Long-Term Yogic Intervention Improves Symptomatic Scale and Quality of Life by Reducing Inflammatory Cytokines and Oxidative Stress in Breast Cancer Patients Undergoing Chemotherapy and/or Radiotherapy: A Randomized Control Study.

INTRODUCTION: Inflammation has been associated with tumor proliferation and metastasis in breast cancer. Yoga is an ancient therapy that helps in reducing inflammation and improves the patient's quality of life (QoL) and fatigue. In the current study, we investigated the effects of long-term yogic intervention at different time points on the level of inflammatory cytokines and oxidative stress, along with the symptomatic scale and QoL in stage II/III breast cancer patients. METHODS: Ninety-six stage II/III breast cancer patients receiving chemotherapy and/or radiotherapy were enrolled and divided into two groups, non-yoga (Group I) and yoga (Group II). Participants in Group II practiced yoga five days per week for 48 weeks. The European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC-QLQ30) was used to measure the QoL and symptomatic scale. Serum levels of pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ) and granulocyte macrophage colony-stimulating factor (GM-CSF), and oxidative stress markers, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and nitric oxide (NO) were measured at baseline, 16, 32, and 48 weeks in both groups. RESULTS: Yoga significantly (p<0.05) reduced the level of IFN-γ, TNF-α, and MDA and improved QoL (p<0.001) and symptomatic scale (p<0.05) in Group II patients compared to Group I. NO was upregulated in Group I whereas in Group II, it was neither decreased nor increased. CONCLUSION: These findings suggest that yoga may reduce levels of inflammatory cytokines and improve QoL and symptomatic scale in breast cancer patients receiving chemotherapy and/or radiotherapy. Yoga can be an important additional therapy during cancer treatments to cope with treatment side effects including fatigue, depression, and immunological profile, which directly affects the patient's quality of life.

Long-term yogic intervention decreases serum interleukins IL-10 and IL-1ß and improves cancer-related fatigue and functional scale during radiotherapy/chemotherapy in breast cancer patients: a randomized control study.

PURPOSE: Yoga improved fatigue and immunological profile in cancer survivors and has been a promising alternative therapy. Breast cancer treatments are rapidly improving, along with their side effects. This article investigated the effect of the yogic intervention at a different time interval during radiotherapy/chemotherapy on the pro- and anti-inflammatory interleukins along with the cancer-related fatigue and functional scale among patients with stage II/III breast cancer. METHODS: A total of 96 stage II/III breast cancer patients were enrolled in this study and randomly divided into two different groups. Group I (non-Yoga) received chemotherapy and/or radiotherapy and group II (Yoga) received an additional yogic intervention. Both groups were followed up for a period of 48 weeks and blood was collected at the time of enrollment, 16, 32, and 48 weeks, and serum was isolated to measure the pro- and anti-inflammatory interleukins, fatigue, and functional scale questionnaire obtained at each time point. RESULTS: Breast cancer patients in group II showed a significant improvement (p < 0.05) in the functional scale and fatigue from baseline to 48 weeks compared to group I. The yogic intervention significantly decreased (p < 0.05) the level of pro-inflammatory interleukin IL-1ß and pleiotropic interleukin IL-10 in group II compared to group I. CONCLUSION: These finding suggested that improved fatigue and functional scale is associated with a lower level of IL-1ß and IL-10. Yoga may be an important additional therapy along with the cancer treatment to help the patients with cancer-related fatigue and improve their overall immunological profile.

Genistein potentiates Centchroman induced antineoplasticity in breast cancer via PI3K/Akt deactivation and ROS dependent induction of apoptosis.

AIMS: Recently, strategies of cancer treatment using combination of agents with distinct molecular mechanism(s) of action are considered more promising due to its high efficacy and reduced systemic toxicity. The study is aimed to improve the efficacy of selective estrogen receptor modulator, Centchroman (CC) by combination with the phytoestrogen Genistein (GN). METHODS: Cytotoxicity was evaluated by Sulforhodamine B assay. Cell cycle analysis was done through flow cytometry. Further, Apoptosis was analyzed using Annexin V/PI staining, tunel assay and electron microscopic examination and verified using western blot analysis. In order to validate the in vitro results, in vivo analysis was performed using 4T1-syngeneic mouse model. KEY FINDINGS: In this study, we report that the dietary isoflavone genistein (GN) synergistically improved antineoplasticity of CC in breast cancer by arresting cells at G2/M phase culminating in ROS dependent apoptosis. The combination of CC plus GN caused dysregulation of Bax and Bcl-2 ratio inducing mitochondrial dysfunction, activation of Caspase-3/7, -9 and PARP cleavage. Further, combination significantly suppresses phosphorylation of PI3K/Akt/NF-κB, enhancing apoptosis. Additionally, combination markedly reduced tumor growth compared to CC and GN alone in mouse 4T1 breast tumor model. SIGNIFICANCE: Together, these studies suggest that GN represents a potential adjunct molecule whose role in CC induced apoptosis deserves attention.

Dietary isoflavone daidzein synergizes centchroman action via induction of apoptosis and inhibition of PI3K/Akt pathway in MCF-7/MDA MB-231 human breast cancer cells.

BACKGROUND: Despite advancements in the prognosis and management of breast cancer, it remains a major cause of mortality in women worldwide. Centchroman (CC), an oral contraceptive has been found to exhibit anti-cancer potential against a wide range of cancer including breast cancer. PURPOSE: The present study is intended to evaluate the ability of soy isoflavone Daidzein (DZ) in enhancing the efficacy of CC in Human Breast Cancer Cells (HBCCs). METHODS/STUDY DESIGN: Sulforhodamine B assay was employed to determine the cytotoxicity induced by 10 µM CC & 50 µM DZ separately and together in MCF-7/MDA MB-231 HBCCs and non-tumorigenic Human Mammary Epithelial Cells (HMECs) MCF-10A as a control. Combination Index (CI) analysis was executed using CompuSyn software. Further, apoptosis was assessed using Annexin V/PI, AO/PI staining and tunel assay. Cell cycle, reactive oxygen species generation and mitochondrial membrane potential alteration was determined using flow cytometry. Western blot analysis was performed to check the expression of respective proteins. RESULTS: The results suggest that the combination exerts elevated toxicity as compared to control and each drug per se without affecting HMECs MCF-10A. This therefore implies cancer cell specific action of CC plus DZ administered together. Additionally, combination index analysis suggests synergistic action of CC and DZ combination in HBCCs. Cell cycle analysis, Annexin V/PI staining, tunel assay and western blot analysis confirms the induction of apoptosis by combination in HBCCs. Interestingly, western blot analysis also revealed that the combination down-regulated the expression of proteins involved in cell survival i.e. PI3K, Akt and mTOR, suggesting inhibition of cell survival pathway. CONCLUSION: The results overall demonstrate that CC plus DZ has higher anticancer efficacy as compared to either drug alone. Hence, the combination of CC plus DZ may offer a novel strategy for the management of breast cancer.

Neem Seed Oil Induces Apoptosis in MCF-7 and MDA MB-231 Human Breast Cancer Cells

Background: In traditional Indian medicine, azadirachta indica (neem) is known for its wide range of medicinal properties. Various parts of neem tree including its fruit, seed, bark, leaves, and root have been shown to possess antiseptic, antiviral, antipyretic, anti-inflammatory, antiulcer, antimalarial, antifungal and anticancer activity. Materials and Methods: MCF-7 and MDA MB-231 cells were exposed to various concentrations of 2% ethanolic solution of NSO (1-30 µl/ml) and further processed for cell viability, cell cycle and apoptosis analysis. In addition, cells were analyzed for alteration in Mitochondrial Membrane Potential (MMP) and generation of Reactive Oxygen Species (ROS) using JC-1 and DCFDA staining respectively. Results: NSO give 50% inhibition at 10 µl/ml and 20 µl/ml concentration in MCF-7 and MDA MB-231 cells respectively and, arrests cells at G0/G1 phase in both the cell types. There was a significant alteration in mitochondrial membrane potential that leads to the generation of ROS and induction of apoptosis in NSO treated MCF-7 and MDA MB-231 cells. Conclusion: The results showed that NSO inhibits the growth of human breast cancer cells via induction of apoptosis and G1 phase arrest. Collectively these results suggest that NSO could potentially be used in the management of breast cancer.