Mehdi Rezai1, Ramin Saravani1,2, Saman Sargazi2, Mahdiyeh Moudi3, Mahdieh Jafari Shahroudi2, Roya Saravani4. 1. Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran. 2. Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran. 3. Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran. 4. Department of Chemistry, Iran University of Science and Technology; Tehran, Iran.
Abstract
BACKGROUND: Inappropriate activation of the proto-oncogene LIN28B and inactivation of the p53 tumor suppressor, have been shown to have a critical role in tumorigenesis. Previous research has shown therapeutic potential for the use of herbal plants as an alternative strategy for cancer treatment. Achillae wilhelmsii C. Koch is a plant that has been traditionally used for its medicinal properties. The aim of this study was to investigate the cytotoxic and apoptosis-inducing effect of Achillea wilhelmsii C. Koch hydroalcoholic extract (AWHE) on HeLa cervical cancer cells and its effect on LIN28B and p53 expression. METHODS: The cytotoxic activity of AWHE was evaluated on HeLa cells using a trypan blue exclusion assay. The Annexin V/PI double staining assay was used to evaluate the apoptosis-inducing effect of the extract. The expression of LIN28B and p53 mRNA was measured using the real-time-PCR method. RESULTS: Treatment with AWHE was shown to induce cytotoxicity in both time and concentration-dependent manners (P<0.05). The proposition of HeLa cells undergoing apoptosis increased with increasing concentrations of AWHE (P<0.05). The mRNA levels of p53 increased following 12, 24, and 48 hours of AWHE treatment whereas the mRNA levels of LIN28B were significantly decreased after 4 to 12 hours of AWHE treatment (p<0.05). CONCLUSION: Our findings confirmed the pro-apoptotic function of AWHE on the cervical cancer HeLa cell line. This indicates that targeting the LIN28B signaling cascade may be a promising therapeutic strategy for cervical cancer. Further research is required to understand the therapeutic effects of AWHE in primary human cervical cancer cells and a pre-clinical cervical cancer model.
BACKGROUND: Inappropriate activation of the proto-oncogene LIN28B and inactivation of the p53 tumor suppressor, have been shown to have a critical role in tumorigenesis. Previous research has shown therapeutic potential for the use of herbal plants as an alternative strategy for cancer treatment. Achillae wilhelmsii C. Koch is a plant that has been traditionally used for its medicinal properties. The aim of this study was to investigate the cytotoxic and apoptosis-inducing effect of Achillea wilhelmsii C. Koch hydroalcoholic extract (AWHE) on HeLa cervical cancer cells and its effect on LIN28B and p53 expression. METHODS: The cytotoxic activity of AWHE was evaluated on HeLa cells using a trypan blue exclusion assay. The Annexin V/PI double staining assay was used to evaluate the apoptosis-inducing effect of the extract. The expression of LIN28B and p53 mRNA was measured using the real-time-PCR method. RESULTS: Treatment with AWHE was shown to induce cytotoxicity in both time and concentration-dependent manners (P<0.05). The proposition of HeLa cells undergoing apoptosis increased with increasing concentrations of AWHE (P<0.05). The mRNA levels of p53 increased following 12, 24, and 48 hours of AWHE treatment whereas the mRNA levels of LIN28B were significantly decreased after 4 to 12 hours of AWHE treatment (p<0.05). CONCLUSION: Our findings confirmed the pro-apoptotic function of AWHE on the cervical cancer HeLa cell line. This indicates that targeting the LIN28B signaling cascade may be a promising therapeutic strategy for cervical cancer. Further research is required to understand the therapeutic effects of AWHE in primary human cervical cancer cells and a pre-clinical cervical cancer model.
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