Anti-drug resistance, anti-inflammation, and anti-proliferation activities mediated by melatonin in doxorubicin-resistant hepatocellular carcinoma: in vitro investigations

• DOI: 10.1007/s00210-023-02385-w
• Publication Date: 2023-01-18T11:02:57Z
• Authors: Ahmed R. Hamed; Shaymaa M. M. Yahya; Heba K. Nabih
• Keywords: ABCC1

Abstract Hepatocellular carcinoma (HCC) is the major life-threatening primary liver malignancy in both sexes all over world. Unfortunately, majority of patients are diagnosed at later stages because HCC does not elicit obvious symptoms during its early incidence. Consequently, most individuals escape first-line treatments and treated with chemotherapy. Regrettably, therapeutic outcomes for those usually poor development multidrug resistance phenomena. Furthermore, anti-HCC therapies cause severe undesired side effects that notably interfere life quality such patients. Accordingly, there an important need to search alternative drug or adjuvant which more efficient safe even minimal treatment. Melatonin was recently reported exert intrinsic antitumor activity different cancers. However, regulatory pathways underlying melatonin poorly understood resistant cells. a limited number studies have addressed role cells doxorubicin In this study, we investigated doxorubicin-resistant HepG2 explored pivotal targets these effects. To achieve our aim, MTT assay used calculate 50% inhibitory concentration evaluate antiproliferative effect on Additionally, qRT-PCR quantify genes having phenotype (ABCB1, ABCC1, ABCC2, ABCC3, ABCC4, ABCC5, ABCG2); apoptosis (caspases-3, -7, Bcl2, Bax, p53); anti-oxidation (NRF2); expression receptors (MT1, MT2, MT3); besides, programmed death receptor PD-1 gene. The active form caspase-3 enzyme estimated by ELISA. A human inflammatory antibody membrane array employed forty factors expressed We observed inhibited proliferation dose-dependent manner after 24-h incubation time calculated IC 50 greater than 10 mM (13.4 mM), levels involved response ABCG2) were downregulated. Also, caspase-3, Caspase-7, NRF2, p53 higher as compared control (DMSO-treated cells). An confirmed Moreover, anti-inflammatory detected through fold change reduced various mediators inflammation pathway. current findings introduce promising anti-cancer treatment human-resistant could be combination chemotherapeutic regimens improve outcome reduce developed resistance.