Molecular Targets of Curcumin and Future Therapeutic Role in Leukemia

Rafiq, Sara; Raza, Muhammad Hassan; Younas, Mehwish; Naeem, Fariha; Adeeb, Romisha; Iqbal, Javed; Anwar, Pervez; Sajid, Umara; Manzoor, Hafiza Muniba

doi:10.4236/jbm.2018.64003

Cited by 18 publications

(13 citation statements)

References 64 publications

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“…Because several antioxidants stimulate apoptotic pathways and chemotherapy also induces apoptosis by harming DNA, complementary effects between chemotherapeutics and antioxidants exist [94]. The polyphenols, resveratrol, and curcumin exhibit prooxidant and antioxidant effects, whether in combination with other natural antioxidants or classical chemotherapy and may be promising future strategies in chemoprevention and chemotherapy of hematological malignancies [102,103].…”

Section: The Antioxidant Approachmentioning

confidence: 99%

The significant role of redox system in myeloid leukemia: from pathogenesis to therapeutic applications

et al. 2020

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Background Excessive generation of reactive oxygen species (ROS) in the presence of a defective antioxidant system can induce cellular damage and disrupt normal physiological functions. Several studies have revealed the unfavorable role of ROS in promoting the growth, proliferation, migration, and survival of leukemia cells. In this review study, we summarize the mechanisms of ROS production and its role in leukemogenesis, counteractive effects of antioxidants, and implicate the current ROS-dependent anticancer therapies in acute myeloid leukemia. Body The dysregulation of the redox system is known to play a significant role in the pathogenesis of leukemia. Leukemia cells generate high levels of ROS, which further increases the levels through extra pathways, including mitochondrial deoxyribonucleic mutation, leukemic oncogene activation, increased nicotinamide adenine phosphate hydrogen (NADPH), and cytochrome P450 activities. Aforementioned pathways once activated have shown to promote genomic instability, induce drug resistance to leukemia medical therapy, disease relapse and reduce survival period. The current standard of treatment with chemotherapy employs the pro-oxidant approach to induce apoptosis and promote tumor regression. However, this approach retains several deleterious effects on the subject resulting in degradation of the quality of life. Nevertheless, the addition of an antioxidant as an adjuvant drug to chemotherapy alleviates treatment-related toxicity, increases chemotherapeutic efficacy, and improves survival rates of a patient. Conclusion Acute myeloid leukemia remains a daunting challenge to clinicians. The desire to achieve the maximum benefit of chemotherapy but also improve patient outcomes is investigated. ROS generated through several pathways promotes leukemogenesis, drug resistance, and disease relapse. Chemotherapy, the mainstay of treatment, further upregulates ROS levels. Therefore, the addition of an antioxidant to leukemia medical therapy alleviates toxicity and improves patient outcomes.

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Section: The Antioxidant Approachmentioning

confidence: 99%

The significant role of redox system in myeloid leukemia: from pathogenesis to therapeutic applications

et al. 2020

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“…p21 is one of the downstream genes that are being transactivated by p53 90. In fact, curcumin activates p53 directly which repairs DNA and it also inactivates serine/threonine-specific protein kinase (Akt) which resulted in increased expression of Bax gene and induction of apoptosis 91,92…”

Section: Introductionmentioning

confidence: 99%

Role of curcumin in regulating p53 in breast cancer: an overview of the mechanism of action

Talib¹,

Al-hadid²,

Ali³

et al. 2018

BCTT

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p53 is a tumor suppressor gene involved in various cellular mechanisms including DNA repair, apoptosis, and cell cycle arrest. More than 50% of human cancers have a mutated nonfunctional p53. Breast cancer (BC) is one of the main causes of cancer-related deaths among females. p53 mutations in BC are associated with low survival rates and more resistance to the conventional therapies. Thus, targeting p53 activity was suggested as an important strategy in cancer therapy. During the past decades, cancer research was focused on the development of monotargeted anticancer therapies. However, the development of drug resistance by modulation of genes, proteins, and pathways was the main hindrance to the success of such therapies. Curcumin is a natural product, extracted from the roots of Curcuma longa, and possesses various biological effects including anticancer activity. Previous studies proved the ability of curcumin to modulate several signaling pathways and biomolecules in cancer. Safety and cost-effectiveness are additional inevitable advantages of curcumin. This review summarizes the effects of curcumin as a regulator of p53 in BC and the key molecular mechanisms of this regulation.

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“…And with the increased dose of CUR, the expression of P‐gp decreased, and the effective blood concentration of DDP increased. Some studies showed that NF‐κB was the target of CUR to reverse MDR in cancer (Allegra et al, 2017; Rafiq et al, 2018). Ye, Yan, et al (2012) found that MDR in lung cancer cells was mainly associated with two pathways.…”

Section: Application Of Cur In Tumor Mdrmentioning

confidence: 99%

Application of curcumin and its derivatives in tumor multidrug resistance

Guo

et al. 2020

Phytotherapy Research

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Malignant tumor endangers seriously the health of all mankind. Multidrug resistance (MDR) is one of the main causes of clinical tumor chemotherapy failure. Curcumin (CUR) has not only antitumor activity but also reversing tumor MDR effect. CUR reverses tumor MDR via regulating related signal pathways or corresponding expressed proteins or gene. When combined with chemotherapeutic agents, CUR can be a chemotherapeutic sensitive agent to enhance chemotherapy efficacy and weaken tumor MDR. On the other hand, to improve the MDR reversal effect of CUR, its derivatives have been extensively studied. Therefore, this article mainly focuses on reviewing the application of CUR and its derivatives in MDR and its mechanism of reversing MDR.

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Molecular Targets of Curcumin and Future Therapeutic Role in Leukemia

Cited by 18 publications

References 64 publications

The significant role of redox system in myeloid leukemia: from pathogenesis to therapeutic applications

The significant role of redox system in myeloid leukemia: from pathogenesis to therapeutic applications

Role of curcumin in regulating p53 in breast cancer: an overview of the mechanism of action

Application of curcumin and its derivatives in tumor multidrug resistance

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