Maslinic Acid Enhances Immune Responses in Leukemic Mice Through Macrophage Phagocytosis and Natural Killer Cell Activities <i>In Vivo</i>

Lai, Kuang Chi; Peng, Shu‐Fen; Liu, Chia Chi; Huang, Jye Yu; Kuo, Jung Yu; Cheng, Ziyang; Wu, Rick Sai Chuen; Lin, Chyi-Chyang; Chen, Jr Kai; Chung, Jing Gung

doi:10.21873/invivo.11440

Cited by 14 publications

(9 citation statements)

References 41 publications

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“…↓IL-6, ↓TNF-α, ↑IL-10, [ 42 ] 5-week-old male BALB/c nude mice HCT116 xenograft model 10 mg/kg and 30 mg/kg day-1 Orally 17 days Suppressed the tumorigenesis, ↓p-mTOR, ↓p-4EBP1, ↓p70S6K,↑p- AMPK. [ 42 ] Leukemia 5-week-old male BALB/c mice WEHI-3 xenograft model 0, 8, 16, 32 mg/Kg Intraperitoneal injection 2 weeks Increase immune responses: enhanced macrophage phagocytosis and NK cell activities [ 80 ] Pancreatic cancer er 4–5 week-old athymic nu/nu male mice Panc-28 xenograft model 10, 50 mg/kg MA every 2 day Subcutaneous injected 36 days Suppressed pancreatic tumor growth, induced tumor apoptosis, and inhibited NF-B-regulated anti-apoptotic gene expression, such as Survivin and Bcl-xl. [ 112 ] Gallbladder cancer 6-week-old athymic nu/nu male mice EH-GB2 xenograft model 30 mg/kg MA every 2 days+GEM Subcutaneously injected 30 days Inhibitory tumor volume, and decreased NF-κB-regulated gene products expression.…”

Section: Anticancer Properties Of Maslinic Acidmentioning

confidence: 99%

The Anticancer Potential of Maslinic Acid and Its Derivatives: A Review

Yu¹,

Xie²,

Cao³

et al. 2021

DDDT

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Cancer is still an insurmountable problem for humans and critically attacking human health. In recent years, natural products have gained increasing attention in the field of anti-tumor due to their extensive sources and minimal side effects. Maslinic acid (MA), a pentacyclic triterpene acid mainly derived from the olive tree (Olea europaea L.) has been confirmed to possess great anti-cancer effects. This paper reviewed the inhibitory effect of MA and its derivatives on lung cancer, colon cancer, ovarian cancer, gastric cancer, lymphatic, leukemia, breast cancer, pancreatic cancer, melanoma, prostate cancer, renal cell carcinoma, gallbladder cancer, and bladder cancer, among others. MA inhibited the proliferation of various tumor cells and showed lower IC 50 values in melanoma 518A2 cells and gastric cancer MKN28 cells compared with other cell lines. A series of semi-synthetic derivatives obtained by modifying MA chemical structure have been shown to have high cytotoxicity to human tumor cell lines, but low cytotoxicity to nonmalignant cells, which is conducive to developing its potential as a chemotherapeutic agent. These studies suggest that MA derivatives have broad prospects in the development of antitumor therapeutics in the future and warrant further study.

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Section: Anticancer Properties Of Maslinic Acidmentioning

confidence: 99%

The Anticancer Potential of Maslinic Acid and Its Derivatives: A Review

Yu¹,

Xie²,

Cao³

et al. 2021

DDDT

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“…α-Phellandrene (α-PA) is a monoterpene compound, which is found in essential oils or extracts from natural plants, particularly in spices and herbs such as pine (1), ginger (2), dill (3) and peppermint (4). Previous studies have shown that α-PA has antidepressant (5), anti-inflammatory (6), immunoregulatory (7) and anticancer (8) effects. Our previous research demonstrated that α-PA can induce cell death by decreasing ATP levels (9) and trigger autophagy by affecting AKT/LC3II/mTOR signaling in human liver cancer cells (8).…”

Section: Introductionmentioning

confidence: 99%

α‑Phellandrene enhances the apoptosis of HT‑29 cells induced by 5‑fluorouracil by modulating the mitochondria‑dependent pathway

Susanto,

Hartajanie,

2024

Oncol Rep

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α-Phellandrene (α-PA), a natural constituent of herbs, inhibits cancer cell viability and proliferation. 5-Fluorouracil (5-FU) is a frequently utilized chemotherapeutic medicine for the treatment of colon cancer, which works by triggering cancer cell apoptosis. The present study examined how the combination of α-PA and 5-FU affects the suppression of human colon cancer cells by promoting apoptosis. The impact of this treatment on cell viability, apoptosis, and the expression levels of Bcl-2 family members, caspase family members and mitochondria-related molecules in HT-29 cells was assessed by the MTT assay, immunocytochemistry, western blotting and quantitative PCR. The combination of 5-FU and α-PA had a synergistic inhibitory effect on cell viability, as determined by assessing the combination index value. Bax protein expression levels were higher in the 50, 100 or 250 µM α-PA combined with 5-FU groups compared with those in the 5-FU alone group (P<0.05). By contrast, Bcl-2 protein expression levels and mitochondrial membrane potential (MMP, ΔΨm) were lower in the 100 or 250 µM α-PA combined with 5-FU groups than those in the 5-FU alone group (P<0.05). In addition, hexokinase-2 (HK-2) protein expression levels were lower in the 50, 100 or 250 µM α-PA combined with 5-FU groups than those in the 5-FU alone group (P<0.05). Compared with 5-FU alone, after HT-29 cells were treated with 50, 100 or 250 µM α-PA combined with 5-FU, the mRNA expression levels of extrinsic-induced apoptotic molecules, including caspase-8 and Bid, were higher (P<0.05). Treatment with 50, 100 or 250 µM α-PA combined with 5-FU also increased the mRNA expression levels of cytochrome c, caspase-9 and caspase-3, regulating intrinsic apoptosis (P<0.05). These results showed that α-PA and 5-FU had a synergistic effect on reducing the viability of human colon cancer HT-29 cells by inducing extrinsic and intrinsic apoptosis pathways. The mechanism by which apoptosis is induced may involve the intrinsic apoptosis pathway that activates the mitochondria-dependent pathway, including regulating the expression levels of Bcl-2 family members, including Bax, Bcl-2 and Bid, regulating MMP and HK-2 expression levels, and increasing the expression of caspase cascade molecules, including caspase-9 and caspase-3. In addition, it may involve the extrinsic apoptosis pathway that activates caspase-8 and caspase-3 leading to apoptosis.

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“…It has been reported to inhibit angiogenesis (Thakor et al, 2017 ) and cell migration and invasion in several cancers (Wei et al, 2019 ; Zhang et al, 2021 ). Moreover, MA can modulate the inflammatory response and potentiate the immune system action against cancer cells (Sánchez-Quesada et al, 2015 ; Lai et al, 2019 ). Sánchez-Quesada et al reported that MA promoted the in vitro production of pro-inflammatory and macrophage recruitment-related cytokines in macrophages and that it favored their differentiation to M1 state, which is the phenotype involved in the immune defense against cancer cells (Sánchez-Quesada et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Solid lipid nanoparticles to improve bioaccessibility and permeability of orally administered maslinic acid

et al. 2022

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Maslinic acid (MA) is a plant-derived, low water-soluble compound with antitumor activity. We have formulated MA in the form of solid lipid nanoparticles (SLNs) with three different shell compositions: Poloxamer 407 (PMA), dicarboxylic acid-Poloxamer 407 (PCMA), and HA-coated PCMA (PCMA-HA). These SLNs improved the solubility of MA up to 7.5 mg/mL, are stable in a wide range of pH, and increase the bioaccessibility of MA after in vitro gastrointestinal (GI) digestion. Gastrointestinal digested SLNs afforded MA delivery across in vitro gut barrier models (21 days old Caco-2 and mucus-producing Caco-2/HT29-MTX co-cultures). The cellular fraction of Caco-2/HT29-MTX co-cultures retained more MA from GI digested PCMA-HA than the Caco-2 monolayers. The concentration of MA reached in the basolateral chamber inhibited growth of pancreatic cancer cells, BxPC3. Finally, confocal microscopy images provided evidence that Nile Red incorporated in MA SLNs was capable of crossing Caco-2 monolayers to be taken up by basolaterally located BxPC3 cells. We have demonstrated that SLNs can be used as nanocarriers of hydrophobic antitumor compounds and that these SLNs are suitable for oral consumption and delivery of the bioactive across the gut barrier.

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Maslinic Acid Enhances Immune Responses in Leukemic Mice Through Macrophage Phagocytosis and Natural Killer Cell Activities In Vivo

Cited by 14 publications

References 41 publications

The Anticancer Potential of Maslinic Acid and Its Derivatives: A Review

The Anticancer Potential of Maslinic Acid and Its Derivatives: A Review

α‑Phellandrene enhances the apoptosis of HT‑29 cells induced by 5‑fluorouracil by modulating the mitochondria‑dependent pathway

Solid lipid nanoparticles to improve bioaccessibility and permeability of orally administered maslinic acid

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