Abstract

Several chalcones were synthesized and their in vitro cytotoxicity against various human cell lines, including human breast adenocarcinoma cell line MCF-7, human lung adenocarcinoma cell line A549, human prostate cancer cell line PC3, human adenocarcinoma cell line HT-29 (colorectal cancer) and human normal liver cell line WRL-68 was evaluated. Most of the compounds being active cytotoxic agents, four of them with minimal IC50 values were chosen and studied in detail with MCF-7 cells. The compounds 1, 5, 23, and 25 were capable in eliciting apoptosis in MCF-7 cells as shown by multiparameter cytotoxicity assay and caspase-3/7, -8, and -9 activities (p < 0.05). The ROS level showed 1.3-fold increase (p < 0.05) at the low concentrations used and thus it was concluded that the compounds increased the ROS level eventually leading to apoptosis in MCF-7 cells through intrinsic as well as extrinsic pathways.

Highlights

  • The burden of cancer is increasing across the World and it is the leading cause of deaths in economically developed countries and second leading cause of deaths in developing countries [1].Cancer is considered to be one of the most intractable diseases because of the innate characteristics of cancer cells to proliferate uncontrollably, avoid apoptosis, invade and metastasize [2]

  • The physiologically determined cell death, apoptosis, is necessary to maintain tissue homeostasis; where homeostasis refers to the balance between cell proliferation and cellular loss

  • Since it provides a mechanism of autodigestion for cells that are not functioning properly, the screening of anticancer agents for chemotherapy is designed to identify agents that selectively kill tumor cells

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Summary

Introduction

Cancer is considered to be one of the most intractable diseases because of the innate characteristics of cancer cells to proliferate uncontrollably, avoid apoptosis, invade and metastasize [2]. Despite the advances in chemotherapy, there are no sufficient clinically useful cytotoxic agents that selectively targets cancer cells. Most of the chemotherapeutic agent have anticancer activity thanks to their capacity to elicit apoptosis [3]. The physiologically determined cell death, apoptosis, is necessary to maintain tissue homeostasis; where homeostasis refers to the balance between cell proliferation and cellular loss. Since it provides a mechanism of autodigestion for cells that are not functioning properly, the screening of anticancer agents for chemotherapy is designed to identify agents that selectively kill tumor cells

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