Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Targeted Cancer Therapies and Programmed Cell Death

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 17966

Share This Special Issue

Special Issue Editors

Dr. Hisashi Harada

E-Mail Website
Guest Editor

Philips Institute for Oral Health Research, VCU School of Dentistry, Massey Cancer Center, Richmond, VA, USA
Interests: cancer therapy; cell death; BCL-2 family; drug resistance

Prof. Dr. Nam Deuk Kim

E-Mail Website
Guest Editor

Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea
Interests: cancer; cell death; cell cycle regulation; apoptosis; autophagy; anticancer drug development; chemoprevention; breast cancer; colon cancer; gastric cancer; hepatocellular carcinoma; AOM-DSS model; bile acid; hypoxia; stem cell; differentiation; nutraceuticals; myodifferentiation; sarcopenia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is well known that cell death is regulated by a variety of programmed pathways to maintain cellular homeostasis, and dysregulation of this mechanism is one of the hallmarks of cancer. Direct targeting of cell death mechanisms is an attractive treatment option for cancer therapies. For example, the recent development of pro-survival BCL-2 family inhibitors (BH3 mimetics) to the repertoire of targeted therapies has revealed marked clinical success. Furthermore, targeting other cell death machineries, such as ferroptosis, necroptosis, or autophagy, has been shown to have an alternative therapeutic potential. This Special Issue focuses on molecular mechanisms and therapeutic potential for cancer treatment through a broad range of cell death pathways. We welcome submissions of original papers and reviews on this important area.

Dr. Hisashi Harada
Prof. Dr. Nam Deuk Kim
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

apoptosis
ferroptosis
necroptosis
autophagy
targeted cancer therapy

Published Papers (6 papers)

Download All Papers

Research

Jump to: Review

17 pages, 3487 KiB

Open AccessArticle

Gain-of-Function p53N236S Mutation Drives the Bypassing of HRas^V12-Induced Cellular Senescence via PGC–1α

by Hao Yang, Ke Zhang, Yusheng Guo, Xin Guo, Kailong Hou, Jing Hou, Ying Luo, Jing Liu and Shuting Jia

Int. J. Mol. Sci. 2023, 24(4), 3790; https://doi.org/10.3390/ijms24043790 - 14 Feb 2023

Viewed by 1586

Abstract

One of the key steps in tumorigenic transformation is immortalization in which cells bypass cancer-initiating barriers such as senescence. Senescence can be triggered by either telomere erosion or oncogenic stress (oncogene-induced senescence, OIS) and undergo p53- or Rb-dependent cell cycle arrest. The tumor suppressor p53 is mutated in 50% of human cancers. In this study, we generated p53N236S (p53S) mutant knock-in mice and observed that p53S heterozygous mouse embryonic fibroblasts (p53^S/+) escaped HRas^V12-induced senescence after subculture in vitro and formed tumors after subcutaneous injection into severe combined immune deficiency (SCID) mice. We found that p53S increased the level and nuclear translocation of PGC–1α in late-stage p53^S/++Ras cells (LS cells, which bypassed the OIS). The increase in PGC–1α promoted the biosynthesis and function of mitochondria in LS cells by inhibiting senescence-associated reactive oxygen species (ROS) and ROS-induced autophagy. In addition, p53S regulated the interaction between PGC–1α and PPARγ and promoted lipid synthesis, which may indicate an auxiliary pathway for facilitating cell escape from aging. Our results illuminate the mechanisms underlying p53S mutant-regulated senescence bypass and demonstrate the role played by PGC–1α in this process. Full article

(This article belongs to the Special Issue Targeted Cancer Therapies and Programmed Cell Death)

► Show Figures

Figure 1

20 pages, 4110 KiB

Open AccessArticle

Combination RSL3 Treatment Sensitizes Ferroptosis- and EGFR-Inhibition-Resistant HNSCCs to Cetuximab

by Shujie Liu, Shuai Yan, Jie Zhu, Ruiqing Lu, Chujie Kang, Kang Tang, Jinfeng Zeng, Mingmei Ding, Zixiang Guo, Xianxin Lai, Yinan Jiang, Siqing Wu, Lihua Zhou, Litao Sun and Zhong-Wei Zhou

Int. J. Mol. Sci. 2022, 23(16), 9014; https://doi.org/10.3390/ijms23169014 - 12 Aug 2022

Cited by 10 | Viewed by 3166

Abstract

Head and neck squamous cell carcinomas (HNSCCs) are a type of cancer originating in the mucosal epithelium of the mouth, pharynx, and larynx, the sixth most common cancer in the world. However, there is no effective treatment for HNSCCs. More than 90% of HNSCCs overexpress epidermal growth factor receptors (EGFRs). Although small molecule inhibitors and monoclonal antibodies have been developed to target EGFRs, few EGFR-targeted therapeutics are approved for clinical use. Ferroptosis is a new kind of programmed death induced by the iron catalyzed excessive peroxidation of polyunsaturated fatty acids. A growing body of evidence suggests that ferroptosis plays a pivotal role in inhibiting the tumor process. However, whether and how ferroptosis-inducers (FINs) play roles in hindering HNSCCs are unclear. In this study, we analyzed the sensitivity of different HNSCCs to ferroptosis-inducers. We found that only tongue squamous cell carcinoma cells and laryngeal squamous cell carcinoma cells, but not nasopharyngeal carcinoma cells, actively respond to ferroptosis-inducers. The different sensitivities of HNSCC cells to ferroptosis induction may be attributed to the expression of KRAS and ferritin heavy chain (FTH1) since a high level of FTH1 is associated with the poor prognostic survival of HNSCCs, but knocked down FTH1 can promote HNSCC cell death. Excitingly, the ferroptosis-inducer RSL3 plays a synthetic role with EGFR monoclonal antibody Cetuximab to inhibit the survival of nasopharyngeal carcinoma cells (CNE-2), which are insensitive to both ferroptosis induction and EGFR inhibition due to a high level of FTH1 and a low level of EGFR, respectively. Our findings prove that FTH1 plays a vital role in ferroptosis resistance in HNSCCs and also provide clues to target HNSCCs resistant to ferroptosis induction and/or EGFR inhibition. Full article

(This article belongs to the Special Issue Targeted Cancer Therapies and Programmed Cell Death)

► Show Figures

Figure 1

17 pages, 2596 KiB

Open AccessArticle

MHY2245, a Sirtuin Inhibitor, Induces Cell Cycle Arrest and Apoptosis in HCT116 Human Colorectal Cancer Cells

by Yong Jung Kang, Jung Yoon Jang, Young Hoon Kwon, Jun Ho Lee, Sanggwon Lee, Yujin Park, Young-Suk Jung, Eunok Im, Hyung Ryong Moon, Hae Young Chung and Nam Deuk Kim

Int. J. Mol. Sci. 2022, 23(3), 1590; https://doi.org/10.3390/ijms23031590 - 29 Jan 2022

Cited by 10 | Viewed by 2593

Abstract

Sirtuins (SIRTs), which are nicotinamide adenine dinucleotide-dependent class III histone deacetylases, regulate cell division, survival, and senescence. Although sirtinol, a synthetic SIRT inhibitor, is known to exhibit antitumor effects, its mechanism of action is not well understood. Therefore, we aimed to assess the anticancer effects and underlying mechanism of MHY2245, a derivative of sirtinol, in HCT116 human colorectal cancer cells in vitro. Treatment with MHY2245 decreased SIRT1 activity and caused DNA damage, leading to the upregulation of p53 acetylation, and increased levels of p53, phosphorylation of H2A histone family member X, ataxia telangiectasia and Rad3-related kinase, checkpoint kinase 1 (Chk1), and Chk2. The level of the breast cancer type 1 susceptibility protein was also found to decrease. MHY2245 induced G2/M phase cell cycle arrest via the downregulation of cyclin B1, cell division cycle protein 2 (Cdc2), and Cdc25c. Further, MHY2245 induced HCT116 cell death via apoptosis, which was accompanied by internucleosomal DNA fragmentation, decreased B-cell lymphoma 2 (Bcl-2) levels, increased Bcl-2-asscociated X protein levels, cleavage of poly(ADP-ribose) polymerase, and activation of caspases -3, -8, and -9. Overall, MHY2245 induces cell cycle arrest, triggers apoptosis through caspase activation, and exhibits DNA damage response-associated anticancer effects. Full article

(This article belongs to the Special Issue Targeted Cancer Therapies and Programmed Cell Death)

► Show Figures

Figure 1

Review

Jump to: Research

28 pages, 2310 KiB

Open AccessReview

Mechanism of Resveratrol-Induced Programmed Cell Death and New Drug Discovery against Cancer: A Review

by Jung Yoon Jang, Eunok Im and Nam Deuk Kim

Int. J. Mol. Sci. 2022, 23(22), 13689; https://doi.org/10.3390/ijms232213689 - 08 Nov 2022

Cited by 18 | Viewed by 3313

Abstract

Resveratrol (3,5,4′-trihydroxy-trans-stilbene), a polyphenol found in grapes, red wine, peanuts, and apples, has been reported to exhibit a wide range of biological and pharmacological properties. In addition, resveratrol has been reported to intervene in multiple stages of carcinogenesis. It has also been known to kill several human cancer cells through programmed cell death (PCD) mechanisms such as apoptosis, autophagy, and necroptosis. However, resveratrol has limitations in its use as an anticancer agent because it is susceptible to photoisomerization owing to its unstable double bond, short half-life, and is rapidly metabolized and eliminated. Trans-(E)-resveratrol is nontoxic, and has several biological and pharmacological activities. However, little is known about the pharmacological properties of the photoisomerized cis-(Z)-resveratrol. Therefore, many studies on resveratrol derivatives and analogues that can overcome the shortcomings of resveratrol and increase its anticancer activity are underway. This review comprehensively summarizes the literature related to resveratrol-induced PCD, such as apoptosis, autophagy, necroptosis, and the development status of synthetic resveratrol derivatives and analogues as novel anticancer drugs. Full article

(This article belongs to the Special Issue Targeted Cancer Therapies and Programmed Cell Death)

► Show Figures

Figure 1

31 pages, 3766 KiB

Open AccessReview

Mechanism of Bile Acid-Induced Programmed Cell Death and Drug Discovery against Cancer: A Review

by Jung Yoon Jang, Eunok Im, Yung Hyun Choi and Nam Deuk Kim

Int. J. Mol. Sci. 2022, 23(13), 7184; https://doi.org/10.3390/ijms23137184 - 28 Jun 2022

Cited by 8 | Viewed by 3228

Abstract

Bile acids are major signaling molecules that play a significant role as emulsifiers in the digestion and absorption of dietary lipids. Bile acids are amphiphilic molecules produced by the reaction of enzymes with cholesterol as a substrate, and they are the primary metabolites of cholesterol in the body. Bile acids were initially considered as tumor promoters, but many studies have deemed them to be tumor suppressors. The tumor-suppressive effect of bile acids is associated with programmed cell death. Moreover, based on this fact, several synthetic bile acid derivatives have also been used to induce programmed cell death in several types of human cancers. This review comprehensively summarizes the literature related to bile acid-induced programmed cell death, such as apoptosis, autophagy, and necroptosis, and the status of drug development using synthetic bile acid derivatives against human cancers. We hope that this review will provide a reference for the future research and development of drugs against cancer. Full article

(This article belongs to the Special Issue Targeted Cancer Therapies and Programmed Cell Death)

► Show Figures

Figure 1

22 pages, 600 KiB

Open AccessReview

Role of Induced Programmed Cell Death in the Chemopreventive Potential of Apigenin

by Jung Yoon Jang, Bokyung Sung and Nam Deuk Kim

Int. J. Mol. Sci. 2022, 23(7), 3757; https://doi.org/10.3390/ijms23073757 - 29 Mar 2022

Cited by 20 | Viewed by 2966

Abstract

The flavonoid apigenin (4′,5,7-trihydroxyflavone), which is one of the most widely distributed phytochemicals in the plant kingdom, is one of the most thoroughly investigated phenolic components. Previous studies have attributed the physiological effects of apigenin to its anti-allergic, antibacterial, antidiabetic, anti-inflammatory, antioxidant, antiviral, and blood-pressure-lowering properties, and its documented anticancer properties have been attributed to the induction of apoptosis and autophagy, the inhibition of inflammation, angiogenesis, and cell proliferation, and the regulation of cellular responses to oxidative stress and DNA damage. The most well-known mechanism for the compound’s anticancer effects in human cancer cell lines is apoptosis, followed by autophagy, and studies have also reported that apigenin induces novel cell death mechanisms, such as necroptosis and ferroptosis. Therefore, the aim of this paper is to review the therapeutic potential of apigenin as a chemopreventive agent, as well as the roles of programmed cell death mechanisms in the compound’s chemopreventive properties. Full article

(This article belongs to the Special Issue Targeted Cancer Therapies and Programmed Cell Death)

► Show Figures