Piperlongumine, a piper alkaloid targets Ras/PI3K/Akt/mTOR signaling axis to inhibit tumor cell growth and proliferation in DMH/DSS induced experimental colon cancer

Kumar, Sandeep; Agnihotri, Navneet

doi:10.1016/j.biopha.2018.10.182

Cited by 77 publications

(51 citation statements)

References 40 publications

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“…Oxaliplatin in combination with piperlongumine, a natural product constituent of the fruit of the Long pepper (Piper longum), has been shown to act synergically and induce CRC cell apoptosis via mitochondrial dysfunction and endoplasmic reticulum stress [128]. The mode of piperlongumine action in experimental colon cancer has recently been updated [129]. Our results showed that co-treatment of CRC cells with 5FU and Ganoderma Lucidum induces oxidative DNA damage in CRC cell lines.…”

Section: Possible Utilization Of Oxidative Dna Damage In Colorectal Cmentioning

confidence: 67%

Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients

Vodička

Urbanová

Makovický

et al. 2020

IJMS

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Oxidative stress with subsequent premutagenic oxidative DNA damage has been implicated in colorectal carcinogenesis. The repair of oxidative DNA damage is initiated by lesion-specific DNA glycosylases (hOGG1, NTH1, MUTYH). The direct evidence of the role of oxidative DNA damage and its repair is proven by hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome), where germline mutations cause loss-of-function in glycosylases of base excision repair, thus enabling the accumulation of oxidative DNA damage and leading to the adenoma-colorectal cancer transition. Unrepaired oxidative DNA damage often results in G:C>T:A mutations in tumor suppressor genes and proto-oncogenes and widespread occurrence of chromosomal copy-neutral loss of heterozygosity. However, the situation is more complicated in complex and heterogeneous disease, such as sporadic colorectal cancer. Here we summarized our current knowledge of the role of oxidative DNA damage and its repair on the onset, prognosis and treatment of sporadic colorectal cancer. Molecular and histological tumor heterogeneity was considered. Our study has also suggested an additional important source of oxidative DNA damage due to intestinal dysbiosis. The roles of base excision repair glycosylases (hOGG1, MUTYH) in tumor and adjacent mucosa tissues of colorectal cancer patients, particularly in the interplay with other factors (especially microenvironment), deserve further attention. Base excision repair characteristics determined in colorectal cancer tissues reflect, rather, a disease prognosis. Finally, we discuss the role of DNA repair in the treatment of colon cancer, since acquired or inherited defects in DNA repair pathways can be effectively used in therapy.

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Section: Possible Utilization Of Oxidative Dna Damage In Colorectal Cmentioning

confidence: 67%

Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients

Vodička

Urbanová

Makovický

et al. 2020

IJMS

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“…It might be because AOM administration was a week ahead of PL treatment, and PL can affect DSS-induced inflammation, but not AOM-induced mutagenesis and tumorigenesis. Similarly, a recent report has shown that PL could suppress tumor cell growth and proliferation in DMH/ DSS-induced experimental colon cancer by targeting Ras/PI3K/ Akt/mTOR signaling axis (Kumar and Agnihotri, 2019). PLinduced Cyclin D1 downregulation and tumor suppression in colorectal cancer cells by suppression of ERKs/Akt-mediated c-Fos expression (Gao et al, 2020).…”

Section: Discussionmentioning

confidence: 95%

Piperlongumine Alleviates Mouse Colitis and Colitis-Associated Colorectal Cancer

et al. 2020

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Colorectal cancer is one of the most common and lethal cancers in the world. An important causative factor of colorectal cancer is ulcerative colitis. In this study, we investigated the therapeutic effects of piperlongumine (PL) on the dextran sulfate sodium (DSS)-induced acute colitis and azoxymethane (AOM)/DSS-induced colorectal cancer mouse models. Our results showed that PL could inhibit the inflammation of DSS-induced mouse colitis and reduce the number of large neoplasms (diameter >2 mm) of AOM/DSS-induced mouse colorectal cancer by downregulation of proinflammatory cytokines cyclooxygenase-2 and interleukin-6 and epithelial-mesenchymal transition-related factors, β-catenin, and snail expressions, but fail to improve the colitis symptoms and to decrease the incidence of colonic neoplasms and the number of small neoplasms (diameter <2 mm). These data suggested that PL might be an effective agent in treating colitis and colorectal cancer.

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“…Our data showed that SLBZ-AP Many researchers confirmed that PI3K/Akt/mTOR signaling pathway is related to a few biological activities to affect cell proliferation, survival, and migration [7,8], especially to stimulate proliferation, survival, invasion/metastasis, and metabolic reprogramming and suppress autophagy, which is involved in possible mechanisms of oncogenic transformation [9]. PI3K/Akt/mTOR signaling pathway is commonly activated and suppression of its activation may inhibit cells proliferation and metastasis in cancers of the lung [10,11,50], colorectal [51,52], esophagus [53], breast [54][55][56], liver [57,58], and kidney [59,60], which has been considered a promising therapeutic target. Whether the PI3K/Akt/mTOR signaling pathway involved in SLBZ-AP affects BMLC was further explored in our study, results of which indicated that the mRNA and protein expression of AKT, mTOR, P70S6, and VEGF as well as protein expression of p-AKT, p-mTOR, p-P70S6, and VEGF was significantly increased in the marrow of tibia from BMLC mice.…”

Section: Discussionmentioning

confidence: 99%

Antinociceptive Effects of Shenling Baizhu through PI3K‐Akt‐mTOR Signaling Pathway in a Mouse Model of Bone Metastasis with Small‐Cell Lung Cancer

Feng

Han

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Shenling Baizhu additive powder (SLBZ-AP), a formulation of a variety of natural medicinal plants, has clinical efficacy in treating cancers in previous studies. We explored the effect of SLBZ-AP in bone metastasis of lung cancer (BMLC) mice, and the possible mechanism involved was further investigated in the present study. Mice model of BMLC was made and treated with SLBZ-AP. Pain behavioral tests were performed to explore the effect on BMLC-induced pain in mice. TUNEL staining was used to investigate apoptosis. The mRNA expression of markers in the PI3K/Akt/mTOR pathway was measured by qPCR, and protein expression was detected by western blotting and immunohistochemistry analysis. SLBZ-AP relieved BMLC-induced pain and prolonged animals’ survival, promoted cell apoptosis in the marrow from the tibia of BMLC mice, and inhibited mRNA and protein expression of AKT, mTOR, P70S6, and VEGF, as well as protein expression of p-AKT, p-mTOR, p-P70S6, and VEGF upregulation in the marrow of tibia induced by BMLC, an effect which was similar to rapamycin. Our results suggested that SLBZ-AP may have antinociceptive effect and prolong survival of BMLC mice at least partially by inhibiting cell proliferation and promoting apoptosis through the PI3K/Akt/mTOR signaling pathway. SLBZ-AP may be a potential candidate for BMLC therapy.

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Piperlongumine, a piper alkaloid targets Ras/PI3K/Akt/mTOR signaling axis to inhibit tumor cell growth and proliferation in DMH/DSS induced experimental colon cancer

Cited by 77 publications

References 40 publications

Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients

Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients

Piperlongumine Alleviates Mouse Colitis and Colitis-Associated Colorectal Cancer

Antinociceptive Effects of Shenling Baizhu through PI3K‐Akt‐mTOR Signaling Pathway in a Mouse Model of Bone Metastasis with Small‐Cell Lung Cancer

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