (innovaTV 205/ENGOT-cx8/GOG-3024).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.tps6095 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. TPS6095-TPS6095

Author(s):

Ignace Vergote ◽

Nicole Concin ◽

Mansoor Raza Mirza ◽

Camilla Mondrup Andreassen ◽

Domenica Lorusso ◽

...

Keyword(s):

Cervical Cancer ◽

Antitumor Activity ◽

Phase Ii ◽

Apoptotic Cell ◽

Standard Of Care ◽

Fixed Dose ◽

Antibody Drug Conjugate ◽

Open Label ◽

Phase Ib ◽

Previously Treated

TPS6095 Background: Patients (pts) with recurrent/metastatic cervical cancer (r/mCC) receive paclitaxel/platinum or paclitaxel/topotecan ± BEV as first-line standard-of-care therapy. Tissue factor (TF) expression has been associated with poor prognosis in solid tumors, and TF is highly expressed in r/mCC. TV is an investigational antibody-drug conjugate composed of a fully human, TF-directed monoclonal antibody covalently attached to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. Upon internalization, MMAE is released resulting in cell cycle arrest and apoptotic cell death. In pts with previously treated r/mCC, TV monotherapy (IV 2.0 mg/kg Q3W) demonstrated a manageable safety profile and encouraging antitumor activity (investigator-assessed confirmed ORR, 24%; median DOR, 4.2 mo) [Hong DS et al. Clin Cancer Res. 2019. doi: 10.1158/1078-0432.CCR-19-2962]. The preliminary safety and efficacy data for TV monotherapy suggest a positive benefit/risk profile and warrant further investigation of TV in combination with therapies commonly administered to pts with r/mCC. The global, open-label, phase Ib/II trial innovaTV 205/ENGOT-cx8/GOG-3024 (NCT03786081) evaluates the safety and antitumor activity of TV monotherapy and TV in combination with BEV, PEM, or CBP in pts with untreated or previously treated r/mCC. This abstract presents the new TV monotherapy weekly dosing schedule. Results from this study will inform the further clinical development of TV in the treatment of r/mCC. Methods: Approximately 170 adult pts with recurrent or stage IVB squamous, adenosquamous, or adenocarcinoma of the cervix; measurable disease; and ECOG PS 0-1 will be enrolled. The phase I part of the study will consist of 3 dose-escalation arms for identification of the recommended phase II dose (RP2D) of TV administered Q3W with BEV, PEM, or CBP. In this part, previously treated pts will receive escalating doses of TV (IV Q3W) in combination with escalating doses of BEV (IV Q3W), a fixed dose of PEM (IV Q3W), or a fixed dose of CBP (IV Q3W). The phase II part will include 4 expansion arms. In this phase, pts who have not received prior systemic therapy for r/mCC will receive 1) TV RP2D + PEM or 2) TV RP2D + CBP; pts who received 1-2 prior treatments for r/mCC will receive 3) TV RP2D + PEM or 4) TV monotherapy with weekly dosing (IV 3Q4W). The primary endpoint of phase II is ORR by RECIST v1.1. Secondary endpoints include DOR, time to response, PFS, OS, and safety. Clinical trial information: NCT03786081.

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