• 약학회지
• /
• 제42권5호
• /
• pp.507-512
• /
• 1998

In the course of developing novel antitumor intercalating agents. We synthesized 4-carbamoyloxymethyl-l-azaanthraquinones 7-12, incorporating the latent alkylating functi onality. These compounds were designed to explore the effect of substituent on the nitrogen of carbamate. The target compounds were prepared by hetero Diels-Alder reaction as a key step followed by functionalization of benzylic methyl to the desired substituents. Growth inhibitory studies of the azaanthraquinones were conducted in vitro against human cancer cell lines (SNU-354; liver and MCF7; breast) and human epidermoid carcinoma cells that are sensitive (KB-3-1) and multidrug-resistant (KB-V-1). The compounds were less potent than doxorubicin against sensitive cell lines. However, the most active compound 12 was not cross-resistant with doxorubicin against KB-V-1.

• 약학회지
• /
• 제41권6호
• /
• pp.718-723
• /
• 1997

In the course of developing novel antitumor intercalating agents, we synthesized 3- carbamoyloxymethyl-azaanthraquinones 6-12, incorporating the latent alkylating functionality. These compounds were designed to explore the effect of heteroatom incorporation into anthraquinone chromophore and the effect of the incorporation of the latent alkylating functionality. The derivatives were prepared by hetero Diels-Alder reaction as a key step followed by functionality of allylic methyl to the desired substituents. Growth inhibitory studies of the azaanthraquinones were conducted in vitro against human cancer cell lines (SNU-354: liver and MCF7: breast) and human epidermoid carcinoma cells that are sensitive (KB-3-1) and multidrug-resistant (KB-V-1). The derivatives were 10 to 100-fold less potent than doxorubicin against sensitive cell lines. However, they were marginally cross-resistant with doxorubicin against KB-V-1.

• Journal of Microbiology and Biotechnology
• /
• 제29권11호
• /
• pp.1799-1805
• /
• 2019

Doxorubicin (DOX) is one of the most effective anticancer agents used for the treatment of multiple cancers; however, its use is limited by its short half-life and adverse drug reactions, especially cardiotoxicity. In this study, we found that the conjugate of DOX with APTA12 (Gemcitabine incorporated G-quadruplex aptamer) was significantly more cancer selective and cytotoxic than DOX. The conjugate had an affinity for nucleolin, with higher uptake and retention into the cancer cells than those of DOX. Further, it was localized to the nucleus, which is the target site of DOX. Owing to its mechanism of action, DOX has the ability to intercalate into the nucleotides thus making it a suitable drug to form a conjugate with cancer selective aptamers such as APTA12. The conjugation can lead to selectively accumulate in the cancer cells thus decreasing its potential nonspecific as well as cardiotoxic side effects. The aim of this study was to prepare a conjugate of DOX with APTA12 and assess the chemotherapeutic properties of the conjugate specific to cancer cells. The DOX-APTA12 conjugate was prepared by incubation and its cytotoxicity in MCF-10A (non-cancerous mammary cells) and MDA-MB-231 (breast cancer cells) was assessed. The results indicate that DOX-APTA12 conjugate is a potential option for chemotherapy especially for nucleolin expressing breast cancer with reduced doxorubicin associated side effects.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권1호
• /
• pp.179-184
• /
• 2014

Chemoresistance of breast cancer to doxorubicin is mediated mainly through activation of NF-kB and over expression of HER2. Curcumin and its analogues (PGV-0 and PGV-1) exert cytotoxic effects on T47D breast cancer cells. Suppression of NF-kB activation is suggested to contribute to this activity. The present study aimed to explore the effects of curcumin, PGV-0, and PGV-1 singly and in combination with doxorubicin on MCF-7/Dox cells featuring over-expression of HER2. In MTT assays, curcumin, PGV-0, and PGV-1 showed cytotoxicity effects against MCF-7/Dox with IC50 values of $80{\mu}M$, $21{\mu}M$, and $82{\mu}M$ respectively. These compounds increased MCF-7/Dox sensitivity to doxorubicin. Cell cycle distribution analysis exhibited that the combination of curcumin and its analogues with Dox increased sub G-1 cell populations. Curcumin and PGV-1 but not PGV-0 decreased localization of p65 into the nucleus induced by Dox, indicating that activation of NF-kB was inhibited. Molecular docking of curcumin, PGV-0, and PGV-1 demonstrated high affinity to HER2 at ATP binding site. This interaction were directly comparable with those of ATP and lapatinib. These findings suggested that curcumin, PGV-0 and PGV-1 enhance the Dox cytotoxicity to MCF-7 cells through inhibition of HER2 activity and NF-kB activation.

• Archives of Pharmacal Research
• /
• 제21권6호
• /
• pp.749-752
• /
• 1998

Six 3-dialkylaminomethyl-1-azaanthraquinones and five 4-dialkylaminomethyl-1-azaanthraquinones were synthesized and evaluated in vitro cytotoxicity against four human can cer cell lines. The compounds retained much of their cytotoxic activity against the multi-drug-resistant cell line (KB-V-1) as shown by resistance index.

• Archives of Pharmacal Research
• /
• 제23권5호
• /
• pp.450-454
• /
• 2000

Eight 2-alkylaminosubstituted 5,8-dimethoxy-4-methylquinolines and nine 2-alkylaminosub-stituted or 2,6-disubstituted 4-methylquinoline-5,8-diones were synthesized and evaluated in vitro cytotoxicity against four human cancer cell lines (HOP62, SK-OV-3, HCT15 and SF295).

• 센서학회지
• /
• 제32권6호
• /
• pp.412-417
• /
• 2023

There is increasing interest in the rapid and highly sensitive monitoring of cell viability in biological and toxicological research. Conventional methods depend on optical assays using Water Soluble Tetrazolium-8 (WST-8) or 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay, which requires a large volume of samples and special instruments, necessitating shipment of clinical samples to laboratories. This paper reports on the development of a rapid and sensitive electrochemical (EC) sensor using screen printed electrode (SPE) and surface modification using 4'-mercapto-N-phenylquinone diamine (4'-NPQD), as double electron mediators, for monitoring cell viability via the measurement of nicotinamide adenine dinucleotide (NADH). We used the sensor to observe the viability of MCF-7 and doxorubicin (Dox)-treated cells. The oxidation current of NADH was measured via chronoamperometry (CA), and the EC results showed a good linear relationship when compared with NADH quantification using WST-8 assay. The analysis time was only 10 s and limit of detection (LOD) of NADH was 1.78 µM. Our EC method has the potential to replace conventional WST assays for cell viability and cytotoxicity experiments.

• Biotechnology and Bioprocess Engineering:BBE
• /
• 제9권4호
• /
• pp.261-266
• /
• 2004

Hyperthermia (HT) in combination with anticancer drugs (ACDs) had proven to more efficacious in various cancers, although efficacies vary according to chemotherapeutic compounds and cancer types. Presently there are few data that compares anticancer efficacies among ACDs under hyperthermic conditions. Therefore, we selected three commonly used ACDs (quercetin, verapamil and doxorubicin) and compared their antitumor effects when each was treated with 43$^{\circ}C$ HT exposure. Firstly, FM3A, a murine breast cancer cell line, was treated with each ACD for 1 h followed by 43$^{\circ}C$ exposure for additional 1 h, and examined the effects of: 1) each drug, 2) 43$^{\circ}C$ HT exposure, and 3) the combination of each drug and 43$^{\circ}C$ HT exposure for 1, 6 and 24 h. The determined overall effects on FM3A cells were arrested cell proliferation, clonogenic efficiency and apoptosis. Pre-treatment of FM3A cells to each ACD followed by 43$^{\circ}C$ HT exposure produced greater antitumor effects including suppressed cell proliferation, reduced clonogenic efficiency and increased apoptotic cell death, compared to ACD treatment or HT exposure alone. Apoptotic cell death occurred in a time-dependent manner. Among the ACDs, antitumor efficacies varied in the order of doxorubicin > verapamil > quercetin. It was concluded that heat exposure during ACD treatment of caner cells may be an important factor to get a better antitumor benefit, even though this benefit may differ from one drug to another.

• BMB Reports
• /
• 제50권6호
• /
• pp.335-340
• /
• 2017

Although doxorubicin (Dox)-induced oxidative stress is known to be associated with cytotoxicity, the precise mechanism remains unclear. Genotoxic stress not only generates free radicals, but also affects actin cytoskeleton stability. We showed that Dox-induced RhoA signaling stimulated actin cytoskeleton alterations, resulting in central stress fiber disruption at early time points and cell periphery cortical actin formation at a later stage, in HeLa cells. Interestingly, activation of a cofilin phosphatase, chronophin (CIN), was initially evoked by Dox-induced RhoA signaling, resulting in a rapid phosphorylated cofilin turnover leading to actin cytoskeleton remodeling. In addition, a novel interaction between CIN and $14-3-3{\zeta}$ was detected in the absence of Dox treatment. We demonstrated that CIN activity is quite contrary to $14-3-3{\zeta}$ binding, and the interaction leads to enhanced phosphorylated cofilin levels. Therefore, initial CIN activation regulation could be critical in Dox-induced actin cytoskeleton remodeling through RhoA/cofilin signaling.

• The Korean Journal of Physiology and Pharmacology
• /
• 제26권3호
• /
• pp.145-155
• /
• 2022

Multidrug resistance of tumors has been a severe obstacle to the success of cancer chemotherapy. The study wants to investigate the reversal effects of imperatorin (IMP) on doxorubicin (DOX) resistance in K562/DOX leukemia cells, A2780/Taxol cells and in NOD/SCID mice, to explore the possible molecular mechanisms. K562/DOX and A2780/Taxol cells were treated with various concentrations of DOX and Taol with or without different concentrations of IMP, respectively. K562/DOX xenograft model was used to assess anti-tumor effect of IMP combined with DOX. MTT assay, Rhodamine 123 efflux assay, RT-PCR, and Western blot analysis were determined in vivo and in vitro. Results showed that IMP significantly enhanced the cytotoxicity of DOX and Taxol toward corresponding resistance cells. In vivo results illustrated both the tumor volume and tumor weight were significantly decreased after 2-week treatment with IMP combined with DOX compared to the DOX alone group. Western blotting and RT-PCR analyses indicated that IMP downregulated the expression of P-gp in K562/DOX xenograft tumors in NOD/SCID mice. We also evaluated glycolysis and glutamine metabolism in K562/DOX cells by measuring glucose consumption and lactate production. The results revealed that IMP could significantly reduce the glucose consumption and lactate production of K562/DOX cells. Furthermore, IMP could also remarkably repress the glutamine consumption, α-KG and ATP production of K562/DOX cells. Thus, IMP may sensitize K562/DOX cells to DOX and enhance the antitumor effect of DOX in K562/DOX xenograft tumors in NOD/SCID mice. IMP may be an adjuvant therapy to mitigate the multidrug resistance in leukemia chemotherapy.