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Cancer is one of the leading causes of death in the world. The methods of cancer treatment vary according to its stage and prevalence. Cancer treatment may lead to the emergence of several complications, including side effects from cancer treatment; unusual responses from the immune system to cancer; and cancer relapse. In recent years, scientists have investigated the ability of medicinal plants to treat many diseases. Graviola fruit is one of the plants that affect many diseases, especially cancer.
The aim of this work was to explore if Graviola can reduce the effective dose of cisplatin. This aim was achieved through many steps.
1. Choosing the suitable cell lines.
2. Treating these cell lines with cisplatin.
3. Simultaneous treating cell lines with cisplatin and Graviola.
4. Evaluating the ability of Graviola on reducing the undesirable genotoxic activity of cisplatin.
5. Estimating the effect of Graviola on oxidative stress as MDA and antioxidant parameters (CAT, GSH, and SOD) parameters.
6. Evaluating the influence of Graviola on cell cycle and gene expression of some apoptotic genes (Bax, capsase3, p53), the anti-apoptotic Bcl2 gene, and multi drag resistance genes (MDR1, MAPK1).
The human hepatocellular carcinoma cell line HepG2, colon cancer cell line Caco2, breast cancer cell line MCF7, pancreatic cancer cell line PANC1 were utilized in the present work. All the four cell lines were obtained from the VACSERA (Cairo-Egypt).
Each cell line was divided into four groups as follow:
group 1: Untreated cells (HepG2, Caco2, MCF7, or PANC1)
group 2: Treated with Graviola leave extract (GLE) at a concentration equal its IC50 value (71.66, 82.76, 108.4, and 98.62 μg /ml for MCF7, HepG2, CaCo2, and PCNA1 respectively)
group 3: Treated with cisplatin (CIS) at a concentration equal its IC50 value (8.468, 2.32, 14.3, and 16.65 μg /ml for MCF7, HepG2, CaCo2, and PCNA1 respectively)
group 4: Treated with GLE at a concentration equal its IC50 value (71.66, 82.76, 108.4, and 98.62 μg /ml for MCF7, HepG2, CaCo2, and PCNA1 respectively), then after 2 hour treated with cisplatin at a concentration equal its IC50 value (8.468, 2.32, 14.3, and 16.65 μg /ml for MCF7, HepG2, CaCo2, and PCNA1 respectively)
After treatment, all cell lines were incubated for 24 hours.
VI.1. The obtained results were summarized as follow:
• Combined treatment of GLE plus CIS caused a significant (P ≤ 0.05) higher cytotoxic effect in all the examined cell lines than single-drug treatment.
• GLE pre-treatment improved CIS-induced cytotoxic effect on the four cancer cell lines.
• GLE pre-treatment increased CIS-triggered apoptosis in the examined cancer cells as revealed by the higher expression levels of the three apoptotic genes and the lower expression level of the Bcl2 gene.
• The combined treated group showed lower expression of MDR1 and MAPK1 mRNA levels.
• G0/G1 arrest induced by CIS was shifted to the G2/M phase in the four cell lines. Among the four cell lines, PANC1 showed the highest cell numbers arrested in the G2/M phase following treatment with GLE alone or combined with CIS.
• GLE alone treatment arrested both HepG2 and PANC1 cell lines in the S phase. Moreover, combined treatment of GLE with CIS arrested all examined cancer cell lines in the S phase.
• We assessed whether GLE, which contains many natural antioxidants, can change CIS-induced oxidative stress. Notably, no significant (P ≤ 0.05) changes were noticed in the MDA level or activities of antioxidant enzymes (SOD, CAT, GPX) between the CIS group and the combined treatment group.