Curcin C inhibit osteosarcoma cell line U2OS proliferation by ROS induced apoptosis, autophagy and cell cycle arrest through activating JNK signal pathway

Aim: The clinical application of cisplatin is limited by severe side effects associated with high applied doses. The synergistic effect of a combination treatment of a low dose of cisplatin with the natural alkaloid α-solanine on human hepatocellular carcinoma cells was evaluated. Methods: HepG2 cells were exposed to low doses of α-solanine and cisplatin, either independently or in combination. The efficiency of this treatment modality was evaluated by investigating cell growth inhibition, cell cycle arrest, and apoptosis enhancement. Results: α-solanine synergistically potentiated the effect of cisplatin on cell growth inhibition and significantly induced apoptosis. This synergistic effect was mediated by inducing cell cycle arrest at the G2/M phase, enhancing DNA fragmentation and increasing apoptosis through the activation of caspase 3/7 and/or elevating the expression of the death receptors DR4 and DR5. The induced apoptosis from this combination treatment was also mediated by reducing the expression of the anti-apoptotic mediators Bcl-2 and survivin, as well as by modulating the miR-21 expression. Conclusion: Our study provides strong evidence that a combination treatment of low doses of α-solanine and cisplatin exerts a synergistic anticancer effect and provides an effective treatment strategy against hepatocellular carcinoma.

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Anticancer Effect of Amygdalin (Vitamin B-17) on Hepatocellular Carcinoma Cell Line (HepG2) in the Presence and Absence of Zinc

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200120095525 ◽

2020 ◽

Vol 20 (4) ◽

pp. 486-494

Author(s):

Mohamed A. El-Desouky ◽

Abdelgawad A. Fahmi ◽

Ibrahim Y. Abdelkader ◽

Karima M. Nasraldin

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Cycle ◽

Cytochrome C ◽

Cell Cycle Arrest ◽

Cell Line ◽

Hepg2 Cell ◽

Caspase 3 ◽

Vitamin B ◽

Cycle Arrest ◽

Hepg2 Cell Lines

Background: Amygdalin (Vitamin B-17) is a naturally occurring vitamin found in the seeds of the fruits of Prunus Rosacea family including apricot, bitter almond, cherry, and peach. Objective: The purpose of this study was to examine the effect of amygdalin with and without zinc on hepatocellular carcinoma (HepG2) cell line. Methods: MTT assay was used to evaluate the cytotoxicity of amygdalin without zinc, amygdalin + 20μmol zinc, and amygdalin + 800μmol zinc on HepG2 cell lines. The cell cycle distribution assay was determined by flow cytometry. Apoptosis was confirmed by Annexin V-FITC/PI staining assay. Moreover, the pathway of apoptosis was determined by the percentage of change in the mean levels of P53, Bcl2, Bax, cytochrome c, and caspase-3. Results: Amygdalin without zinc showed strong anti-HepG2 activity. Furthermore, HepG2 cell lines treatment with amygdalin + 20μmol zinc and amygdalin + 800μmol zinc showed a highly significant apoptotic effect than the effect of amygdalin without zinc. Amygdalin treatment induced cell cycle arrest at G2/M and increased the levels of P53, Bax, cytochrome c, and caspase-3 significantly, while it decreased the level of anti-apoptotic Bcl2. Conclusion: Amygdalin is a natural anti-cancer agent, which can be used for the treatment of hepatocellular carcinoma. It promotes apoptosis via the intrinsic cell death pathway (the mitochondria-initiated pathway) and cell cycle arrest at G/M. The potency of amygdalin in HepG2 treatment increased significantly by the addition of zinc.

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