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      Apoptotic Pathway as the Therapeutic Target for Anticancer Traditional Chinese Medicines

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          Abstract

          Cancer is a leading cause of morbidity and mortality worldwide. Apoptosis is a process of programmed cell death and it plays a vital role in human development and tissue homeostasis. Mounting evidence indicates that apoptosis is closely related to the survival of cancer and it has emerged as a key target for the discovery and development of novel anticancer drugs. Various studies indicate that targeting the apoptotic signaling pathway by anticancer drugs is an important mechanism in cancer therapy. Therefore, numerous novel anticancer agents have been discovered and developed from traditional Chinese medicines (TCMs) by targeting the cellular apoptotic pathway of cancer cells and shown clinically beneficial effects in cancer therapy. This review aims to provide a comprehensive discussion for the role, pharmacology, related biology, and possible mechanism(s) of a number of important anticancer TCMs and their derivatives mainly targeting the cellular apoptotic pathway. It may have important clinical implications in cancer therapy.

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          Role of reactive oxygen species (ROS) in apoptosis induction.

          Reactive oxygen species (ROS) and mitochondria play an important role in apoptosis induction under both physiologic and pathologic conditions. Interestingly, mitochondria are both source and target of ROS. Cytochrome c release from mitochondria, that triggers caspase activation, appears to be largely mediated by direct or indirect ROS action. On the other hand, ROS have also anti-apoptotic effects. This review focuses on the role of ROS in the regulation of apoptosis, especially in inflammatory cells.
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            Multiple biological activities of curcumin: a short review.

            Turmeric (Curcuma longa rhizomes), commonly used as a spice is well documented for its medicinal properties in Indian and Chinese systems of medicine. It has been widely used for the treatment of several diseases. Epidemiological observations, though inconclusive, are suggestive that turmeric consumption may reduce the risk of some form of cancers and render other protective biological effects in humans. These biological effects of turmeric have been attributed to its constituent curcumin that has been widely studied for its anti-inflammatory, anti-angiogenic, anti-oxidant, wound healing and anti-cancer effects. As a result of extensive epidemiological, clinical, and animal studies several molecular mechanisms are emerging that elucidate multiple biological effects of curcumin. This review summarizes the most interesting in vitro and in vivo studies on the biological effects of curcumin.
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              Reactive oxygen species: role in the development of cancer and various chronic conditions

              Oxygen derived species such as superoxide radical, hydrogen peroxide, singlet oxygen and hydroxyl radical are well known to be cytotoxic and have been implicated in the etiology of a wide array of human diseases, including cancer. Various carcinogens may also partly exert their effect by generating reactive oxygen species (ROS) during their metabolism. Oxidative damage to cellular DNA can lead to mutations and may, therefore, play an important role in the initiation and progression of multistage carcinogenesis. The changes in DNA such as base modification, rearrangement of DNA sequence, miscoding of DNA lesion, gene duplication and the activation of oncogenes may be involved in the initiation of various cancers. Elevated levels of ROS and down regulation of ROS scavengers and antioxidant enzymes are associated with various human diseases including various cancers. ROS are also implicated in diabtes and neurodegenerative diseases. ROS influences central cellular processes such as proliferation a, apoptosis, senescence which are implicated in the development of cancer. Understanding the role of ROS as key mediators in signaling cascades may provide various opportunities for pharmacological intervention.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                12 July 2019
                2019
                : 10
                : 758
                Affiliations
                [1] 1Department of Pharmacology, School of Pharmacy, Southwest Medical University , Luzhou, China
                [2] 2Department of Pharmacy, Nanchong Central Hospital , Nanchong, China
                [3] 3Department of Pharmacy, Affliated Hospital of Traditional Chinese Medicine, Southwest Medical University , Luzhou, China
                Author notes

                Edited by: Ruiwen Zhang, University of Houston, United States

                Reviewed by: Shivendra Vikram Singh, St. Jude Children’s Research Hospital, United States; Jun Zhao, First Affiliated Hospital of Soochow University, China; Jiumao Lin, Fujian University of Traditional Chinese Medicine, China; Haoyu Ye, Sichuan University, China

                *Correspondence: Shousong Cao, shousongc@ 123456gmail.com ; Xiukin Lin, linxiukun@ 123456yahoo.com

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                †These authors have contributed equally to this work.

                Article
                10.3389/fphar.2019.00758
                6639427
                31354479
                a287dc8b-f3f7-4176-bc45-c2dfe75486ae
                Copyright © 2019 An, Lai, Zhang, Liu, Lin and Cao

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 08 April 2019
                : 11 June 2019
                Page count
                Figures: 8, Tables: 1, Equations: 0, References: 342, Pages: 25, Words: 13316
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                apoptosis,cancer,cancer therapy,traditional chinese medicine,cellular signaling pathway

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