Residual powders from Shochu distillation remnants induce apoptosis in human hepatoma cells via the caspase-independent pathway

Ohgidani, Masahiro; Komizu, Yuji; Goto, Kōichi; Ueoka, Ryuichi

doi:10.1016/j.jbiosc.2012.02.026

Cited by 5 publications

(6 citation statements)

References 21 publications

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“…These results strongly suggest that AMF-induced apoptosis does not depend only on caspase activation. Similar results have been shown in various cell lines using, for example, magnolol (a small-molecule hydroxylated biphenol) [ 17 ], alpha hydroxy acid [ 18 ] and distillation remnants from Japanese liquor [ 19 ]. Additionally, it has been shown that chemotherapeutics like topoisomerase II inhibitors, kinase inhibitors and proteasome inhibitors may induce apoptosis also by a caspase independent pathway possibly depending on Panx1 expression, which is a structural component in gap junctions and hemichannels an involved in nucleotide release during chemotherapeutic-drug induced apoptosis [ 20 ].…”

Section: Resultssupporting

confidence: 81%

Akacid Medical Formulation Induces Apoptosis in Myeloid and Lymphatic Leukemic Cell Lines In Vitro and In Vivo

et al. 2015

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Akacid medical formulation (AMF) is an oligoguanidine that exerts biocidal activity against airborne and surface microorganisms including bacteria, viruses, fungi, and molds, while showing relatively low toxicity to humans. We have previously shown that AMF exerts antiproliferative effects on a variety of solid tumor cell lines. In this study we raised the question whether AMF could also substantially inhibit cell growth or induce apoptosis in cell lines derived from hematologic malignancies such as leukemia or lymphoma. We found that AMF has antiproliferative effects on various hematologic cell lines derived from human leukemia and lymphoma. Additionally, we show that AMF induces apoptosis in leukemia cell lines not only via the extrinsic and intrinsic pathway, but also in a caspase-independent manner. This effect was found also in G0-arrested cells. Finally, in our animal experiments utilizing male nu/nu Balb/c mice we found a significant growth retardation, which was immunohistochemically associated with a significantly lower number of KI67-positive cells and caspase-3 induction in AMF-treated mice.

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Section: Resultssupporting

confidence: 81%

Akacid Medical Formulation Induces Apoptosis in Myeloid and Lymphatic Leukemic Cell Lines In Vitro and In Vivo

et al. 2015

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“…Apoptosis can be induced via caspase-dependent and caspase-independent pathways (44,45). Vitamin C treatment can induce apoptosis of breast cancer cells and lung cancer cells via the caspase-independent pathway (36,55,56).…”

Section: Discussionmentioning

confidence: 99%

“…4, nuclear condensation and DNA fragmentation were observed in MTX-treated and MTX plus vitamin C-treated groups. Apoptosis can be initiated by caspase-dependent and caspase-independent pathways (44,45). Therefore, caspase-3 activation was examined by western blotting.…”

Section: Mtx-treatment and Combined Mtx Plus Vitamin C Treatment Indumentioning

confidence: 99%

Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways

Liu

et al. 2017

Oncology Reports

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Methotrexate (MTX) is widely used as both an anticancer and anti-rheumatoid arthritis drug. Although MTX has been used to inhibit the growth of many cancer cells, it cannot effectively inhibit growth of triple-negative breast cancer cells (TNBC cells). Vitamin C is an antioxidant that can prevent oxidative stress. In addition, vitamin C has been applied as adjunct treatment for growth inhibition of cancer cells. Recent studies indicated that combined treatment with vitamin C and MTX may inhibit MCF-7 and MDA-MB-231 breast cancer cell growth through G2/M elongation. However, the mechanisms remain unknown. The aim of the present study was to determine whether combined treatment with low-dose vitamin C and MTX inhibits TNBC cell growth and to investigate the mechanisms of vitamin C/MTX-induced cytotoxicity. Neither low-dose vitamin C alone nor MTX alone inhibited TNBC cell growth. However, combined low-dose vitamin C and MTX had synergistic anti-proliferative/cytotoxic effects on TNBC cells. In addition, co-treatment increased H2O2 levels and activated both caspase-3 and p38 cell death pathways.

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“…Many studies have demonstrated that MTX induces cancer cell death via apoptotic death pathways (10–14). Apoptotic death pathways can be divided into caspase-dependent and caspase-independent cascades (15,16). Concerning the MTX-induced apoptotic pathways, most studies have shown that MTX induces apoptosis via caspase-dependent cascades in many cancer cell lines (17–21).…”

Section: Introductionmentioning

confidence: 99%

Vitamin C enhances anticancer activity in methotrexate-treated Hep3B hepatocellular carcinoma cells

et al. 2014

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Methotrexate (MTX) has been widely used for rheumatoid arthritis therapy for a long time. MTX is also used as an anticancer drug for various tumors. However, many studies have shown that high-dose MTX treatment for cancer therapy may cause liver and renal damage. Alhough the mechanisms involved in MTX-induced liver and renal damage require further research, many studies have indicated that MTX-induced cytotoxicity is associated with increases in oxidative stress and caspase activation. In order to reduce MTX-induced side-effects and increase anticancer efficiency, currently, combination treatments of low-dose MTX and other anticancer drugs are considered and applied for various tumor treatments. The present study showed that MTX induces increases in H2O2 levels and caspase-9/-3 activation leading to cell death in hepatocellular carcinoma Hep3B cells. Importantly, this study is the first to demonstrate that vitamin C can efficiently aid low-dose MTX in inducing cell death in Hep3B cells. Therefore, the present study provides a possible powerful therapeutic method for tumors using a combined treatment of vitamin C and low-dose MTX.

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Residual powders from Shochu distillation remnants induce apoptosis in human hepatoma cells via the caspase-independent pathway

Cited by 5 publications

References 21 publications

Akacid Medical Formulation Induces Apoptosis in Myeloid and Lymphatic Leukemic Cell Lines In Vitro and In Vivo

Akacid Medical Formulation Induces Apoptosis in Myeloid and Lymphatic Leukemic Cell Lines In Vitro and In Vivo

Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways

Vitamin C enhances anticancer activity in methotrexate-treated Hep3B hepatocellular carcinoma cells

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