Ursolic acid induces apoptosis and anoikis in colorectal carcinoma RKO cells

Zheng, Jia-Lu; Wang, Shuangshuang; Shen, Ke‐Ping; Chen, Lei; Pan, Xiao; Chen, Jinfang; An, Hong‐Mei; Hu, Bing

doi:10.1186/s12906-021-03232-2

Cited by 16 publications

(18 citation statements)

References 23 publications

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“…However, all six cell lines treated with EPI showed evident bright blue, nuclear fragmentation, chromatin condensation, and formation of apoptotic bodies (Figure 4). Consistent with the results from the apoptosis assay, morphological analysis of the cancer cells after the treatment of H. leucospilota protein showed bright blue, nuclear fragmentation, and chromatin condensation, clear evidence suggesting apoptosis [28]; in contrast, morphological analysis did not show obvious morphological changes in any of the H. leucospilota protein treated normal cells. However, all six cell lines treated with EPI showed evident bright blue, nuclear fragmentation, chromatin condensation, and formation of apoptotic bodies (Figure 4).…”

Section: Effects Of H Leucospilota Protein Treatment On Inducing Cell...supporting

confidence: 82%

Cancer Cell Inhibiting Sea Cucumber (Holothuria leucospilota) Protein as a Novel Anti-Cancer Drug

Guo

Mao

et al. 2022

Nutrients

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Cancer remains the primary cause of death worldwide. To develop less toxic anti-cancer drugs to relieve the suffering and improve the survival of cancer patients is the major focus in the anti-cancer field. To this end, marine creatures are being extensively studied for their anti-cancer effects, since extracts from at least 10% of the marine organisms have been shown to possess anti-tumor activities. As a classic Chinese traditional medicine, sea cucumbers and compounds extracted from the sea cucumbers, such as polysaccharides and saponins, have recently been shown to exhibit anti-cancer, anti-inflammatory, and anti-oxidant effects. Holothuria leucospilota (H. leucospilota) is a tropical edible sea cucumber species that has been successfully cultivated and farmed in large scales, providing a readily available source of raw materials to support the development of novel marine anti-cancer drugs. However, very few studies have so far been performed on the biological activities of H. leucospilota. In this study, we first investigated the anti-cancer effect of H. leucospilota protein on three cancer cell lines (i.e., HepG2, A549, Panc02) and three normal cell lines (NIH-3T3, HaCaT, 16HBE). Our data showed that H. leucospilota protein decreased the cell viabilities of HepG2, A549, HaCaT, 16HBE in a concentration-dependent manner, while Panc02 and NIH-3T3 in a time- and concentration-dependent manner. We also found that the inhibitory effect of H. leucospilota protein (≥10 μg/mL) on cell viability is near or even superior to EPI, a clinical chemotherapeutic agent. In addition, our data also demonstrated that H. leucospilota protein significantly affected the cell cycle and induced apoptosis in the three cancer cell lines investigated; in comparison, it showed no effects on the normal cell lines (i.e., NIH-3T3, HaCaT and 16HBE). Finally, our results also showed that H. leucospilota protein exhibited the excellent performance in inhibiting cell immigrations. In conclusion, H. leucospilota protein targeted the cancer cell cycles and induced cancer cell apoptosis; its superiority to inhibit cancer cell migration compared with EPI, shows the potential as a promising anti-cancer drug.

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Section: Effects Of H Leucospilota Protein Treatment On Inducing Cell...supporting

confidence: 82%

Cancer Cell Inhibiting Sea Cucumber (Holothuria leucospilota) Protein as a Novel Anti-Cancer Drug

Guo

Mao

et al. 2022

Nutrients

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“…Numerous treatments with natural products, such as herbal compounds, have been evaluated for their ability to induce cell apoptosis in crc (106)(107)(108)(109). Previous studies have assessed whether cell apoptosis is induced by UA in cancer, such as CRC and breast and esophageal cancer, via different mechanisms (27,110,111). The present study demonstrated that combined UA + DOX treatment promoted crc cell late apoptosis and increased the sub-G 1 apoptotic fraction as assessed by FITC/PI staining and flow cytometry.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway

Meng

Nguyen

et al. 2022

Mol Med Rep

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colorectal cancer (crc) is one of the deadliest malignant tumors worldwide and its prevalence is increasing in South Korea. The efficacy of combined treatment with natural product-derived and chemotherapy agents including curcumin combined with 5-fluorouracil, resveratrol combined with cisplatin and epigallocatechin-3-gallate (EGCG) combined with cisplatin in preventing cancer progression and killing cancer cells has emerged. The akt and Hippo signaling pathways serve a key role in colorectal tumor growth; however, the exact role of the crosstalk between Akt and Hippo signaling pathways in CRC remains poorly elucidated. The combined effect of ua and doX on the cell proliferation, apoptosis, migration and cell cycle of CRC cells were investigated by performing Cell proliferation assay, a soft agar colony formation assay, flow cytometry, wound healing assay and western blotting assay. Subsequently, the expression of AKT and Hippo signaling pathway-associated proteins were also assessed by western blot assay. Moreover, a xenograft nude mouse model was constructed to verify the effects of UA and doX on the tumorigenesis of HcT116 cell in vivo. The present study reported that ursolic acid (UA) strongly enhanced the antitumor action of doxorubicin (DOX) via blocking the akt/glycogen synthase kinase-3β (Gsk3β) signaling pathway and activating tumor-suppressive Hippo signaling (mammalian Ste20-like kinase 1 and 2, salvador family WW domain containing protein 1 and MOB kinase activator 1), thereby downregulating downstream effector yes-associated protein 1 (Yap) and connective tissue growth factor (cTGF) protein expression levels in CRC cells. Furthermore, The PI3K inhibitor LY294002 further suppressed Akt activity and enhance the function of Hippo pathway-associated proteins in DOX + UA treated cells; this effect led to subsequent oncogenic Yap and CTGF inhibition following combined treatment, whereas akt activator Sc79 exerted an opposite effect in cTGF expression. In vivo, treatment with UA combined with DOX markedly suppressed the progression of CRC without any toxic effects on a xenograft mouse model by disrupting Akt signaling and activating the Hippo signaling pathway. These results demonstrated that UA and DOX treatment successfully induced akt/Gsk3β inactivation via Hippo signaling pathway activation to promote Yap degradation, resulting in the inhibition of colorectal tumorigenesis. In conclusion, these findings suggested that combination therapy with UA and DOX may be more effective than DOX alone. UA may be a novel anticancer strategy and could be considered for investigation as a complementary chemotherapy agent in the future.

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“…cytometry, UA and 5-FU were found to arrest the cell cycle at the G0/G1 phase, with a diminished proportion in the S phase (Figure 3A), consistent with another report. 21 Subsequently, the influence of UA on cell cycle-related gene expression was appraised. Intriguingly, UA concentration-dependently diminished mRNA abundance in c-Myc and cyclin D1 of SW620 cells (Figure 3B), consolidated by the western blotting, whose data suggested that UA also concentration-dependently mitigated protein expressions of c-Myc and cyclin D1 in SW620 cells (Figure 3C).…”

Section: Ursolic Acid Inhibits the Malignant Phenotype Of Human Crc C...mentioning

confidence: 99%

Ursolic Acid Suppresses Colorectal Cancer by Down-Regulation of Wnt/β-Catenin Signaling Pathway Activity

Zhao

Tang

Qiu

et al. 2023

J. Agric. Food Chem.

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Overwhelming evidence points to an abnormally active Wnt/β-catenin signaling as a key player in colorectal cancer (CRC) pathogenesis. Ursolic acid (UA) is a pentacyclic triterpenoid that has been found in a broad variety of fruits, spices, and medicinal plants. UA has been shown to have potent bioactivity against a variety of cancers, including CRC, with the action mechanism obscure. Our study tried to learn more about the efficacy of UA on CRC and its functional mechanism amid the Wnt/β-catenin signaling cascade. We determined the efficacy of UA on CRC SW620 cells with respect to the proliferation, migration, clonality, apoptosis, cell cycle, and Wnt/β-catenin signaling cascade, with assessment of the effect of UA on normal colonic NCM460 cells. Also, the effects of UA on the tumor development, apoptosis, cell cycle, and Wnt/β-catenin signaling axis were evaluated after a subcutaneous SW620 xenograft tumor model was established in mice. In this work, we showed that UA drastically suppressed proliferation, migration, and clonality; induced apoptosis; and arrested the cell cycle at the G0/G1 phase of SW620 cells, without the influence on NCM460 cells, accompanied by weakened activity of the Wnt/β-catenin signaling pathway. Besides, UA markedly deterred the growth of the xenograft tumor, ameliorated pathological features, triggered apoptosis, and arrested the cell cycle in xenograft CRC tissue, by lessening the Wnt/β-catenin signaling cascade. Overall, UA may inhibit the malignant phenotype, induce apoptosis, and arrest the cell cycle of CRC, potentially by attenuating the Wnt/β-catenin signaling axis, providing insights into the mechanism for the potency of UA on CRC.

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Ursolic acid induces apoptosis and anoikis in colorectal carcinoma RKO cells

Cited by 16 publications

References 23 publications

Cancer Cell Inhibiting Sea Cucumber (Holothuria leucospilota) Protein as a Novel Anti-Cancer Drug

Cancer Cell Inhibiting Sea Cucumber (Holothuria leucospilota) Protein as a Novel Anti-Cancer Drug

Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway

Ursolic Acid Suppresses Colorectal Cancer by Down-Regulation of Wnt/β-Catenin Signaling Pathway Activity

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