Effects of daunorubicin: A Synthesis of Findings from 24 Studies

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Original Abstract of the Article

Major Research Findings

Daunorubicin is a widely used anti-cancer drug, but its side effects, such as cardiotoxicity, are a concern. Therefore, research is underway to enhance the effects of daunorubicin and reduce its side effects. 20 found that ginsenosides, components of ginseng, and their metabolites affect the accumulation of daunorubicin in multidrug-resistant cells. Specifically, ginsenoside Rg1 did not affect daunorubicin accumulation, but its metabolite M4, which lacks a sugar moiety, increased accumulation by 3.6-fold at 5 µM. This suggests that metabolites of ginsenosides without glucose moieties may increase daunorubicin accumulation. 3 examined the potential of pomegranate to reduce daunorubicin-induced cardiotoxicity. Pomegranate has significant in vitro free radical scavenging activity, suggesting that it could reduce cardiotoxicity by suppressing reactive oxygen species generated by daunorubicin. 13 investigated the potential effects of bone marrow stromal cells and umbilical cord blood-derived stromal cells on daunorubicin-resistant leukemia cells. These stromal cells may inhibit the growth of leukemia cells. 12 showed that the combination of bortezomib, a proteasome inhibitor, and daunorubicin effectively inhibits the growth of acute leukemia cells and induces apoptosis. 5 investigated the potential of gambogic acid to overcome multidrug resistance (MDR) in daunorubicin-resistant leukemia cells. Gambogic acid may enhance daunorubicin's effectiveness by suppressing PXR (Pregnane X receptor) expression, which causes MDR. 8 explored the possibility of enhancing the antileukemic activity of daunorubicin by modifying its structure. Structural modification of daunorubicin may lead to enhanced anti-cancer activity and reduced side effects. 19 revealed that the combination of magnetic nanoparticles and 5-Bromotetrandrine promotes apoptosis in leukemia cells induced by daunorubicin. These substances may enhance daunorubicin's effects and inhibit the growth of leukemia cells. 9 found that carvedilol has protective effects against daunorubicin-induced cardiomyopathy. Carvedilol, a third-generation, nonselective β-adrenoreceptor antagonist, may suppress the oxidative stress caused by daunorubicin, thereby inhibiting the development of cardiomyopathy. 7 showed that daunorubicin inhibits the expression of Eps8, a protein involved in tumor growth, when inhibiting the growth of leukemia cells. This suggests that daunorubicin may inhibit the growth of leukemia cells by suppressing the expression of Eps8. 17 found that polymethoxyflavonoids inhibit the growth of daunorubicin-resistant leukemia cells and suppress the function of P-gp (P-glycoprotein). Polymethoxyflavonoids may enhance daunorubicin's effects and inhibit the growth of leukemia cells. 22 found that daunorubicin affects the expression of BNP (brain natriuretic peptide) in myocardial cells. BNP is a protein that reduces the burden on the heart, suggesting that daunorubicin may impose a burden on the heart. 23 demonstrated that ebselen has protective effects against daunorubicin-induced cardiomyopathy. Ebselen, a seleno-organic compound with glutathione peroxidase-like and antioxidant activities, may suppress reactive oxygen species generated by daunorubicin, thereby inhibiting the development of cardiomyopathy. 15 found that olmesartan has protective effects against daunorubicin-induced cardiomyopathy. Olmesartan, an angiotensin II receptor blocker, may suppress the oxidative stress caused by daunorubicin, thereby inhibiting the development of cardiomyopathy. 24 showed that pyridoxal 2-chlorobenzoyl hydrazone, an iron chelator, has protective effects against daunorubicin-induced cardiomyopathy. Iron chelators may suppress reactive oxygen species generated by daunorubicin, thereby inhibiting the development of cardiomyopathy. 2 examined the association between CYP3A5 gene polymorphism and the activity of CYP3A and plasma concentrations of daunorubicin in patients with acute leukemia. CYP3A5 is an enzyme that metabolizes daunorubicin, so CYP3A5 gene polymorphisms may affect daunorubicin's blood concentration and side effects. 4 investigated the potential of vitamin K3 and K5 to exhibit anti-cancer effects on daunorubicin-resistant leukemia cells. Vitamin K3 and K5 may inhibit the growth of daunorubicin-resistant leukemia cells. 14 showed that the combination of stealth liposomal daunorubicin and tamoxifen effectively inhibits the growth of breast cancer cells and cancer stem cells. These substances may enhance daunorubicin's effects and inhibit the growth of cancer cells. 18 found that the combination of tandutinib, a FLT3 inhibitor, and cytarabine and daunorubicin effectively inhibits the growth of acute myeloid leukemia cells. These substances may enhance daunorubicin's effects and inhibit the growth of leukemia cells. 16 found that the combination of bortezomib and daunorubicin effectively inhibits the growth of multiple myeloma cells. These substances may enhance daunorubicin's effects and inhibit the growth of myeloma cells. 1 studied the stability and drug release behavior of daunorubicin/cytarabine co-loaded liposomes, considering the interactions between their components. The liposomes were found to be stable and release drugs effectively under acidic conditions. 11 examined the effects of imatinib, daunorubicin, and bortezomib on the growth of Philadelphia chromosome-positive leukemia cells. These substances may inhibit the growth of leukemia cells. 10 found that the combination of 5-bromotetrandrine and daunorubicin promotes apoptosis in daunorubicin-resistant leukemia cells. These substances may enhance daunorubicin's effects and inhibit the growth of leukemia cells. 21 investigated the potential of daunorubicin to promote neuronal differentiation from mouse embryonic stem cells. Daunorubicin may promote neuronal differentiation. 6 examined the potential of cyclin-dependent kinase inhibitors (CDKi) to inhibit the ABCB1 transporter and synergistically enhance the cytotoxic effects of daunorubicin. CDKi may enhance daunorubicin's effects and inhibit the growth of cancer cells.

Benefits and Risks

Benefits Summary

Daunorubicin has been reported to be effective against various types of cancer. It is expected to be effective against leukemia, lymphoma, and solid tumors. Furthermore, daunorubicin has been reported to exhibit synergistic effects when used in combination with other anti-cancer drugs, suggesting that it may enhance the effectiveness of other anti-cancer drugs. Modifications to the administration method of daunorubicin, such as encapsulation in liposomes, may reduce side effects by concentrating daunorubicin in specific locations. 14

Risks Summary

Daunorubicin can cause various side effects, including cardiotoxicity, myelosuppression, and gastrointestinal disorders. Cardiotoxicity is thought to occur due to damage to myocardial cells by daunorubicin, leading to impaired heart function. Myelosuppression is thought to be caused by the suppression of hematopoietic function in the bone marrow by daunorubicin, resulting in a decrease in white blood cells, red blood cells, and platelets. Gastrointestinal disorders are thought to occur due to damage to the gastrointestinal mucosa by daunorubicin, leading to symptoms such as nausea, vomiting, and diarrhea. Additionally, daunorubicin can potentially harm the fetus, so its use should be avoided during pregnancy.

Comparison of Studies

Commonalities of Studies

Many studies have shown that daunorubicin effectively inhibits the growth of various cancer cells. Additionally, daunorubicin has been reported to exhibit synergistic effects when used in combination with other anti-cancer drugs. Moreover, modifications to the administration method of daunorubicin have been shown to potentially reduce side effects.

Differences of Studies

The methods for enhancing daunorubicin's effectiveness and reducing its side effects vary depending on the study. For example, various substances have been studied, including ginsenosides and their metabolites from ginseng, pomegranate, carvedilol, ebselen, olmesartan, iron chelators, vitamin K3 and K5, polymethoxyflavonoids, and FLT3 inhibitors. The objectives of the studies also vary, such as overcoming daunorubicin resistance, suppressing cardiotoxicity, inhibiting the function of P-gp, inhibiting the growth of cancer stem cells, and promoting neuronal differentiation.

Consistency and Inconsistencies of Results

Many studies have shown that daunorubicin has anti-cancer effects. However, further research is needed on safe usage methods due to the potential for side effects such as cardiotoxicity. Additionally, the results regarding the methods for enhancing daunorubicin's effectiveness and reducing side effects vary among studies, necessitating further investigation.

Precautions for Applying Research to Real Life

Daunorubicin should only be used under the guidance of healthcare professionals who can provide appropriate diagnosis and treatment. It is dangerous to use daunorubicin without professional medical advice. Daunorubicin can cause various side effects. Follow the instructions of your doctor when using daunorubicin.

Limitations of Current Research

Research on daunorubicin is still not sufficient. Further research is needed, especially on safe and effective methods for enhancing daunorubicin's effects and reducing side effects. Furthermore, there are still many unanswered questions about the mechanisms of action of daunorubicin, necessitating further research.

Future Research Directions

Research on daunorubicin should proceed in three directions. One is the development of safe and effective methods for enhancing daunorubicin's effects and reducing side effects. The second is to elucidate the mechanisms of action of daunorubicin. The third is to develop new cancer treatments where daunorubicin is expected to be effective.

Conclusion

Daunorubicin has been reported to be effective against various types of cancer. However, it can cause side effects such as cardiotoxicity. It is crucial to follow your doctor's instructions when using daunorubicin. Research on daunorubicin is still not sufficient. Future research is expected to contribute to cancer treatment by developing safe and effective methods for enhancing daunorubicin's effects and reducing side effects.

Literature analysis of 24 papers
Positive Content
23
Neutral Content
1
Negative Content
0
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24
4.

Effects of Vitamin K3 and K5 on Daunorubicin-resistant Human T Lymphoblastoid Leukemia Cells.

Author: NakaokaEri, TanakaSachiko, OndaKenji, SugiyamaKentaro, HiranoToshihiko

Overcomes drug resistance
Suppresses proliferation

This study found that vitamins K3 and K5 inhibited the proliferation of leukemia cells and were effective against drug-resistant cells.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

5.

[Effects of Garcinia Acid Combined with Daunorubicin on Expression of Pregnane X Receptor in Leukemia Cell Line K562/A02].

Author: ZhuHan, ChenBao-An, CaiXiao-Hui, WangFei, GaoChong, ChengJian, ZhangXiao-Ping, DaiLu, XiaGuo-Hua, FuRong, GuoQing-Long

Chemotherapy enhancement

This study suggests that low-dose gambogic acid (GA) can down-regulate PXR gene transcription and protein expression in K562/A02 cells, enhancing cell growth inhibition and increasing the effect of chemotherapy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : Chinese

6.

Purvalanol A, olomoucine II and roscovitine inhibit ABCB1 transporter and synergistically potentiate cytotoxic effects of daunorubicin in vitro.

Author: CihalovaDaniela, HofmanJakub, CeckovaMartina, StaudFrantisek

Anticancer therapy
Dose reduction

Five cyclin-dependent kinase inhibitors (CDKi) were investigated for their interactions with the ABCB1 transporter. Four of the CDKi inhibited efflux of ABCB1 substrates. Co-administration of the tested CDKi with anticancer drugs that are ABCB1 substrates may allow for dose reduction in the treatment of ABCB1-expressing tumors.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

[Effects of daunorubicin on KG1a cell proliferation and Eps8 expression].

Author: GanJin-Ying, XiongWen-Yan, WangLei, CaiSong-Hao, LiYu-Hua

Inhibition of KG1a cell proliferation

Daunorubicin inhibited the proliferation of KG1a cells in a dose and time dependent manner (r = 0.983, P < 0.01). Daunorubicin could reduce the mRNA and protein levels of Eps8 expression in dose and time dependent manners in KG1a cells (r = 0.979, P < 0.05).

English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : Chinese

8.

Effects of structural modifications of daunorubicin on in vitro antileukemic activity.

Author: StojakMarta, MazurLidia, Opydo-ChanekMalgorzata, LukawskaMalgorzata, OszczapowiczIrena

Antileukemic activity

This study investigated the anti-leukemic activity of two new daunorubicin analogs, DAUFmor and DAUFhex, compared to daunorubicin. Both analogs showed weaker anti-leukemic activity than daunorubicin, but DAUFmor appeared to be more active than DAUFhex in ML-1 cells.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Carvedilol-Afforded Protection against Daunorubicin-Induced Cardiomyopathic Rats In Vivo: Effects on Cardiac Fibrosis and Hypertrophy.

Author: ArozalWawaimuli, SariFlori R, WatanabeKenichi, ArumugamSomasundaram, VeeraveeduPunniyakoti T, MaMeilei, ThandavarayanRajarajan A, SukumaranVijayakumar, LakshmananArun Prasath, KobayashiYoshiyasu, MitoSayaka, SoetiknoVivian, SuzukiKenji

Attenuated myocardial fibrosis and hypertrophy
Increased survival rate
Prevented systolic and diastolic dysfunction

This study investigated the effects of carvedilol, a β-adrenoreceptor antagonist, on daunorubicin-induced cardiomyopathic rats.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

10.

[Effects of 5-bromotetrandrine and daunorubicin on apoptosis and expression of survivin in K562/A02 cells].

Author: CaiXiao-Hui, ChenBao-An, ChengJian, WangJun, DingJia-Hua, BaoWen, ZhongYue-Jiao, GaoFeng, XuWen-Lin, ShenHui-Ling, WeiHu-Lai, ChenJing

Leukemia treatment

The combination of 5-bromotetrandrine (5-BrTet) and daunorubicin (DNR) was found to be effective in reversing multidrug resistance in K562/A02 leukemia cells, promoting apoptosis, and downregulating the expression of survivin mRNA and protein. The combination therapy showed a higher apoptotic rate and lower survivin expression compared to treatment with BrTet or DNR alone.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : Chinese

11.

[The anti-leukemic effects of imatinib, daunorubicin and bortezomib on two leukemia cell lines with Ph(+)].

Author: YangXi, YangLei, GongYu-ping, ChangHong, ZhouRui-qing, XingHong-yuan, ZhengBo-hui

Anti-cancer effects

Imatinib, daunorubicin, and bortezomib showed anti-cancer effects on Ph(+) leukemia cells in vitro.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : Chinese

12.

[Effects of bortezomib combined with daunorubicin on proliferation and apoptosis in primary adult acute leukemia].

Author: ZhouRui-qing, GongYu-ping, ZhengBo-hui, YangXi

Increased apoptosis
Synergistic effect

Bortezomib (Bor) in combination with daunorubicin (DNR) showed synergistic effects in promoting apoptosis and inhibiting proliferation of primary leukemia cells in vitro.

English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : Chinese

13.

Effects of bone marrow stromal cells and umbilical cord blood-derived stromal cells on daunorubicin-resistant residual Jurkat cells.

Author: LiangX, HaoL, ChenX, ZhangX, KongP, PengX, GaoL, ZhangC, WangQ

Reversed drug resistance

Both bone marrow stromal cells (BMSCs) and umbilical cord blood-derived stromal cells (UCBDSCs) can reconstruct the leukemic hematopoietic inductive microenvironment and reverse drug resistance in Jurkat/DNR cells. UCBDSCs are more effective than BMSCs in this regard.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

14.

Effects of stealth liposomal daunorubicin plus tamoxifen on the breast cancer and cancer stem cells.

Author: GuoJia, ZhouJie, YingXue, MenYing, LiRuo-Jing, ZhangYan, DuJu, TianWei, YaoHong-Juan, WangXiao-Xing, JuRui-Jun, LuWan-Liang

Eradicated cancer cells
Eradicated cancer stem cells

Stealth liposomal daunorubicin plus tamoxifen showed potential to eradicate both breast cancer cells and cancer stem cells, leading to improved antitumor activity in a mouse model.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

Beneficial effects of angiotensin II receptor blocker, olmesartan, in limiting the cardiotoxic effect of daunorubicin in rats.

Author: ArozalWawaimuli, WatanabeKenichi, VeeraveeduPunniyakoti T, ThandavarayanRajarajan A, HarimaMeilei, SukumaranVijayakumar, SuzukiKenji, TachikawaHitoshi, KodamaMakoto, AizawaYoshifusa

Reduced cardiac toxicity

Olmesartan, an angiotensin II receptor blocker (ARB), reduces cardiac toxicity in rats treated with daunorubicin. The results suggest that Ang II and oxidative stress play a role in anthracycline-induced cardiotoxicity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

Combined effects of bortezomib and daunorubicin on multiple myeloma cell KM3 in vitro.

Author: OuyangGui-Fang, LinMao-Fang

Multiple myeloma treatment

Bortezomib (Bor) combined with daunorubicin (DNR) showed a synergistic inhibitory effect on human multiple myeloma cell line KM3 in vitro, indicating a potential for combined therapy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

18.

The FLT3 inhibitor tandutinib (formerly MLN518) has sequence-independent synergistic effects with cytarabine and daunorubicin.

Author: SchittenhelmMarcus M, KampaKerstin M, YeeKevin W H, HeinrichMichael C

AML treatment
Chemotherapy dose reduction
Cardiac toxicity
Mucositis
Myelosuppression

Tandutinib, a FLT3 inhibitor, demonstrates synergistic anti-leukemic effects when combined with standard chemotherapy for acute myeloid leukemia (AML), particularly in patients with FLT3 internal tandem duplications (ITD).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

19.

Effects of magnetic nanoparticle of fe(3)o(4) and 5-bromotetrandrine on apoptosis of K562/A02 leukemic cells induced by daunorubicin.

Author: ShenMing-Fang, ChenBao-An, ChengJian, GaoFeng, XuWen-Lin, DingJia-Hua, GaoChong, SunXin-Chen, LiGuo-Hong, ChenWen-Ji, LiuLi-Jie, LiXiao-Mao, WangXue-Mei

Leukemia treatment

This study investigated the potential benefits of combination therapy with magnetic nanoparticles of Fe(3)O(4) and 5-Bromotetrandrine (5-BrTet) for chronic leukemia. Apoptosis was assessed using flow cytometry (FCM), Wright staining, and light microscopy, while BAX and BCL-2 expression levels were measured by Western blot. The combination of daunorubicin (DNR) with either MNP (Fe(3)O(4)) or 5-BrTet showed potent cytotoxic effects on K562/A02 cells. Moreover, co-treatment with MNP (Fe(3)O(4)) and 5-BrTet synergistically enhanced DNR-induced apoptosis in K562/A02 cells, leading to typical apoptotic morphological features. BCL-2 expression was significantly reduced, and BAX expression was markedly increased. The study concluded that MNP (Fe(3)O(4)) or 5-BrTet with DNR can induce apoptosis in K562/A02 cells, demonstrating a synergistic effect when used together. The down-regulation of BCL-2 and up-regulation of BAX may play crucial roles in this effect.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

21.

Effects of daunorubicin on ganglioside expression and neuronal differentiation of mouse embryonic stem cells.

Author: LeeDae-Hoon, KooDeog-Bon, KoKinarm, KoKisung, KimSun-Mi, JungJi-Ung, RyuJae-Sung, JinJung-Woo, YangHyo-Jung, DoSu-Il, JungKyu-Yong, ChooYoung-Kug

Neuronal differentiation

Daunorubicin, a chemotherapy drug, was found to increase the expression of gangliosides, especially GQ1b, in differentiating neuronal cells. GQ1b appears to play a role in neurite formation.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

22.

[Effects of daunorubicin on the expression of brain natriuretic peptide gene in myocardial cells: an in vitro experiment with cultured myocardial cells from rats].

Author: WangCong-jun, LiuYa-li, PengHua

Daunorubicin (DNR) suppressed the expression of brain natriuretic peptide (BNP) in myocardial cells. While fructose-1, 6-diphosphate (FDP) did not reverse the suppressing effect of DNR, it did not significantly exacerbate the effect either.

English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : Chinese

24.

Cardioprotective effects of a novel iron chelator, pyridoxal 2-chlorobenzoyl hydrazone, in the rabbit model of daunorubicin-induced cardiotoxicity.

Author: SterbaMartin, PopelováOlga, SimunekTomás, MazurováYvona, PotácováAnna, AdamcováMichaela, KaiserováHelena, PonkaPremysl, GerslVladimír

Cardiotoxicity protection
Negative results at higher dose

This study examines the protective effects of pyridoxal 2-chlorobenzoyl hydrazone (o-108), a potent iron chelator, against daunorubicin (DAU)-induced chronic cardiotoxicity in rabbits. The study demonstrates that o-108 can effectively shield against DAU-induced cardiac damage, indicating its potential as a cardioprotective agent in patients receiving anthracycline chemotherapy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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