Pushkal Sinduvadi Ramesh1, Sharanya Raja2, Shwethambari Harave Udayakumar2, Shruthi Chandrashekar2, Suma M Nataraj1, Devananda Devegowda3. 1. Centre of Excellence in Molecular Biology and Regenerative Medicine (DST-FIST Sponsored), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, 570015, India. 2. Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, 570015, India. 3. Centre of Excellence in Molecular Biology and Regenerative Medicine (DST-FIST Sponsored), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, 570015, India. devanandd@jssuni.edu.in.
Abstract
BACKGROUND: Cervical cancers are usually treatable if detected in early stages by a combination of therapies. However, the prognosis of cervical cancer patients with metastasis remains unfavorable due to the fact that most of the cervical carcinomas are either resistant to anticancer drugs or show signs of relapse after initial treatment. Therefore, it is important to control the chemoresistance as it is the key to develop effective treatment options for cervical cancer. OBJECTIVE: The current study aimed at evaluating the differential responses of cervical cancer cells to anti-cancer drugs and assessed whether the differences in the expression profiles of antioxidant genes regulated by nuclear factor erythroid-2-related factor 2 (NRF2), led to the variations in the sensitivities of the cancer cells to treatment. METHODOLOGY: Three cervical cancer cell lines were investigated for their differences in NRF2 pathway by measuring the gene expression and enzyme activity. The differences in the sensitivity to anti-cancer drugs and variation in ROS profile was also evaluated. The addition of exogenous drugs to manipulate the intracellular ROS and its effect on NRF2 pathway genes was also investigated. RESULTS: HeLa and SiHa cells were more sensitive to cisplatin and oxaliplatin treatment than C33A cells. HeLa and SiHa cells had significantly lower NRF2 gene levels, NQO1 enzyme activity and basal GSH levels than C33A cells. Levels of ROS induced were higher in HeLa than C33A cells. CONCLUSION: Overall, the differences in the cellular levels of antioxidant regulatory genes led to the differential response of cervical cancer cells to anti-cancer drugs.
BACKGROUND: Cervical cancers are usually treatable if detected in early stages by a combination of therapies. However, the prognosis of cervical cancer patients with metastasis remains unfavorable due to the fact that most of the cervical carcinomas are either resistant to anticancer drugs or show signs of relapse after initial treatment. Therefore, it is important to control the chemoresistance as it is the key to develop effective treatment options for cervical cancer. OBJECTIVE: The current study aimed at evaluating the differential responses of cervical cancer cells to anti-cancer drugs and assessed whether the differences in the expression profiles of antioxidant genes regulated by nuclear factor erythroid-2-related factor 2 (NRF2), led to the variations in the sensitivities of the cancer cells to treatment. METHODOLOGY: Three cervical cancer cell lines were investigated for their differences in NRF2 pathway by measuring the gene expression and enzyme activity. The differences in the sensitivity to anti-cancer drugs and variation in ROS profile was also evaluated. The addition of exogenous drugs to manipulate the intracellular ROS and its effect on NRF2 pathway genes was also investigated. RESULTS: HeLa and SiHa cells were more sensitive to cisplatin and oxaliplatin treatment than C33A cells. HeLa and SiHa cells had significantly lower NRF2 gene levels, NQO1 enzyme activity and basal GSH levels than C33A cells. Levels of ROS induced were higher in HeLa than C33A cells. CONCLUSION: Overall, the differences in the cellular levels of antioxidant regulatory genes led to the differential response of cervical cancer cells to anti-cancer drugs.
Authors: Catherine de Martel; Damien Georges; Freddie Bray; Jacques Ferlay; Gary M Clifford Journal: Lancet Glob Health Date: 2019-12-17 Impact factor: 26.763
Authors: Marc Arbyn; Elisabete Weiderpass; Laia Bruni; Silvia de Sanjosé; Mona Saraiya; Jacques Ferlay; Freddie Bray Journal: Lancet Glob Health Date: 2019-12-04 Impact factor: 26.763