Adiponectin induces growth inhibition and apoptosis in cervical cancer HeLa cells

Abstract

Obesity is a known risk factor for postmenopausal cervical cancer. In human, plasma adiponectin (ADPN) levels are inversely associated with obesity. ADPN may influence the pathogenesis of cervical cancer. In this paper, the effects of ADPN on the proliferation of the cervical cancer HeLa cells and its underlying mechanism were studied. We discovered that two ADPN receptors were expressed in HeLa cells and ADPN inhibited the proliferation of HeLa cells. Western-blotting showed that ADPN activated AMP kinase in HeLa cells. Reverse transcriptase-polymerase chain reaction revealed ADPN down-regulated the expression of cell cycle regulators cyclin D1 and c-myc, and induced the expression of p21 WAF1/CIP1 and p53. These results indicate that ADPN inhibits proliferation and induces apoptosis of HeLa cells by altering the expression of cell cycle regulators.

The Emerging Role of Adiponectin in Female Malignancies

“…Although some evidences suggest that low circulating adiponectin levels related to obesity conditions may be linked to cervical malignancy, nevertheless few studies describe the molecular mechanisms though which adiponectin influences cervical cancer growth [7,92]. Noteworthy in HeLa cells, AdipoR2 mRNA expression was higher than AdipoR1, which was significantly increased in adiponectin-treated cells (10µg/mL) [93]. Xie et al reported that low adiponectin levels inhibited the proliferation of HeLa cells, as evidenced by a significant increase in the cell population in G0/G1 phase, concomitant with a reduction of cell number in S and G2/M phases.…”

“…Xie et al reported that low adiponectin levels inhibited the proliferation of HeLa cells, as evidenced by a significant increase in the cell population in G0/G1 phase, concomitant with a reduction of cell number in S and G2/M phases. Moreover, a down-regulation of cell cycle regulators has been reported, such as cyclin D1 and c-myc, and an activation of apoptosis, mediated by the enhanced expression of p21, p53 and Bax and the reduced level of Bcl-2 [93] (Figure 2).…”

Adipocytokines: Are they the Theory of Everything?

“…Xie et al reported that low adiponectin levels inhibited the proliferation of malignant cells of the cervix, inhibited proto-oncogenes e.g. c-myc, and Bcl-2 and activated apoptosis through enhancing the expression of p53 [37], the same effect was observed with endometrial cancer [38].…”

“…Adiponectin role is the attenuation of the excessive inflammatory response in the wall of the blood vessels of the placenta through inhibition of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling (it is a protein complex that controls transcription of deoxyribonucleic acid (DNA) and cytokine production), decreasing CRP (C-reactive protein) and increasing nitric oxide [42] via activating endothelial nitric oxide synthase and inhibition of superoxide in endothelial cells [43]. Besides, adiponectin mediated the process of trophoblast invasion by modulation of MMP/TIMP (matrix metalloproteinase to tissue inhibitor of metalloproteinase) balance (this is a ratio between active extracellular [11][12][13], hyperlipidemia [22], diabetic kidney disease [30], polycystic ovary [32], ovarian cancer, gestational diabetes [39], systemic sclerosis [74], breast cancer [98], lung cancer [99], colon cancer [100], thyroid cancer [106], prostate cancer [108,109], glioblastoma [113], AIS [129], Duchene Muscular Dystrophy [132], pulmonary hypertension [149], obstructive sleep apnea [151], atherosclerosis [11], hypertension [158], preeclampsia [41][42][43][44], COVID-19 [164] Cervical & endometrial cancer [37,38], joint inflammation [64], bone erosion in rheumatoid arthritis [65], SLE with renal involvement [87] Adipsin Systemic sclerosis with PAH [83], SLE with renal involvement [ Insulin resistance &diabetes [11,…”

Visceral Obesity and Its Shared Role in Cancer and Cardiovascular Disease: A Scoping Review of the Pathophysiology and Pharmacological Treatments

“…It stimulates receptor-mediated signaling pathways and induces apoptosis. In an experimental study on HeLa cells by Xie et al [40], it was observed that low adiponectin levels resulted in a significant increase in cell population in G0/G1 phase, concomitant with a reduction of cell number in S and G2/M phases which proves the inhibition of proliferation by adiponectin. In addition, they observed that adiponectin inhibited proliferation by downregulating cell cycle regulators such as cyclin D1 and c-myc and also activated apoptosis by inducing the expression of p21, p53 and Bax and the reduced level of Bcl-2 [41].…”