Low-dose doxorubicin with carotenoids selectively alters redox status and upregulates oxidative stress-mediated apoptosis in breast cancer cells

Vijay, Kariyappa; Sowmya, Poorigali Raghavendra-Rao; Arathi, Bangalore Prabhashankar; Shilpa, Shivaprasad; Shwetha, Hulikere Jagdish; Raju, Murugesan; Baskaran, Vallikannan; Lakshminarayana, Rangaswamy

doi:10.1016/j.fct.2018.06.027

Cited by 72 publications

(44 citation statements)

References 52 publications

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“…Several carotenoids can enhance the toxicity of ROS-inducing anti-cancer drugs. For instance, a study has shown that addition of lutein and β-carotene to ROS-inducing doxorubicin at a low dose of 0.2–3.2 μM is effective against breast cancer cell lines MCF-7 and MDA-MB-231 without influencing the redox status (e.g., lipid peroxides (LPx), ROS, and lactate dehydrogenase levels) in normal breast epithelial MCF 10A cells [ 49 ]. In that study, the combined treatment with carotenoids and doxorubicin enhanced apoptosis of cancer cells by depleting GSH, increasing levels of LPx, and ROS, causing mitochondrial dysfunction, activating caspases-3, -8, and -9, upregulating p21, p27, p53 and Bax, and down-regulating Bcl-2.…”

Section: Carotenoids Act Synergistically With Ros-inducing Anticanmentioning

confidence: 99%

Pro-oxidant Actions of Carotenoids in Triggering Apoptosis of Cancer Cells: A Review of Emerging Evidence

et al. 2020

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Carotenoids are well known for their potent antioxidant function in the cellular system. However, in cancer cells with an innately high level of intracellular reactive oxygen species (ROS), carotenoids may act as potent pro-oxidant molecules and trigger ROS-mediated apoptosis. In recent years, the pro-oxidant function of several common dietary carotenoids, including astaxanthin, β-carotene, fucoxanthin, and lycopene, has been investigated for their effective killing effects on various cancer cell lines. Besides, when carotenoids are delivered with ROS-inducing cytotoxic drugs (e.g., anthracyclines), they can minimize the adverse effects of these drugs on normal cells by acting as antioxidants without interfering with their cytotoxic effects on cancer cells as pro-oxidants. These dynamic actions of carotenoids can optimize oxidative stress in normal cells while enhancing oxidative stress in cancer cells. This review discusses possible mechanisms of carotenoid-triggered ROS production in cancer cells, the activation of pro-apoptotic signaling by ROS, and apoptotic cell death. Moreover, synergistic actions of carotenoids with ROS-inducing anti-cancer drugs are discussed, and research gaps are suggested.

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Section: Carotenoids Act Synergistically With Ros-inducing Anticanmentioning

confidence: 99%

Pro-oxidant Actions of Carotenoids in Triggering Apoptosis of Cancer Cells: A Review of Emerging Evidence

et al. 2020

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“…The enhanced levels of ROS generation have shown a crucial step in carotenoids-induced apoptosis of a variety of cancer cells [33], including fucoxanthin in human leukemia cell HL-60 cells [34], lycopene oxidation products in human prostate cancer MCF-7, PC-3, and HeLa cells [35,36], and lutein in HeLa cells [10]. Therefore, we analyzed whether β-cryptoxanthin could also trigger ROS production in Hela (Figure 3).…”

Section: Ros Including Superoxide ( • O −mentioning

confidence: 99%

Chemopreventive Effect of β-Cryptoxanthin on Human Cervical Carcinoma (HeLa) Cells Is Modulated through Oxidative Stress-Induced Apoptosis

et al. 2019

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The present study was aimed to assess cellular and molecular events involved in the chemopreventive activities of β-cryptoxanthin derived from mandarin oranges (Citrus unshiu Marc.) on human cervical carcinoma (HeLa) cells. In vitro experiments established that β-cryptoxanthin significantly inhibited the proliferation of HeLa cells with the IC50 value of 4.5 and 3.7 µM after 24 and 48 h of treatments, respectively. β-cryptoxanthin-treated HeLa cells exhibited enhanced levels of oxidative stress correlated with significant downregulation of anti-apoptotic Bcl-2, and upregulation of pro-apoptotic Bax mRNA expression. Moreover, β-cryptoxanthin triggered nuclear condensation and disruption of the integrity of the mitochondrial membrane, upregulated caspase-3, -7, and -9 mRNA, and enhanced activation of caspase-3 proteins, resulting in nuclei DNA damage and apoptosis of HeLa cells. Remarkably, TUNEL assay carried out to detect nuclei DNA damage showed 52% TUNEL-positive cells after treatment with a physiological concentration of β-cryptoxanthin (1.0 μM), which validates its potential as an anticancer drug of natural origin.

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“…Previous studies suggested that SLC25A10 was involved in sustaining metabolic shift and redox balance (10,13). Abnormal redox condition was found to be associated with abnormal expression of P21 and P27, thus influencing cell proliferation and mitosis (45,46). CCNE1 is an important gene involved in cell cycle (47).…”

Section: Discussionmentioning

confidence: 99%

SLC25A10 performs an oncogenic role in human osteosarcoma

et al. 2020

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Osteosarcoma is one of the most common primary malignant bone tumors in adolescents. It is associated with high risk of relapse and the outcomes of patients with high-grade osteosarcoma remain poor. Therefore, additional studies investigating the molecular mechanisms involved in tumor initiation, growth, migration and invasion of osteosarcoma are necessary. In the present study, the protein levels of solute carrier family 25 member 10 (SLC25A10) were increased in osteosarcoma tissue, compared with normal bone tissue. In patients with osteosarcoma, high expression levels of SLC25A10 were associated with poor clinicopathological parameters, including metastasis, clinical Enneking stage, relapse-free survival and overall survival rates. Short hairpin RNA knockdown of SLC25A10 significantly suppressed cell proliferation as determined by cell counting, MTT assay and cell colony formation assays. In addition, SLC25A10 knockdown caused an increase in apoptosis and a decrease in mitosis in osteosarcoma cells. Cyclin E1 (CCNE1) was positively regulated by SLC25A10, while P21 and P27 were negatively regulated by SLC25A10. Therefore, SLC25A10 may play an oncogenic role in human osteosarcoma, which could be mediated by CCNE1, P21 and P27.

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Low-dose doxorubicin with carotenoids selectively alters redox status and upregulates oxidative stress-mediated apoptosis in breast cancer cells

Cited by 72 publications

References 52 publications

Pro-oxidant Actions of Carotenoids in Triggering Apoptosis of Cancer Cells: A Review of Emerging Evidence

Pro-oxidant Actions of Carotenoids in Triggering Apoptosis of Cancer Cells: A Review of Emerging Evidence

Chemopreventive Effect of β-Cryptoxanthin on Human Cervical Carcinoma (HeLa) Cells Is Modulated through Oxidative Stress-Induced Apoptosis

SLC25A10 performs an oncogenic role in human osteosarcoma

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