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RISS 인기검색어
- 검색키워드
- 저자 : ( Prasanta Dey ) (검색결과 4 건)
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Therapeutic value of steroidal alkaloids in cancer: Current trends and future perspectives
Dey, Prasanta,Kundu, Amit,Chakraborty, Hirak Jyoti,Kar, Babli,Choi, Wahn Soo,Lee, Byung Mu,Bhakta, Tejendra,Atanasov, Atanas G.,Kim, Hyung Sik Alan R. Liss, Inc 2019 International journal of cancer Vol.145 No.7
<P>Discovery and development of new potentially selective anticancer agents are necessary to prevent a global cancer health crisis. Currently, alternative medicinal agents derived from plants have been extensively investigated to develop anticancer drugs with fewer adverse effects. Among them, steroidal alkaloids are conventional secondary metabolites that comprise an important class of natural products found in plants, marine organisms and invertebrates, and constitute a judicious choice as potential anti‐cancer leads. Traditional medicine and modern science have shown that representatives from this compound group possess potential antimicrobial, analgesic, anticancer and anti‐inflammatory effects. Therefore, systematic and recapitulated information about the bioactivity of these compounds, with special emphasis on the molecular or cellular mechanisms, is of high interest. In this review, we methodically discuss the <I>in vitro</I> and <I>in vivo</I> potential of the anticancer activity of natural steroidal alkaloids and their synthetic and semi‐synthetic derivatives. This review focuses on cumulative and comprehensive molecular mechanisms, which will help researchers understand the molecular pathways involving steroid alkaloids to generate a selective and safe new lead compound with improved therapeutic applications for cancer prevention and therapy. <I>In vitro</I> and <I>in vivo</I> studies provide evidence about the promising therapeutic potential of steroidal alkaloids in various cancer cell lines, but advanced pharmacokinetic and clinical experiments are required to develop more selective and safe drugs for cancer treatment.</P>
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( Sachan Richa ),( Prasanta Dey ),( Chaeun Park ),( Jungho Yang ),( Ji Yeon Son ),( Jae Hyeon Park ),( Su Hyun Lee ),( Mee-young Ahn ),( In Su Kim ),( Hyung Ryong Moon ),( Hyung Sik Kim ) 한국응용약물학회 2020 Biomolecules & Therapeutics(구 응용약물학회지) Vol.28 No.2
Histone deacetylase (HDAC) inhibitors represent a novel class of anticancer agents, which can be used to inhibit cell proliferation and induce apoptosis in several types of cancer cells. In this study, we investigated the anticancer activity of MHY4381, a newly synthesized HDAC inhibitor, against human prostate cancer cell lines and compared its efficacy with that of suberoylanilide hydroxamic acid (SAHA), a well-known HDAC inhibitor. We assessed cell viability, apoptosis, cell cycle regulation, and other biological effects in the prostate cancer cells. We also evaluated a possible mechanism of MHY4381 on the apoptotic cell death pathway. The IC<sub>50</sub> value of MHY4381 was lower in DU145 cells (IC<sub>50</sub>=0.31 µM) than in LNCaP (IC<sub>50</sub>=0.85 µM) and PC-3 cells (IC<sub>50</sub>=5.23 µM). In addition, the IC<sub>50</sub> values of MHY4381 measured in this assay were significantly lower than those of SAHA against prostate cancer cell lines. MHY4381 increased the levels of acetylated histones H3 and H4 and reduced the expression of HDAC proteins in the prostate cancer cell lines. MHY4381 increased G2/M phase arrest in DU145 cells, and G1 arrest in LNCaP cells. It also activated reactive oxygen species (ROS) generation, which induced apoptosis in the DU145 and LNCaP cells by increasing the ratio of Bax/Bcl-2 and releasing cytochrome c into the cytoplasm. Our results indicated that MHY4381 preferentially results in antitumor effects in DU145 and LNCaP cells via mitochondria-mediated apoptosis and ROS-facilitated cell death pathway, and therefore can be used as a promising prostate cancer therapeutic.
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Tae, In Hwan,Park, Eun Young,Dey, Prasanta,Son, Ji Yeon,Lee, Seok-Yong,Jung, Jee h.,Saloni, Saloni,Kim, Mi-Hyun,Kim, Hyung Sik D.A. Spandidos 2018 International journal of oncology Vol.53 No.6
<P>Clinically relevant sirtuin (SIRT) inhibitors may possess antitumor activities. A previous study indicated that 15-deoxy-Δ<SUP>12,14</SUP>-prostaglandin J<SUB>2</SUB> (15d-PGJ<SUB>2</SUB>) exhibited potent anticancer activity by SIRT1 inhibition. Therefore, the aim of the present study was to investigate whether its derivatives (J11-C1 and J19) exhibited anticancer activity against ovarian cancer SKOV3 cells. Cell viability was determined using an MTT assay. Cell cycle arrest, apoptosis and autophagy were determined using flow cytometry or western blot analysis. J11-Cl and J19 were less cytotoxic to SKOV3 cells compared with 15d-PGJ<SUB>2</SUB>. Molecular docking studies supported the interactions of 15d-PGJ<SUB>2</SUB>, J11-Cl and J19 with various amino acids in SIRT1 proteins. Similar to 15d-PGJ<SUB>2</SUB>, J11-C1 and J19 inhibited SIRT1 enzymatic activity and decreased SIRT1 expression levels in a concentration-dependent manner. J11-C1 induced apoptotic cell death more effectively compared with J19, which was associated with markedly decreased expression of the anti-apoptotic molecule B-cell lymphoma 2 (Bcl-2). Furthermore, the levels of light chain 3-II (LC3-II) and beclin-1 were clearly induced in SKOV3 cells treated with J11-Cl. Thus, 15d-PGJ<SUB>2</SUB> and its derivatives exhibited anticancer activity possibly by inducing apoptotic or autophagic cell death pathways. Collectively, the results of the present study suggest that 15d-PGJ<SUB>2</SUB> and its derivatives exerted antitumor activity by selectively modulating the expression of genes associated with cell cycle arrest, apoptosis and autophagy. Notably, J11-C1 is a novel candidate SIRT1 inhibitor with anticancer activity.</P>
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Lee, Suk Hun,Kim, Kunyoung,Jeon, Yeong Uk,Kundu, Amit,Dey, Prasanta,Hwang, Jong Yeon,Mishra, Neeraj Kumar,Kim, Hyung Sik,Kim, In Su Elsevier 2019 Tetrahedron letters: the international organ for t Vol.60 No.34
<P><B>Abstract</B></P> <P>The synthesis of 3,3′-bis-7-indolylmethane derivatives is important for their further development as pharmaceutical compounds and other synthetic purposes. Herein, we describe the zinc- or acid-mediated cross-coupling reaction of 7-azaindoles with aldehydes, such as paraformaldehyde, alkyl aldehydes, aryl aldehydes, enal, and α-ketoaldehyde, providing the corresponding C3-linked bis-7-azaindole derivatives, which are a crucial class towards the development of novel bioactive compounds. High levels of site selectivity and functional group tolerance were observed. Synthesized 3,3′-bis-7-azaindole derivatives were evaluated against human breast adenocarcinoma cells (MCF-7) and human ovarian carcinoma cells (SKOV-3), respectively. Notably, compounds <B>3s</B> and <B>4e</B> displayed promising anticancer properties competitive with anticancer doxorubicin as a positive control.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Lewis acid-mediated synthesis of 3,3′-bis-7-azaindolylmethane derivatives. </LI> <LI> The structure-activity relationship on 7-azaindole ring and methylene moiety. </LI> <LI> Some synthetic products displaying potent cytotoxicity competitive with doxorubicin. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
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