Schisandrin B suppresses gastric cancer cell growth and enhances the efficacy of chemotherapy drug 5-FU in vitro and in vivo

He, Leye; Chen, Hao; Qi, Qinqin; Wu, Nan; Wang, Ying; Chen, Mengxia; Qian, Feng; Dong, Buyuan; Jin, Rong; Jiang, Lei

doi:10.1016/j.ejphar.2022.174823

Cited by 20 publications

(16 citation statements)

References 37 publications

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“…Natural plant compounds exhibit potential roles in enhancing the therapeutic effect of 5‐FU. For example, triptolide, 64 withaferin‐A, 65 kaempferol 66 in colorectal cancer; Docetaxel, 67 puerarin, 68 chrysin, 69 schisandrin B 70 in GC.…”

Section: Discussionmentioning

confidence: 99%

Morus alba derived Kuwanon‐A combined with 5‐fluorouracil reduce tumor progression via synergistic activation of GADD153 in gastric cancer

Thakur²,

Pan

et al. 2023

MedComm – Oncology

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Despite the application of conventional strategies including chemotherapy, radiotherapy, surgery, or immunotherapy, the mortality of gastric cancer (GC) patients remains high. Often, GC is not diagnosed until it has reached late stage, resulting in a missed surgical window. Therefore, a new therapeutic intervention for GC is necessary. Here, the combined application of Kuwanon‐A (KA) and 5‐fluorouracil (5‐FU) was evaluated for its potential to combat GC for the first time. To determine the anticancer activity of KA (from Morus alba) along with 5‐FU against GC, and their mechanism via GADD153, we examained anticancer potential of KA along with 5‐FU via in vitro assays with GC cells, namely MKN‐45, SGC‐7901, HGC‐27, and BGC‐823, and in vivo assays with mouse xenograft of GC. KA alone could induce G2/M phase arrest and apoptosis in GC cells by activating GADD153 through the PERK/elF2α/ATF4 and IRE1/XBP1 signaling pathways, suggesting a critical role of increased endoplasmic reticulum stress in KA‐induced apoptosis of GC cells. Moreover, the combination of KA and 5‐FU showed an enhanced synergistic anticancer effect against GC both in vitro and in vivo. Conclusively, the combination of KA and 5‐FU can act as an effective anticancer regimen in combating GC.

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Section: Discussionmentioning

confidence: 99%

Morus alba derived Kuwanon‐A combined with 5‐fluorouracil reduce tumor progression via synergistic activation of GADD153 in gastric cancer

Thakur²,

Pan

et al. 2023

MedComm – Oncology

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“…[ 47 ] Contrariwise to our results, a recent study reported that Sch‐B as a mono‐treatment or in combination with 5‐fluorouracil induced autophagy in gastric cancer cells. [ 49 ]…”

Section: Discussionmentioning

confidence: 99%

The potential effect of Schisandrin‐B combination with panitumumab in wild‐type and mutant colorectal cancer cell lines: Role of apoptosis and autophagy

Sana-Eldine

Abdelgawad

Kotb

et al. 2023

J Biochem & Molecular Tox

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Panitumumab is an approved monoclonal antibody for the treatment of colorectal cancer (CRC); however, mutations in EGFR signaling pathway resulted in poor response. Schisandrin-B (Sch-B) is a phytochemical that was suggested to protect against inflammation, oxidative stress, and cell proliferation. The present study aimed to investigate the potential effect of Sch-B on panitumumab-induced cytotoxicity in wild-type Caco-2, and mutant HCT-116 and HT-29 CRC cell lines, and the possible underlying mechanisms. CRC cell lines were treated with panitumumab, Sch-B, and their combination. The cytotoxic effect of drugs was determined by MTT assay. The apoptotic potential was assessed in-vitro by DNA fragmentation and caspase-3 activity. Additionally, autophagy was investigated via microscopic detection of autophagosomes and quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) measurement of Beclin-1, Rubicon, LC3-II, and Bcl-2 expression. The drug pair enhanced panitumumab cytotoxicity in all CRC cell lines where IC50 of panitumumab was decreased in Caco-2 cell line. Apoptosis was induced through caspase-3 activation, DNA fragmentation, and Bcl-2 downregulation. Caco-2 cell line treated with panitumumab showed stained acidic vesicular organelles, contrariwise, all cell lines treated with Sch-B or the drug pair displayed green fluorescence indicating the lack of autophagosomes. qRT-PCR revealed the downregulation of LC3-II in all CRC cell lines, Rubicon in mutant cell lines, andBeclin-1 in HT-29 cell line only. Sch-B at 6.5 µM promoted panitumumab-induced apoptotic cell death, in-vitro, via caspase-3 activation and Bcl-2 downregulation, rather than autophagic cell death. This novel combination therapy against CRC, allows the reduction of panitumumab dose to guard against its adverse effects.

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“…It has been found to exhibit multifarious biological activities, including neuroprotective, cardioprotective, antioxidant, hepatoprotective, anti-inflammatory and anti-cancer effects (Nasser et al, 2020). In particular, Sch B exhibits in vitro anti-proliferation and anti-metastasis effects, and in vivo anti-tumor activities against various cancers, such as liver, breast, gastric and cervical cancers (Dai et al, 2018; He et al, 2022; Yan et al, 2020). However, to date, little is known about the effects of Sch B on colorectal cancer (CRC).…”

Section: Introductionmentioning

confidence: 99%

“…Hence, development of an alternative therapeutic strategy with reduced side effects is highly demanded. Recently, Sch B has been reported to generate synergy with other chemotherapy drugs with attenuated side effects in gastric and cervical cancers (He et al, 2022; Yan et al, 2020). Our preliminary study showed that oral administration of Sch B in combination with 5-FU significantly reduced tumor volume in a xenograft CRC mouse model with significantly reduced diarrhea symptoms.…”

Section: Introductionmentioning

confidence: 99%

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Bioavailability of Schisandrin B and its effect on 5-Fluorouracil metabolism in a xenograft mouse model of colorectal cancer

Lee

Yang

et al. 2022

Preprint

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Schisandrin B (Sch-B) is a predominant bioactive lignan in the fruit of a traditional Chinese medicinal plant Schisandra Chinensis with widely reported anti-cancer properties. Using a xenograft mouse model of colorectal cancer (CRC), we showed potent anti-tumor effects of Sch-B and synergistic effects when co-treated with the chemotherapy drug, fluorouracil (5-FU). To explore the underlying anti-tumor mechanism of Sch-B, we first compared the bioavailability, metabolism and tissue distribution of Sch-B and its metabolites among healthy and tumor-bearing mice. To understand the drug-phytochemical interactions associated with the synergy between Sch-B and 5-FU, we examined their reciprocal influence on drug metabolism, tissue distribution, and multidrug resistance (MDR) gene expression in tumor-bearing mice. Using a targeted metabolomics approach, three Sch-B metabolites and two bioactive 5-FU metabolites were quantified and found to reach tumor tissue. Generally, Sch-B metabolites were present at higher levels in tumor-bearing than healthy mice, whereas 5-FU metabolite accumulation was remarkably higher in the co-treatment than 5-FU alone group. Moreover, MDR genes were significantly downregulated upon co-treatment, demonstrating the capacity of Sch-B to reverse MDR in chemotherapy. This study showed that Sch-B may serve as a promising adjuvant to chemotherapy drugs via favorably modulating drug metabolism and bioavailability, and attenuating MDR.

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Schisandrin B suppresses gastric cancer cell growth and enhances the efficacy of chemotherapy drug 5-FU in vitro and in vivo

Cited by 20 publications

References 37 publications

Morus alba derived Kuwanon‐A combined with 5‐fluorouracil reduce tumor progression via synergistic activation of GADD153 in gastric cancer

Morus alba derived Kuwanon‐A combined with 5‐fluorouracil reduce tumor progression via synergistic activation of GADD153 in gastric cancer

The potential effect of Schisandrin‐B combination with panitumumab in wild‐type and mutant colorectal cancer cell lines: Role of apoptosis and autophagy

Bioavailability of Schisandrin B and its effect on 5-Fluorouracil metabolism in a xenograft mouse model of colorectal cancer

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